发明内容 SUMMARY

本发明涉及式I的化合物、它们的N-氧化物和农业上适用的盐 Suitable salts of the compounds of formula I of the present invention, their N- oxides and Agriculture 其中A和B独立地为O或S；R1为H、C1-C6烷基、C2-C6烷氧羰基或C2-C6烷基羰基；R2为H或C1-C6烷基；R3为H；C1-C6烷基、C2-C6链烯基、C2-C6炔基或C3-C6环烷基，它们各自任选地被一个或多个选自以下的取代基取代：卤素、CN、NO2、羟基、C1-C4烷基、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C2-C6烷氧羰基、C2-C6烷基羰基、C3-C6三烷基甲硅烷基、苯基、苯氧基、5元杂芳环和6元杂芳环；苯基、苯氧基、5元杂芳环和6元杂芳环各自任选地被1至3个独立地选自以下的取代基取代：C1-C4烷基、C2-C4链烯基、C2-C4炔基、C3-C6环烷基、C1-C4卤烷基、C2-C4卤链烯基、C2-C4卤炔基、C3-C6卤环烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C4-C8(烷基)(环烷基)氨基、C2-C4烷基羰基、C2-C6烷氧羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基和C3-C6三烷基甲硅烷基；C1-C4烷氧基；C1-C4烷基氨基；C2-C8二烷基氨基；C3-C6环烷基氨基；C2-C6烷氧羰基或C2-C6烷基羰基；R4为H、C1-C6烷基、C2-C6链烯基、C2-C6炔基、C3-C6环烷基、C1-C6卤烷基、CN、卤素、C1-C4烷氧基、C1-C4卤烷氧基或NO2；R5为H、C1-C6烷基、C1-C6卤烷基、C1-C4烷氧基烷基、C1-C4羟基烷基、C(O)R10、CO2R10、C(O)NR10R11、卤素、C1-C4烷氧基、C1-C4卤烷氧基、NR10R11、N(R11)C(O)R10、N(R11)CO2R10或S(O)nR12；R6为H、C1-C6烷基、C1-C6卤烷基、卤素、CN、C1-C4烷氧基或C1-C4卤烷氧基；R7为C1-C6烷基、C2-C6链烯基、C2-C6炔基、C3-C6环烷基、C1-C6卤烷基、C2-C6卤链烯基、C2-C6卤炔基或C3-C6卤环烷基；或R7为苯基环、苄基环、5或6元杂芳环、萘基环体系或8、9或10元稠和杂双环体系，每个环或环体系任选地被1至3个独立地选自R9的取代基取代；R8为H、C1-C6烷基、C1-C6卤烷基、卤素、C1-C4烷氧基或C1-C4卤烷氧基；每个R9独立地为C1-C4烷基、C2-C4链烯基、C2-C4炔基、C3-C6环烷基、C1-C4卤烷基、C2-C4卤链烯基、C2-C4卤炔基、C3-C6卤环烷基、卤素、CN、NO2、C1-C4烷氧基、C1-C4卤烷氧基、C1-C4烷硫基、C1-C4烷基亚磺酰基、C1-C4烷基磺酰基、C1-C4烷基氨基、C2-C8二烷基氨基、C3-C6环烷基氨基、C4-C8(烷基)(环烷基)氨基、C2-C4烷基羰基、C2-C6烷氧羰基、C2-C6烷基氨基羰基、C3-C8二烷基氨基羰基或C3-C6三烷基甲硅烷基； Wherein A and B are independently O or S; R1 is H, C1-C6 alkyl, C2-C6 alkoxycarbonyl or C2-C6 alkylcarbonyl group; R2 is H or C1-C6 alkyl; R3 is H; C1 -C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl, each optionally substituted with one or more substituents selected from the following substituents: halogen, CN, NO2, hydroxy , C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C2-C6 alkoxy oxycarbonyl group, C2-C6 alkylcarbonyl, C3-C6 trialkylsilyl, phenyl, phenoxy, 5-membered heteroaryl ring and a 6-membered heteroaromatic ring; phenyl, phenoxy, 5-membered heteroaryl ring and a 6-membered heteroaromatic ring optionally substituted with 1 to 3 substituents independently selected from the following substituents: C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl group, C1-C4 haloalkyl, C2-C4 halo alkenyl, C2-C4 haloalkynyl group, C3-C6 halocycloalkyl, halogen, CN, NO2, C1-C4 alkoxy, C1-C4 haloalkoxy alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkyl group, C4-C8 (alkyl) (cycloalkyl) amino, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3-C8 dialkylaminocarbonyl group, and C3-C6 trioxane silyl; C1-C4 alkoxy; C1-C4 alkylamino; C2-C8 dialkylamino group; C3-C6 cycloalkylamino group; C2-C6 alkoxycarbonyl or C2-C6 alkylcarbonyl group; R4 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, CN, halogen, C1-C4 alkoxy, C1-C4 haloalkoxy or NO2; R5 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C4 alkoxyalkyl, C1-C4 hydroxyalkyl, C (O) R10, CO2R10, C ( O) NR10R11, halogen, C1-C4 alkoxy, C1-C4 haloalkoxy, NR10R11, N (R11) C (O) R10, N (R11) CO2R10 or S (O) nR12; R6 is H, C1 -C6 alkyl, C1-C6 haloalkyl, halogen, CN, C1-C4 alkoxy or C1-C4 haloalkoxy; R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl group, C3-C6 cycloalkyl, C1-C6 haloalkyl, C2-C6 halo alkenyl, C2-C6 alkynyl or halo C3-C6 cycloalkyl, halogen; or R7 is a phenyl ring, a benzyl ring, 5 or 6-membered heteroaromatic ring, naphthyl ring system or a 8, 9 or 10-membered fused bicyclic heteroaryl system, each ring or ring system is optionally substituted independently selected from 1-3 R9 substituents; R8 is H, C1-C6 alkyl, C1-C6 haloalkyl, halogen, C1-C4 alkoxy or C1-C4 haloalkoxy; each R9 is independently C1-C4 alkyl, C2-C4 alkenyl group, C2-C4 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C2-C4 halo alkenyl, C2-C4 haloalkynyl group, C3-C6 halocycloalkyl, halogen, CN, NO2 , C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkylamino, C2-C8 dialkylamino, C3-C6 cycloalkylamino, C4-C8 (alkyl) (cycloalkyl) amino, C2-C4 alkylcarbonyl, C2-C6 alkoxycarbonyl, C2-C6 alkylaminocarbonyl, C3 -C8 dialkylaminocarbonyl group or a C3-C6 trialkylsilyl group;

R10为H、C1-C4烷基或C1-C4卤烷基；R11为H或C1-C4烷基；R12为C1-C4烷基或C1-C4卤烷基；且n为0、1或2。 R10 is H, C1-C4 alkyl or C1-C4 haloalkyl; R11 is H or C1-C4 alkyl; R12 is C1-C4 alkyl or C1-C4 haloalkyl; and n is 0, 1 or 2 .

本发明提供保护繁殖体或从其生长的植物免受无脊椎害虫侵害的方法。 The present invention provides protection propagules or growing plants from invertebrate pests method thereof. 该方法包括使该繁殖体或该繁殖体的场所与生物有效量的式I的化合物、其N-氧化物或其农业上适用的盐接触。 Which comprises reacting a compound of formula I and biological properties of the propagule or the propagules effective amount, suitable salt thereof N- oxide thereof or an agriculturally.

本发明还提供一种繁殖体，其包含生物有效量的式I的化合物、其N-氧化物或其农业上适用的盐。 The present invention also provides a propagule, a biologically effective amount of a compound of formula I, which comprises, salts of N- oxide thereof or an agriculturally.

本发明进一步提供一种繁殖体，其与生物有效量的式I的化合物、其N-氧化物或其农业上适用的盐接触。 The present invention further provides a propagule, with a biologically effective amount of a compound of formula I, suitable salt thereof N- oxide thereof or an agriculturally.

本发明还进一步提供用于涂覆繁殖体的无脊椎害虫防治组合物，其包含生物有效量的式I的化合物、其N-氧化物或其农业上适用的盐，以及成膜剂或粘合剂。 The present invention still further provides an invertebrate pest control composition for coating a propagule, the biologically effective amount of a compound of formula I, which comprises, on its N- oxides or agriculturally suitable salt thereof, and a film former or adhesive agent.

具体实施方案在本发明的说明书和权利要求书中所提到的术语“繁殖体”指种子或可再生的植物部分。 Specific embodiments In the description and claims of the present invention requires mentioned term "propagule" means a seed or a regenerable plant part. 术语“可再生的植物部分”指除种子外的植物部分，当将该植物部分置于园艺或农业生长介质中时，整个植物可以生长或再生，所述生长介质如湿润的土壤、泥煤苔、沙子、蛭石、珍珠岩、矿毛绝缘纤维、玻璃丝、椰子壳纤维、椤纤维等，或者甚至是完全液态的介质如水。 The term "regenerable plant part" means, except the seeds of the plant parts, when the horticultural or agricultural plant growth medium when the part is placed, the whole plant may be grown or regenerated, the growth medium, such as moist soil, peat moss , sand, vermiculite, perlite, mineral wool insulation fibers, fiberglass, coconut husk fiber, fern fiber and the like, or even a completely liquid medium such as water. 可再生的植物部分通常包括地下芽植物品种如马铃薯、甘薯、山药、洋葱、大丽花、郁金香、水仙等的根茎、块茎、鳞茎和球茎。 Renewable plant parts usually include underground bud plant species such as potatoes, sweet potatoes, yams, onions, dahlias, tulips, daffodils and other roots, tubers, bulbs and corms. 可再生的植物部分包括被分开(例如切割)以保持它们长成新植物的能力的植物部分。 Regenerable plant parts include a separate (e.g., cut) to maintain the plant part of their ability to grow into a new plant. 因此可再生的植物部分包括根茎、块茎、鳞茎和球茎的活的分割部分，它们保留有分生组织，如芽眼。 Therefore, renewable plant parts including live split part rhizomes, tubers, bulbs and corms, and they retain the partakers Health Organization, such as the buds. 可再生的植物部分还可以包括其它植物部分，如切割或分离的茎和叶，利用园艺或农业生长介质能够从它们生长一些植物品种。 Regenerable plant parts can also include other plant parts such as cut or separated stems and leaves, agricultural or horticultural use of the growth medium of some varieties of plants can be grown from them. 在本发明的说明书和权利要求书中所提及的，除非另外指明的术语“种子”包括未发芽的种子和外种皮(种子包被)仍部分包裹着显露的幼芽和根的发芽的种子。 In the description and claims of the invention mentioned requirements, unless otherwise indicated, the term "seed" including non-germinated seeds and testa (seed coat) still partially wrapped revealed shoots and roots sprouting seed.

在上面的陈述中，术语“烷基”，单独使用或在组合词，如“烷硫基”或“卤烷基”中使用，包括直链或支链烷基，如甲基、乙基、正丙基、异丙基或不同的丁基、戊基或己基异构体。 In the above statement, the term "alkyl", alone or in compound words such as "alkylthio" or "haloalkyl", including straight-chain or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl or the different butyl, pentyl or hexyl isomers. “链烯基”包括直链或支链烯，如1-丙稀基、2-丙烯基和不同的丁烯基、戊烯基和己烯基异构体。 "Alkenyl" includes straight-chain or branched alkenyl, such as 1-propenyl, 2-propenyl and the different butenyl, pentenyl and hexenyl isomers. “链烯基”也包括多烯，如1，2-丙二烯基和2，4-己二烯基。 "Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-cyclohexadienyl. “炔基”包括直链或支链炔，如1-丙炔基、2-丙炔基和不同的丁炔基、戊炔基和己炔基异构体。 "Alkynyl" includes straight-chain or branched alkynyl, such as 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. “炔基”也可以包括含有多个三键的基团，如2，5-己二炔基。 "Alkynyl" can also include a plurality of triple bonds containing groups, such as 2,5-hexadiynyl. “烷氧基”包括，例如甲氧基、乙氧基、正丙氧基、异丙氧基和不同的丁氧基、戊氧基和己氧基异构体。 "Alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy and the different butoxy, pentoxy and hexyloxy isomers. “烷氧基烷基”指烷基上有烷氧基取代。 "Alkoxyalkyl" refers to an alkoxy group substituted on the alkyl. “烷氧基烷基”的实例包括CH3OCH2、CH3OCH2CH2、CH3CH2OCH2、CH3CH2CH2CH2OCH2和CH3CH2OCH2CH2。 Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. “烷硫基”包括支链和直链烷硫基，如甲硫基、乙硫基和不同的丙硫基、丁硫基、戊硫基和己硫基异构体。 "Alkylthio" includes both branched and straight-chain alkylthio, such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. “环烷基”包括，例如，环丙基、环丁基、环戊基和环己基。 "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

术语“杂环”或“杂环体系”指环或环体系，其中至少一个环原子不是碳，并含有1-4个独立地选自氮、氧和硫的杂原子，条件是每个杂环含有不多于4个氮原子，不多于2个氧和不多于2个硫原子。 The term "heterocycle" or "heterocyclic ring system" ring or ring system, wherein at least one ring atom is not carbon, and containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur atoms, provided that each heterocyclic ring contains no more than 4 nitrogen atoms, not more than 2 oxygen and no more than two sulfur atoms. 杂环可以通过取代任何存在的碳或氮上的氢而与所述的碳或氮相连。 Heterocyclic ring may be connected to the carbon or nitrogen by substitution of any hydrogen on the presence of carbon or nitrogen. 术语“芳环体系”指完全不饱和的碳环和杂环，其中该多环体系的至少一个环是芳香性的(这里芳香性指该环体系满足Hückel规则)。 The term "aromatic ring system" refers to a fully unsaturated carbocyclic and heterocyclic, polycyclic ring systems wherein the at least one ring is aromatic (where aromatic ring system refers to satisfy the Hückel rule). 术语“杂芳环”指完全芳香性的环，其中至少一个环原子不是碳，并含有1-4个独立地选自氮、氧和硫的杂原子，条件是每个杂环含有不多于4个氮，不多于2个氧和不多于2个硫(这里芳香性指满足Hückel规则)。 The term "heteroaryl ring" refers to a fully aromatic ring, wherein at least one ring atom is not carbon, and containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur atoms, provided that each heterocyclic ring contains no more than 4 nitrogen, no more than 2 oxygen and no more than two sulfur (herein refers to aromatic meet Hückel rule). 杂环可以通过取代任何存在的碳或氮上的氢而与所述的碳或氮相连。 Heterocyclic ring may be connected to the carbon or nitrogen by substitution of any hydrogen on the presence of carbon or nitrogen. 术语“芳香性杂环体系”包括完全芳香性的杂环和其中多环体系的至少一个环是芳香性的杂环(这里芳香性指满足Hückel规则)。 The term "aromatic heterocyclic ring system" includes fully aromatic polycyclic heterocyclic system and wherein the at least one heterocyclic ring is aromatic (where aromatic refers to meet Hückel rule). 术语“稠杂双环体系”包括由两个稠合的环组成的环体系，其中至少一个环原子不是碳，并且如上所定义，可以是芳香性的或非芳香性的。 The term "heteroaryl fused bicyclic ring system" includes two fused rings of the ring system, wherein at least one ring atom is not carbon, and are as defined above, may be aromatic or non-aromatic in nature.

术语“卤素”，单独使用或在组合词，如“卤烷基”中使用，包括氟、氯、溴或碘。 The term "halogen", employed alone or in compound words such as "haloalkyl", including fluorine, chlorine, bromine or iodine. 而且，当用于如“卤烷基”的组合词时，所述的烷基可以被卤原子部分或完全取代，所述卤原子可以相同或不同。 Furthermore, when used as "haloalkyl" word when combined, said alkyl may be partially or fully substituted with halogen atoms, the halogen atoms may be the same or different. “卤烷基”的实例包括F3C、ClCH2、CF3CH2和CF3CCl2。 Examples of "haloalkyl" include F3C, ClCH2, CF3CH2 and CF3CCl2. 术语“卤链烯基”、“卤炔基”和“卤烷氧基”等的定义与术语“卤烷基”类似。 The term "halo alkenyl", "halo alkynyl group" and "haloalkoxy" and defined with the term "haloalkyl" is similar. “卤链烯基”的实例包括(Cl2)C＝CHCH2和CF3CH2CH＝CHCH2。 Examples of the "halo alkenyl" include (Cl2) C = CHCH2 and CF3CH2CH = CHCH2. “卤炔基”的实例包括HC≡CCHCl、CF3C≡C、CCl3C≡C和FCH2C≡CCH2。 Examples of the "halo alkynyl" include HC≡CCHCl, CF3C≡C, CCl3C≡C and FCH2C≡CCH2. “卤烷氧基”的实例包括CF3O、CCl3CH2O、HCF2CH2CH2O和CF3CH2O。 Examples of "haloalkoxy" include CF3O, CCl3CH2O, HCF2CH2CH2O and CF3CH2O.

在取代基中的碳原子总数以“Ci-Cj”前缀表示，其中i和j是1-8的数字。 The total number of carbon atoms in the substituent in "Ci-Cj" prefix where i and j are numbers 1-8. 例如，C1-C4烷基磺酰基表示甲磺酰基至丁磺酰基；C2烷氧基烷基表示CH3OCH2；C3烷氧基烷基表示，例如，CH3CH(OCH3)、CH3OCH2CH2或CH3CH2OCH2；而C4烷氧烷基表示总共含有4个碳原子的烷氧基取代的烷基的不同异构体，实例包括CH3CH2CH2OCH2和CH3CH2OCH2CH3。 For example, C1-C4 alkylsulfonyl group represents mesyl to butylsulfonyl; C2 alkoxyalkyl denotes CH3OCH2; C3 alkoxyalkyl group represents, for example, CH3CH (OCH3), CH3OCH2CH2 or CH3CH2OCH2; and C4 alkoxy alkyl group represents an alkoxy group containing a total of four carbon atoms substituted alkyl groups of different isomers, examples include CH3CH2CH2OCH2 and CH3CH2OCH2CH3. 在上述陈述中，当式I的化合物含有杂环时，所有的取代基都通过取代任何存在的碳或氮上的氢而通过所述的碳或氮连接于该环上。 In the above statement, when the compound of formula I contains a heterocyclic ring, all substituents are substituted by any of the presence of hydrogen on a carbon or nitrogen through a carbon or nitrogen, wherein the ring is connected to the.

当基团具有可为氢的取代基时，例如R3，则当该取代基为氢时，认为这相当于所述基团是未取代的。 When a group having a hydrogen substituent, for example R3, then when this substituent is hydrogen, that this is equivalent to said group is unsubstituted.

式I的化合物可以作为一种或多种立体异构体存在。 The compounds of formula I can be used as one or more stereoisomers. 各种立体异构体包括对映体、非对映体、阻转异构体和几何异构体。 Various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. 本领域技术人员将理解，当一种立体异构体相对于其它立体异构体为富集时或当与其它立体异构体分离时，其可能更有活性/或可能显示有益效果。 Those skilled in the art will appreciate that when one stereoisomer relative to the other stereoisomer or when enrichment when separated from the other stereoisomers, may be more active / or may show beneficial effects. 另外，本领域技术人员知道如何分离、富集和/或选择性制备所述的立体异构体。 Further, the skilled person knows how to separate, enrich, and / or selectively prepare said stereoisomers of. 因此，本发明的化合物可以作为立体异构体的混合物、单个立体异构体存在，或者作为旋光活性的形式存在。 Accordingly, the compounds of the present invention can be used as a mixture of stereoisomers, individual stereoisomers, or present as an optically active form.

式I的化合物的盐包括与无机或有机酸，如氢溴酸、盐酸、硝酸、磷酸、硫酸、醋酸、丁酸、富马酸、乳酸、马来酸、丙二酸、草酸、丙酸、水杨酸、酒石酸、4-甲苯磺酸或戊酸成的酸加成盐。 Salts of the compounds of formula I include salts with mineral or organic acids, such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic, tartaric, 4-toluenesulfonic or valeric acid as acid addition salts.

出于成本、化学合成或应用的容易和/或生物活性原因，本发明的方法、繁殖体和组合物优选涉及以下优选的化合物：优选1.式I的化合物，其中A和B都为O；R7为苯基环或选自下组的5或6元杂芳环 Because of cost, ease of chemical synthesis or application, and / or biological activity reasons, the method of the invention, propagules and compositions preferably involve the following preferred compounds: Preferred 1. The compounds of formula I, wherein A and B are both O; R7 is selected from the group phenyl ring or a 5- or 6-membered heteroaryl ring 和 And 每个环任选地被1至3个独立地选自R9的取代基取代；Q为O、S、NH或NR9；且W、X、Y和Z独立地为N、CH或CR9，条件是在J-3和J-4中，W、X、Y或Z至少之一是N。 Each ring is optionally substituted with 1 to 3 substituents independently selected from R9 substituents; Q is O, S, NH or NR9; and W, X, Y and Z are independently N, CH or CR9, provided that in J-3 and J-4 in, W, X, Y or Z is at least one N.

优选2.优选1的化合物，其中R1、R2和R8都为H；R3为任选地被卤素、CN、OCH3或S(O)PCH3取代的C1-C4烷基；R4连接于2位；R4为CH3、CF3、OCF3、OCHF2、CN或卤素；R5为H、CH3或卤素；R6为CH3、CF3或卤素；R7为苯基或2-吡啶基，它们各自任选地被取代；并且 Preferably 2. The compounds of Preferred 1 wherein R1, R2 and R8 are both H; R3 is optionally substituted with a halogen, CN, OCH3 or S (O) PCH3 C1-C4 alkyl; R4 is connected to two; R4 is CH3, CF3, OCF3, OCHF2, CN or halogen; R5 is H, CH3 or halogen; R6 is CH3, CF3 or halogen; R7 is phenyl or 2-pyridyl, each optionally substituted; and

P为0、1或2。 P is 0, 1 or 2.

优选3.优选2的化合物，其中R3为C1-C4烷基而R6为CF3。 3. The preferred compound is preferably 2, wherein R3 is C1-C4 alkyl and R6 is CF3.

优选4.优选2的化合物，其中R3为C1-C4烷基而R6为Cl或Br。 4. A preferred compound is preferably 2, wherein R3 is C1-C4 alkyl and R6 is Cl or Br.

如上所指出，R7(尤其)为苯基、苄基、5或6元杂芳环、萘基环体系或芳香性的8、9或10元稠杂双环体系，每个环或环体系任选地被1至3个独立地选自R9的取代基取代。 As noted above, R7 (in particular) is phenyl, benzyl, a 5- or 6-membered heteroaromatic ring, naphthyl ring system or an aromatic 8, 9 or 10-membered fused bicyclic heteroaryl system, each ring or ring system optionally substituted with 1 to 3 substituents independently selected from R9 substituents. 与这些R7基团有关的术语“任选地取代”指未取代或至少具有一个非氢取代基的基团，所述取代基不使未取代的类似物所具有的无脊椎害虫防治活性消失。 Terminology related with these R7 groups "optionally substituted" means unsubstituted or having at least one non-hydrogen substituent group, the substituent not to invertebrate pest control activity possessed by the unsubstituted analog disappears. 还注意下面的J-1至J-4指5或6元杂芳环。 Also note the following J-1 to J-4 refers to the 5 or 6 membered heterocyclic aromatic ring. 被1至3个R9任选地取代的苯基环的实例是在示意图1中所示的J-5，其中r为0至3的整数。 Is optionally substituted with 1 to 3 R9 Examples of substituted phenyl ring is J-5 as shown in Scheme 1, where r is an integer from 0 to 3. 被1至3个R9任选地取代的苯基环的实例是在示意图1中所示的J-6，其中r为0至3的整数。 Is optionally substituted with 1 to 3 R9 Examples of substituted phenyl ring in the J-6 is shown in Scheme 1, where r is an integer from 0 to 3. 被1至3个R9任选地取代的萘基环体系的实例是在示意图1中所示的J-59，其中r为0至3的整数。 Examples 1 to 3 R9 is optionally substituted naphthyl ring system is J-59 as shown in Scheme 1, where r is an integer from 0 to 3. 被1至3个R9任选地取代的5或6元杂芳环的实例包括在示意图1中所示的J-7至J-58，其中r为0至3的整数。 R9 is 1-3 Examples of optionally substituted 5 or 6 membered heteroaromatic ring comprising at J-7 through J-58 as shown in Scheme 1, where r is an integer from 0 to 3. 注意J-7至J-26是J-1的实例，J-27至J-41是J-2的实例，而J-46至J-58是J-3和J-4的实例。 Note that J-7 through J-26 are examples of J-1, J-27 through J-41 are examples of J-2, and J-46 through J-58 are examples of J-3 and J-4's. 需要取代以满足其化合键的氮原子被H或R9取代。 Substituted to meet the needs of their nitrogen atom is substituted with a compound bond H or R9. 注意一些J基可以仅被少于3个R9基团取代(例如J-19、J-20、J-23至J-26和J-37至J-40可以仅被一个R9取代)。 Note that some J groups can only be less than 3 R9 groups substituted (e.g., J-19, J-20, J-23 to J-26 and J-37 through J-40 can only be substituted with one R9). 被1至3个R9任选地取代的芳香性的8、9或10元稠合杂双环体系的实例包括在示意图1中所示的J-60至J-90，其中r为0至3的整数。 Examples 1-3 is R9 optionally substituted aromatic 8,9 or 10-membered fused bicyclic heteroaryl systems include shown in Scheme 1 to J-60 J-90, wherein r is 0 to 3 integer. 虽然R9显示在J-5至J-90结构中，但注意它们并不是必须存在的，因为它们是任选的取代基。 While R9 is displayed in the J-5 to J-90 structure, but note that they are not necessarily present, since they are optional substituents. 注意当(R9)r与J基团之间的连接点表示为不固定时，(R9)r可以连接于J基团的任合存在的碳原子上。 Note that when the attachment point (R9) r and the J group is expressed as the time is not fixed, (R9) r can be attached to a carbon atom of the J group is present in any combination. 注意当J基团上的连接点表示为不固定时，J基团可以通过取代H原子而通过J基团上的任何存在的碳连接于式I的其余部分。 Note that when the attachment point on the J group is represented as not fixed, J group may be substituted by H atoms by the presence of any carbon on the J group is connected to the remainder of Formula I.

示意图1 Illustration 1

或 Or 可以使用下述路线1-22中所描述的一种或多种方法和变体制备式I的化合物。 The method of one or more compounds of formula I and variants prepared from 1-22 by the following routes described may be used. 在下面式2-40的化合物中，A、B和R1至R9如在发明内容中所定义，除非另有说明。 In the compounds of the following formula 2-40, A, B, and to R9 are as defined in the Summary of the Invention R1, unless otherwise indicated. 式Ia-d、2a-d、3a、4a-d、5a-b、17a-c、18a和32a-b的化合物是式I、2、3、4、5、17、18和32的化合物的不同亚类，Het为如下所示的基团：Het是 Formula Ia-d, 2a-d, 3a, 4a-d 5a-b, 17a-c, compound, 18a and 32a-b of the formula I, the compound 2,3,4,5,17,18 and 32 different subclasses, Het is a group as follows: Het is 制备式Ia的化合物的典型方法如路线1所描述。 A typical process for preparing a compound of formula Ia as described in Scheme 1.

路线1 Route 1 Ia(A为O)Ib(A为S)路线1的方法包括在酸清除剂存在下偶联式2的胺与式3的酰氯，产生式Ia的化合物。 Ia (A to O) Ib (A is S) The method of Scheme 1 include the presence of an acid scavenger in the compound of formula 2 under coupling an amine of formula 3 acid chloride, to produce Formula Ia. 典型的酸清除剂包括胺碱，如三乙胺、N，N-二异丙基乙胺和吡啶；其它清除剂包括氢氧化物，如氢氧化钠和氢氧化钾，以及碳酸盐，如碳酸钠和碳酸钾。 Typical acid scavengers include amine bases such as triethylamine, N, N- diisopropylethylamine and pyridine; other scavengers include hydroxides such as sodium hydroxide and potassium hydroxide, and carbonates, e.g. sodium carbonate and potassium carbonate. 在某些情况下，采用聚合物载酸清除剂，如聚合物结合的N，N-二异丙基乙胺和聚合物结合的4-(二甲基氨基)吡啶。 In some cases, the use of an acid scavenger polymer carrier, such as polymer-bound N, N- diisopropylethylamine and polymer-bound 4- (dimethylamino) pyridine. 偶联可以在适合的惰性溶剂，如四氢呋喃、二噁烷、乙醚或二氯甲烷中进行，获得式Ia的酰基苯胺。 Coupling may be, such as tetrahydrofuran, dioxane, diethyl ether or methylene chloride in a suitable inert solvent, to obtain the anilide of Formula Ia.

通过用多种标准硫转移试剂之一处理，可以在随后的步骤中从相应的式Ia的酰胺获得式Ib的硫代酰胺，所述硫转移试剂包括五硫化二磷和Lawesson试剂(2，4-二(4-甲氧基苯基)-1，3-二硫-2，4-diphosphetane-2，4-二硫化物)如路线2所示，制备式Ia的化合物的另一方法包括在脱水剂存在下偶联式2的胺与式4的酸，所述脱水剂如二环己基碳二亚胺(DCC)、1，1'-羰基-二咪唑、二(2-氧-3-噁唑烷基)次磷酰氯或苯丙三唑-1-基氧-三(二甲基氨基)磷鎓六氟磷酸盐。 By using one of several standard sulfur transfer reagent, of Formula Ib can be obtained from the corresponding thioamide amide of formula Ia in a subsequent step, the sulfur transfer reagents include phosphorus pentasulfide and Lawesson's reagent (2,4-bis ( 4-methoxyphenyl) -1,3-disulfide -2,4-diphosphetane-2,4- disulfide) The course, another method of preparing compounds of formula Ia shown include the presence of a dehydrating agent By coupling an amine of formula 2 with an acid of formula 4, the dehydrating agent such as dicyclohexyl carbodiimide (DCC), 1,1'- carbonyl - diimidazole, bis (2-oxo-3-oxazolidine yl) phosphinic chloride or benzotriazole-1-yloxy - tris (dimethylamino) phosphonium hexafluorophosphate.

路线2 Route 2 聚合物载剂在这里也有用，如聚合物结合的环己基碳二亚胺。 Polymeric carrier is also useful here, such as polymer-bound cyclohexyl carbodiimide. 偶联可在适合的惰性溶剂，如二氯甲烷或N，N-二甲基甲酰胺中进行。 Coupling can be in a suitable inert solvent, such as dichloromethane or N, N- dimethyl formamide. 路线1和2的合成方法是用于制备式I的化合物的多种偶联方法的代表性实例；这类偶联反应的合成文献很多。 Synthesis Route 1 and 2 are representative examples of a variety of coupling methods for preparing a compound of formula I; the synthetic literature many such coupling reaction.

本领域技术人员还将认识到，可以通过多种熟知的方法由式4的酸制备式3的酰氯。 Those skilled in the art will also recognize that, through a variety of well-known methods by the formula 4 acid chloride of formula 3. 例如，可以通过在催化量的N，N-二甲基甲酰胺存在下，在如甲苯或二氯甲烷的惰性溶剂中，使式4的羧酸与亚硫酰氯或乙二酰氯反应而容易地由式4的羧酸制得式3的酰氯。 For example, by a catalytic amount of N, N- dimethylformamide under the presence, in an inert solvent such as toluene or methylene chloride, and the carboxylic acid with thionyl chloride or oxalyl chloride with the reaction formula 4 readily from a carboxylic acid of formula 4 to obtain acid chloride of formula 3.

如路线3所示，式2a的胺通常通过硝基的催化加氢而由相应的式5的2-硝基苯甲酰胺得到。 As shown in Scheme 3, amines of formula 2a is usually obtained from the corresponding 2- nitrobenzamide formula 5 by catalytic hydrogenation of the nitro group.

路线3 Route 3 5 2a 2b(R1不是H)典型的方法包括在金属催化剂如钯/碳或氧化钯存在下，在羟基溶剂如乙醇和异丙醇中用氢还原。 5 2a 2b (R1 not H) A typical process comprises a metal catalyst such as palladium / carbon or palladium oxide, in a hydroxylic solvent such as ethanol and isopropanol with hydrogen reduction. 式2a的胺也可以通过在醋酸中用锌还原而制得。 Type 2a amines can also be prepared by reduction with zinc acetate. 这些方法已发表于化学文献中。 These methods have been published in the chemical literature. R1取代基，如C1-C6烷基可以在此阶段通过熟知的方法，包括直接烷基化或通过胺的还原烷基化的一般优选的方法而引入。 R1 substituents such as C1-C6 alkyl group can at this stage by known methods, including the generally preferred method of direct alkylation or by reductive alkylation of the amine introduced. 如路线3中进一步所示，通常采用的方法是在还原剂如氰基硼氢化钠存在下混合苯胺2a与乙醛，产生式2b的化合物，其中R1为C1-C6烷基。 As further shown in line 3, the method generally used is a compound in the reducing agent mixed aniline 2a with acetaldehyde to produce the Formula 2b as the presence of sodium cyanoborohydride, wherein R1 is a C1-C6 alkyl.

路线4显示在碱如氢化钠或正丁基锂存在下，在惰性溶剂如四氢呋喃或N，N-二甲基甲酰胺中，可以用适合的烷基化剂或酰化剂，如烷基卤或氯甲酸烷基酯或酰氯将化合物Ic烷基化或酰化，得到式Id的酰基苯胺，其中R1不是H。 Route 4 shows a base such as sodium hydride or n-butyllithium, in an inert solvent such as tetrahydrofuran or N, N- dimethyl formamide, may be suitable alkylating agent or acylating agent, such as an alkyl halide or alkyl chloroformate or acid chloride compound Ic alkylated or acylated, acyl aniline of formula Id wherein R1 is other than H.

路线4 Route 4 Ic Id(R1不是H)式5a的中间体酰胺容易地从可商购的2-硝基苯甲酸制备。 Ic Id (R1 not H) the intermediate amide of formula 5a is readily prepared from commercially available benzoic acid 2-nitro. 可以使用形成酰胺的典型方法。 Amide can be formed using typical methods. 如路线5中所示，这些方法包括使用例如DCC直接脱水偶联式6的酸与式7的胺，并将酸转化成活化形式如酰氯或酸酐，接着与胺偶联，形成式5a的酰胺。 As shown in Scheme 5, these methods include direct dehydration using for example DCC coupling an acid of formula 6 with an amine of formula 7, and the acid is converted to an activated form such as the acid chloride or anhydride, followed by coupling with an amine to form amides of Formula 5a .

路线5 Route 5 5a(B为O)5b(B为S)氯甲酸烷基酯，如氯甲酸乙酯或氯甲酸异丙酯，对于涉及酸活化的这类反应是特别有用的试剂。 5a (B is O) 5b (B is S) alkyl chloroformate, such as ethyl chloroformate or isopropyl chloroformate, for the type of reaction involving activation of the acid are particularly useful reagents. 关于酰胺形成的方法的化学文献很多。 Many methods for amide formation on the chemical literature. 通过使用可商购的硫转移试剂，如五氯化二磷和Lawesson试剂而容易地将式5a的酰胺转化成式5b的硫代酰胺。 By using commercially available sulfur transfer reagent, such as phosphorus pentachloride and Lawesson's reagent and easily converted to an amide of formula of formula 5a and 5b thioamide.

式2c或2d的中间体邻氨基苯甲酰胺也可以分别由式8或9的靛红酸酐制备，如路线6所示。 Intermediates of formula 2c or 2d anthranilamide be, as shown in Scheme 6 are prepared from the isatoic anhydride of Formula 8 or 9.

路线6 Route 6 2d(R1不是H)典型的方法包括在极性非质子溶剂如吡啶和N，N-二甲基甲酰胺中，在室温至100℃的温度下混合等摩尔量的胺7与靛红酸酐。 2d (R1 not H) Typical methods include in a polar aprotic solvent such as a molar amount of pyridine and N, N- dimethyl formamide, at a temperature of room temperature to 100 ℃ mixing the amine 7 with the isatoic anhydride. R1取代基如烷基和取代的烷基可以通过靛红酸酐8的碱催化的烷基化来引入，所述烷基化用已知的烷基化试剂R1-Lg(其中Lg为可亲核取代的离去基团，如卤素、烷基或芳基磺酸酯或烷基硫酸酯)进行，产生烷基取代的中间体9。 R1 substituents such as alkyl and substituted alkyl may be introduced by isatoic anhydride 8 base-catalyzed alkylation, the alkylated by known alkylating agent R1-Lg (wherein Lg is a nucleophilically substituted leaving group such as halogen, alkyl or aryl sulfonates or alkyl sulfates) was found to produce the alkyl substituted intermediate 9. 式8的靛红酸酐可以通过在Coppola，Synthesis 1980，505-36中所描述的方法来制备。 Isatoic anhydride of formula 8 may be in the process of Coppola, Synthesis 1980,505-36 be prepared as described by.

如在路线7中所示，用于制备特定的式Ic的化合物的的另一方法包括胺7与式10的苯丙噁嗪酮的反应。 Another method as shown in line 7 in the preparation of compounds of formula Ic of particular used include amines 7 and 10 of formula phenylpropyl oxazinone reaction.

路线7 Route 7

路线7的反应可以无溶剂地或在多种适合的溶剂，包括四氢呋喃、乙醚、吡啶、二氯甲烷或氯仿中，于室温至溶剂回流的最佳温度下进行。 7 may route reaction without solvent or in a variety of suitable solvents including tetrahydrofuran, diethyl ether, pyridine, dichloromethane or chloroform, at room temperature to the reflux temperature of the solvent will be the optimum. 苯丙噁嗪酮与胺的一般反应产生邻氨基苯甲酰胺，这在化学文献中有很多记载。 Benzenepropanoic oxazinone reaction with an amine of general anthranilamide, which are well documented in the chemical literature. 关于苯丙噁嗪酮化学的综述，参见Jakobsen等人，Biorganicand Medicinal Chemistry，2000，8，2095-2103以及其中引用的文献。 Overview on phenylpropanoid oxazinone chemistry see Jakobsen et al., Biorganicand Medicinal Chemistry, 2000,8,2095-2103 and references cited therein. 还参见Coppola，J，Heterocyclic Chemistry 1999，36，563-588。 See also Coppola, J, Heterocyclic Chemistry 1999,36,563-588.

可以通过多种方法制备式10的苯丙噁嗪酮。 There are several ways formula phenylpropanoid 10 oxazinone. 在路线8-9中详述的两种方法是特别有用的。 Two methods detailed in Scheme 8-9 are particularly useful. 在路线8中，通过偶联式4a的吡唑羧酸与式11的邻氨基苯甲酸而直接制备式10的苯丙噁嗪酮。 In line 8, by coupling type 4a pyrazole anthranilic acid of formula 11, styrene-acrylic acid and direct formula 10 oxazinone.

路线8 Route 8 这包括在叔胺如三乙胺或吡啶存在下，将甲磺酰氯顺序加入式4a的吡唑羧酸中，随后加入式11的邻氨基苯甲酸，然后第二次加入叔胺和甲磺酰氯。 This includes a tertiary amine such as triethylamine or pyridine, sequential addition of methanesulfonyl chloride of formula 4a pyrazole carboxylic acid, anthranilic acid of Formula 11 was then added, and then a second addition of tertiary amine and methanesulfonyl chloride . 该方法通常提供良好的苯丙噁嗪酮收率，并且在实施例6和8中进行更详细的说明。 The method generally provides good phenylpropyl oxazinone yield, and in more detail in Example 6 and 8.

路线9描述了制备式10的苯丙噁嗪酮的另一方法，包括偶联式3a的吡唑酰氯与式8的靛红酸酐，直接得到式10的苯丙噁嗪酮。 Scheme 9 depicts another method of preparing formula benzenepropanoic 10 oxazinone, comprising coupling the pyrazole acid chloride of formula 3a with the isatoic anhydride of formula 8, formula 10 is obtained directly phenylpropyl oxazinone.

路线9 Route 9 溶剂如吡啶或吡啶/乙腈适合于该反应。 Solvent such as pyridine or pyridine / acetonitrile is suitable for the reaction. 式3a的酰氯可以通过各种合成方法如用亚硫酰氯或乙二酰氯氯化而由相应的式4a的酸得到。 The acid chloride of formula 3a can be obtained e.g. from the corresponding acids of Formula 4a with thionyl chloride or oxalyl chloride by a variety of synthetic methods.

式8的靛红酸酐可以由式13的靛红制得，如在路线10中所述。 Isatoic anhydride of formula 8 may be prepared from isatin of Formula 13 prepared as described in Scheme 10.

路线10 Route 10 使用文献中记载的方法由式12的苯胺衍生物获得式13的靛红。 Using the method described in the literature by the aniline derivative of formula 12 to obtain the isatin of Formula 13. 用过氧化氢氧化靛红13通常提供相应的靛红酸酐8的良好收率(Angew.Chem.Int.Ed.Engl.1980，19，222-223)。 Oxidation with hydrogen peroxide Isatoic 13 generally provides appropriate isatoic anhydride in good yield (Angew.Chem.Int.Ed.Engl.1980,19,222-223) 8 in. 靛红酸酐也可以通过许多已知的方法由邻氨基苯甲酸11得到，所述方法包括11与光气或光气等价物反应。 Isatoic anhydride can also be obtained by a number of methods known anthranilic acid 11, 11 or equivalent, the method comprising reacting with phosgene phosgene.

式4的代表性酸的合成在路线11-16中描述。 Synthesis of representative acids of Formula 4 is described in Scheme 11-16. 式4a的吡唑的合成在路线11中显示。 Synthesis of pyrazoles of Formula 4a in Scheme 11 is displayed.

路线11 Route 11 在路线11中的式4a的化合物的合成包括作为关键步骤的，通过用式15的化合物(其中Lg是如上定义的离去基团)烷基化或芳基化式14的吡唑而引入R7取代基。 Synthesis of compound of Formula 11 in Scheme 4a includes as a key step, the compound of formula 15 (wherein Lg is a leaving group as defined above) alkylated or arylated pyrazole of formula 14 is introduced R7 substituents. 甲基的氧化产生吡唑羧酸。 The oxidation of methyl pyrazole carboxylic acid. 一些更优选的R6基包括卤烷基。 Some of the more preferred R6 groups include haloalkyl.

式4a的吡唑的合成也显示在路线12中。 Pyrazole of formula 4a is also shown in Scheme 12.

路线12 Route 12 这些酸可以通过将式18的化合物金属化和作为关键步骤羧化而制备。 These acids can be produced by a compound of formula 18 and the metalization as a key step carboxylation prepared. R7基以类似于路线11的方式引入，即通过用式15的化合物烷基化或芳基化。 R7 group in manner similar to the route 11 of the introduction, i.e. a compound of formula 15 by alkylation or arylation. 代表性的R6基包括例如氰基、卤烷基和卤素。 Representative R6 groups include e.g. cyano, haloalkyl and halogen.

该方法对于如路线13所示制备式4b的1-(2-吡啶基)吡唑羧酸尤其有用。 The method for such routes of 1- (2-pyridyl) 13 prepared pyrazole carboxylic acid of formula 4b is particularly useful.

路线13 Route 13 式17的吡唑与式15a的2，3-二卤代吡啶的反应获得式18a的1-吡啶基吡唑的良好收率，其对所需区域化学具有良好的特异性。 The reaction pyrazole of Formula 15a and Formula 17, 2,3-dihalo-pyridine of formula 18a 1- pyridyl pyrazole good yield, which has the desired regiochemistry good specificity. 用二异丙基酰胺锂(LDA)将18a金属化，然后用二氧化碳使锂盐骤冷，得到式4b的1-(2-吡啶基)吡唑羧酸。 With lithium diisopropylamide (LDA) to 18a metallization, the lithium salt with carbon dioxide and then quenched to give a formula 4b of 1- (2-pyridyl) pyrazole carboxylic acid. 这些方法的另外的细节在实施例1、3、6、8和10中给出。 Further details of these processes are given in Examples 1,3,6,8 and 10.

式4c的吡唑的合成在路线14中描述。 Pyrazole Formula 4c is described in Scheme 14.

路线14 Route 14 路线14涉及式19的任选地取代的苯肼与式20的酮基丙酮酸盐反应，生成式21的吡唑酯。 Scheme 14 relates to formula 19 is optionally substituted phenylhydrazine of the formula 20-keto-pyruvate reaction, pyrazole ester of formula (21). 酯水解产生式4c的吡唑酸。 Ester hydrolysis type 4c pyrazole acid. 该方法对于制备R7为任选地取代的苯基而R6为卤烷基的化合物特别有用。 The method for the preparation of R7 is optionally substituted phenyl and R6 is haloalkyl of particularly useful compounds.

式4c的吡唑酸的另一合成在路线15中描述。 Another synthesis of pyrazole acids of Formula 4c is described in Scheme 15.

路线15 Route 15 路线15的方法涉及适当地取代的亚胺基卤化物22与式23的取代的丙炔酸酯或式25的丙烯酸酯的3+2环加成。 3 + 2 ring line 15 is directed to a method appropriately substituted imino halide substituted propiolates of Formula 23 or 22 with the acrylic acid ester adduct of formula 25. 用丙烯酸酯的环加成需要附加的将中间体吡唑啉氧化成吡唑。 Cycloaddition with acrylates requires additional oxidation of the intermediate pyrazoline to pyrazole. 酯水解产生式4c的吡唑酸。 Ester hydrolysis type 4c pyrazole acid. 该反应优选的亚胺基卤包括式26的三氟甲基亚胺基氯和式27的亚胺基二溴。 The reaction is preferably the imino halide of formula 26 include trifluoromethyl imino chloride and the imine of formula 27 dibromo. 诸如26的化合物是已知的(J.Heterocycl.Chem.1985，22(2)，565-8)。 Compounds such as 26 are known (J.Heterocycl.Chem.1985,22 (2), 565-8). 诸如27的化合物可由已知方法获得(Tetrahedron Letters 1999，40，2605)。 Compounds such as 27 may be obtained by known methods (Tetrahedron Letters 1999,40,2605). 这些方法对于制备其中R7为任选地取代的苯基而R6为卤烷基或溴的化合物特别有用。 These methods for preparing a compound wherein R7 is optionally substituted phenyl and R6 is particularly useful compound haloalkyl or bromo.

式17的起始吡唑是已知化合物或者可以根据已知方法制备。 Starting pyrazole of formula 17 are known compounds or may be prepared according to known methods. 式17a的吡唑(式17的化合物，其中R6为CF3而R8为H)可以通过文献方法制备(J.Fluorine Chem.1991，53(1)，61-70)。 Formula 17a pyrazole (compound of formula 17, wherein R6 is CF3 and R8 is H) can be prepared by literature methods (J.Fluorine Chem.1991,53 (1), 61-70). 式17c的吡唑(式17的化合物，其中R6为Cl或Br而R8为H)也可以通过文献方法制备(Chem.Ber.1966，99(10)，3350-7)。 Formula 17c pyrazole (compound of formula 17, wherein R6 is Cl or Br and R8 is H) can also be prepared by literature methods (Chem.Ber.1966,99 (10), 3350-7). 在路线16中描述了制备化合物17c的另一有用方法。 Another useful method is described for preparing compound 17c in line 16.

路线16 Route 16 在路线16的方法中，用正丁基锂将式28的氨磺酰吡唑金属化，随后用六氯乙烷(R6为Cl)或1，2-二溴四氯乙烷(R6为Br)直接卤化阴离子，产生式29的卤化衍生物。 In the method of the route 16, with n-butyllithium to a sulfonyl amino pyrazole of formula 28 metallization, followed by hexachloroethane (R6 is Cl) or 1,2-dibromo-tetrachloroethane (R6 is Br ) direct halide anion production halogenated derivatives 29. 在室温下用三氟醋酸(TFA)除去氨磺酰基进行得很完全，并以良好收率产生式17c的吡唑。 At room temperature with trifluoroacetic acid (TFA) to remove sulfamoyl went completely, and in good yield to produce a pyrazole of formula 17c. 本领域技术人员将认识到，式17c是式17b的互变异构体。 Skilled in the art will recognize that Formula 17c is a tautomer of Formula 17b thereof. 这些方法的进一步实验细节在实施例8和10中描述。 Further experimental details of these methods in Example 8 and 10 are described.

式4d的吡唑羧酸，其中R6为H、C1-C6烷基或C1-C6卤烷基，可以通过概述于路线17中的方法制备。 Pyrazole carboxylic acid of formula (4d), wherein R6 is H, C1-C6 alkyl or C1-C6 haloalkyl group, may be prepared by a method in line 17 are summarized in.

路线17 Route 17 在适合的有机溶剂中使式30的化合物，其中R13为C1-C4烷基，与适合的碱反应，在用酸如乙酸中和后产生式31的环化产物。 In an organic solvent a compound of formula 30 is suitable, wherein R13 is C1-C4 alkyl, is reacted with a suitable base, after neutralization with an acid such as acetic acid to produce the cyclized product of Formula 31. 适合的碱可以为，例如但不限于，氢化钠、叔丁醇钾、dimsyl钠(CH3S(O)CH2-Na+)、碱金属(例如锂、钠或钾)碳酸盐或氢氧化物、四烷基(例如甲基、乙基或丁基)铵氟化物或氢氧化物或2-叔丁基亚氨基-2-二乙氨基-1，3-二甲基-全氢-1，3，2-二氮杂膦(diazaphosphonine)。 Suitable base may be, for example but not limited to, sodium hydride, potassium t-butoxide, dimsyl sodium (CH3S (O) CH2-Na +), alkali metals (e.g. lithium, sodium or potassium) carbonates or hydroxides, four alkyl (e.g. methyl, ethyl or butyl) ammonium fluorides or hydroxides, or 2-tert-butyl-amino-2-diethylamino-1,3-dimethyl - perhydro-1,3, 2-aza-phosphine (diazaphosphonine). 适合的有机溶剂可以为，例如但不限于，丙酮、乙腈、四氢呋喃、二氯甲烷、二甲亚砜或N，N-二甲基甲酰胺。 Suitable organic solvents may be, for example but not limited to, acetone, acetonitrile, tetrahydrofuran, dichloromethane, dimethylsulfoxide or N, N- dimethylformamide. 环化反应通常在约0至120℃的温度范围内进行。 The cyclization reaction is usually carried out in a temperature range of about 0 to 120 ℃. 溶剂、碱、温度和加成时间的作用都是相互依赖的，并且选择反应条件对于减少副产物形成是重要的。 Solvent, base, temperature and addition time are all interdependent action, and the reaction conditions are selected to reduce by-product formation is important. 优选的碱是氟化四丁基铵。 The preferred base is tetrabutylammonium fluoride.

式31的化合物的脱水给出式32的化合物，随后将羧酸酯官能团转化为羧酸，得到式4d的化合物。 Dehydrating a compound of formula 32 to give a compound of formula 31, followed by conversion of the carboxylic ester function to carboxylic acid, to obtain a compound of formula (4d). 脱水通过用催化量的适合的酸处理而实现。 Dehydrated with an appropriate acid treatment is achieved by catalytic amount. 这里催化酸可以为，例如但不限于，硫酸。 Here catalytic acid can be, for example but not limited to, sulfuric acid. 通常使用有机溶剂进行该反应。 Typically the reaction is carried out using an organic solvent. 本领域技术人员将认识到，脱水反应可以在约0至200℃，更优选约0至100℃的温度范围内，在多种溶剂中进行。 Those skilled in the art will recognize, the dehydration reaction can be from about 0 to 200 ℃, more preferably within a temperature range of about 0 to 100 ℃, and in a variety of solvent. 对于路线17的方法中的脱水，含有醋酸的溶剂和约65℃的温度是优选的。 Method for route 17 in the dehydration, the temperature of the solvent containing acetic acid and about 65 ℃ are preferred. 可以通过多种方法将羧酸酯化合物转化为羧酸化合物，所述方法包括在无水条件下的亲核裂解或涉及使用酸或碱的水解方法(参见TWGreene和PGMWuts，Protective Groups in Organic Synthesis，2nd ed.，John Wiley & Sons，Inc.，New York，1991，pp.224-269的方法综述)。 There are several ways the carboxylic acid ester compound into a compound, the method comprising under anhydrous conditions involving nucleophilic cleavage or hydrolysis using an acid or an alkali method (see TWGreene and PGMWuts, Protective Groups in Organic Synthesis, 2nd ed, John Wiley & amp;. Sons, Inc., New York, 1991, Methods of pp.224-269 in). 对于路线17的方法，碱催化的水解方法是优选的。 Method for route 17, base-catalyzed hydrolysis method is preferable. 适合的碱包括碱金属(例如锂、钠或钾)氢氧化物。 Suitable bases include alkali metal (e.g., lithium, sodium or potassium) hydroxides. 例如，可以将酯溶解在水和醇如乙醇的混合物中。 For example, the ester can be dissolved in a mixture of water and an alcohol such as ethanol. 在用氢氧化钠或氢氧化钾处理时，酯皂化，提供羧酸的钠盐或钾盐。 When treated with sodium hydroxide or potassium hydroxide, the ester is saponified to provide the sodium or potassium salts of carboxylic acids. 用强酸如盐酸或硫酸酸化，产生式4d的羧酸。 With a strong acid such as hydrochloric or sulfuric acid, to produce carboxylic acid of formula (4d). 可以通过本领域技术人员已知的方法，包括结晶、萃取和蒸馏来分离羧酸。 Can be made by methods known to the skilled person, including crystallization, extraction and distillation to separate the carboxylic acid.

式30的化合物可以通过概述于路线18中的方法制备。 Compounds of formula 30 may be prepared by Route 18 Method outlined in.

路线18 Route 18 其中R6为H、C1-C4烷基或C1-C6卤烷基，而R13为C1-C4烷基。 Wherein R6 is H, C1-C4 alkyl or C1-C6 haloalkyl, and R13 is C1-C4 alkyl. 在诸如水、甲醇或乙酸的溶剂中用式34的酮处理式33的肼化合物，得到式35的腙。 Hydrazine compounds such as water, methanol or acetic acid solvent with a ketone of formula 34 by treatment of 33, to give the hydrazone of formula 35. 本领域技术人员将认识到，该反应可能需要用任选的酸催化，并且也可能需要升高的温度，这取决于式35的腙的分子取代模式。 Those skilled in the art will recognize, the reaction may require catalysis by an optional acid and may also require elevated temperatures depending on the molecular formula of hydrazone 35 substitution pattern. 在适合的有机溶剂，例如但不限于，二氯甲烷或四氢呋喃中，在酸清除剂如三乙胺存在下，式35的腙与式36的化合物反应，生成式30的化合物。 In a suitable organic solvent, such as, but not limited to, dichloromethane or tetrahydrofuran in the presence of an acid scavenger such as triethyl amine compound, a hydrazone of formula 35 is reacted with a compound of formula 36, ​​formula 30. 该反应通常在约0至100℃的温度下进行。 The reaction is usually carried out at a temperature of about 0 to 100 ℃. 路线18的方法的进一步实验细节在实施例17中说明。 Example 17 Further experimental details are described in the method of Route 18 in the embodiment. 式33的肼化合物可以通过标准方法制备，如通过使相应的式15a的卤代化合物与肼接触。 Hydrazine compound of formula 33 can be prepared by standard methods, such as by reacting the corresponding halo compound of formula 15a is contacted with hydrazine.

式4d的吡唑羧酸，其中R6为卤素，可以通过概述于路线19中的方法制备。 The pyrazole carboxylic acid of formula 4d wherein R6 is halogen, can be prepared in line 19 by a method outlined in.

路线19 Route 19 其中R13为C1-C4烷基。 Wherein R13 is C1-C4 alkyl.

式37化合物的氧化作用任选地在酸存在的条件下进行，生成式32的化合物，随后将羧酸酯官能团转化为羧酸，生成式4d的化合物。 Oxidation of the compound of Formula 37 optionally in the presence of an acid performed, a compound of formula 32, followed by conversion of the carboxylic ester function to the carboxylic acid, the compound of Formula 4d. 氧化剂可以为过氧化氢、有机过氧化物、过硫酸钾、过硫酸钠、过硫酸铵、过硫酸氢钾(例如Oxone)或高锰酸钾。 The oxidizing agent may be hydrogen peroxide, organic peroxides, potassium persulfate, sodium persulfate, ammonium persulfate, potassium hydrogen sulfate (e.g. Oxone) or potassium permanganate. 为了获得完全的转化，至少应当使用相对于式37的化合物而言为1当量的氧化剂，优选约1至2当量。 To obtain complete conversion, at least in terms should be used with respect to the compound of formula 37 is one equivalent of an oxidizing agent, preferably about 1 to 2 equivalents. 该氧化通常在溶剂存在下进行。 The oxidation is typically carried out in the presence of a solvent. 溶剂可以为醚，如四氢呋喃、对二噁烷等，有机酯，如乙酸乙酯、碳酸二甲酯等，或极性非质子有机溶剂如N，N-二甲基甲酰胺、乙腈等。 The solvent may be an ether, such as tetrahydrofuran, p-dioxane, etc., organic esters, such as ethyl acetate, dimethyl carbonate, etc., or a polar aprotic organic solvent such as N, N- dimethylformamide, acetonitrile and the like. 适用于氧化步骤的酸包括无机酸，如硫酸、磷酸等，以及有机酸，如乙酸、苯甲酸等。 Suitable for the oxidation step include inorganic acids, such as sulfuric acid, phosphoric acid, etc., and organic acids, such as acetic acid, benzoic acid and the like. 当使用时，所用的酸相对于式37的化合物而言应大于0.1当量。 When used, the acid phase used for the purposes of a compound of formula 37 should be greater than 0.1 equivalents. 为了获得完全的转化，可以使用1至5当量的酸。 To obtain complete conversion, may be used 1-5 equivalent of acid. 优选的氧化剂是过硫酸钾，并且氧化优选在硫酸存在下进行。 The preferred oxidizing agent is potassium persulfate and the oxidation is preferably carried out in the presence of sulfuric acid. 反应可以通过在所需的溶剂和如果使用的话，在酸中混合式37的化合物而进行。 The reaction solvent may be required and, if used, are mixed in an acid compound of formula 37 is carried out in. 然后可以便利的速度加入氧化剂。 Can then be added at a rate convenient oxidant. 为了获得合理的反应时间以完成反应，反应温度通常在低至约0℃到高至溶剂的沸点内变化，反应时间优选低于8小时。 In order to obtain a reasonable reaction time to complete the reaction, the reaction temperature is usually as low as about 0 ℃ to as high as the boiling point of the solvent changes, the reaction time is preferably less than 8 hours. 所需的产物，式32的化合物，可以通过本领域技术人员已知的方法分离，所述方法包括结晶、萃取和蒸馏。 The desired product, a compound of formula 32, can be accomplished by methods known to those skilled separation, said method comprising crystallization, extraction and distillation. 适于将式32的酯转化成式4d的羧酸的方法已在路线17中得到描述。 Adapted to the ester of formula 32 is converted to a carboxylic acid of Formula 4d methods have been described in Scheme 17. 路线19的方法的进一步实验细节在实施例12和13中说明。 Further experimental details of the route 19 of the method of Examples 12 and 13 illustrated in.

式37的化合物可以由相应的式38的化合物制备，如路线20中所示。 Compounds of formula 37 may be prepared from the corresponding compound of formula 38, such as line 20 in FIG.

路线20 Route 20 其中R13为C1-C4烷基，而R6为卤素。 Wherein R13 is C1-C4 alkyl, and R6 is halo.

用卤化试剂处理式38的化合物，通常在溶剂存在下进行，产生相应的式37的卤代化合物。 With a compound of formula 38 of halogenating reagent, usually in the presence of a solvent, to produce the corresponding halogenated compound of formula 37. 可以使用的卤化剂包括卤氧化磷、三卤化磷、五卤化磷、亚硫酰氯、二卤三烷基正膦、二卤二苯基正膦、草酰氯和光气。 Halogenating agent can be used include phosphorus oxyhalides, phosphorus trihalides, phosphorus pentahalide, thionyl chloride, n-dihalo trialkyl phosphine, diphenyl-n-phosphine dihalide, oxalyl chloride and phosgene. 优选为卤氧化磷和五卤化磷。 Preferably phosphorus oxyhalide and phosphorus pentahalide. 为了获得完全转化，相对于式38的化合物而言，至少应使用0.33当量的卤氧化磷(即卤氧化磷与式18的摩尔比至少为0.33)，优选约0.33至1.2当量。 To obtain complete conversion, relative to the compound of formula 38, using at least 0.33 equivalents of phosphorus oxyhalide (i.e., phosphorus oxyhalide and the formula is at least 18 molar ratio of 0.33), preferably from about 0.33 to 1.2 equivalents. 为了获得完全转化，相对于式38的化合物而言，至少应使用0.20当量的五卤化磷，优选约0.20至1.0当量。 To obtain complete conversion, relative to the compound of formula 38, using at least 0.20 equivalents of phosphorus pentahalide, preferably from about 0.20 to 1.0 equivalents. 该反应中R13为C1-C4烷基的式38的化合物是优选的。 A compound of formula 38 used in this reaction R13 is C1-C4 alkyl are preferred. 用于该卤化的典型溶剂包括卤代烷烃，如二氯甲烷、氯仿、氯丁烷等，芳族溶剂，如苯、二甲苯、氯苯等，醚，如四氢呋喃、对二噁烷、乙醚等，以及极性非质子溶剂如乙腈、N，N-二甲基甲酰胺等。 Typical solvents for this halogenation include halogenated alkanes, such as dichloromethane, chloroform, chlorobutane and the like, aromatic solvents, such as benzene, xylene, chlorobenzene, etc., ethers such as tetrahydrofuran, p-dioxane, ether and the like, and a polar aprotic solvent such as acetonitrile, N, N- dimethylformamide and the like. 任选地，可以加入有机碱，如三乙胺、吡啶、N，N-二甲基苯胺等。 Optionally, an organic base may be added, such as triethylamine, pyridine, N, N- dimethylaniline and the like. 加入催化剂，如N，N-二甲基甲酰胺，也是一种选择。 Addition of a catalyst, such as N, N- dimethylformamide, is also an option. 优选该方法中的溶剂是乙腈并且碱不存在。 Preferably in this method the solvent is acetonitrile and a base is absent. 通常，当使用乙腈溶剂时，既不需要碱也不需要催化剂。 Typically, when using an acetonitrile solvent, neither a base nor a catalyst is required. 优选的方法通过在乙腈中混合式38的化合物而进行。 The preferred method of mixing the compound of formula 38 in acetonitrile is carried out by. 然后在方便的时间内加入卤化试剂，并在所需的温度下放置混合物，直到反应完全。 Was then added over a convenient time halogenating agent, and the mixture was placed at the desired temperature until the reaction was complete. 反应温度通常在20℃至乙腈的沸点之间，并且反应时间通常低于2小时。 The reaction temperature is generally between 20 ℃ to the boiling point of acetonitrile, and the reaction time is usually less than 2 hours. 然后用无机碱，如碳酸氢钠、氢氧化钠等，或有机碱，如乙酸钠中和反应物料。 Then with an inorganic base, such as sodium bicarbonate, sodium hydroxide, etc., or an organic base, such as sodium acetate and the reaction mass. 所需的产物，式37的化合物，可以通过本领域技术人员已知的方法，包括结晶、萃取和蒸馏而得到分离。 The desired product, a compound of formula 37 can be produced by those skilled in the known methods, including crystallization, extraction and distillation separation is obtained.

或者，R6为卤素的式37的化合物可以通过用适合的卤化氢处理相应的式37的化合物而制备，所述的相应的式37的化合物中R6为不同的卤素(例如Cl，用于构成R3为Br的式37)或磺酸酯基，如对甲苯磺酸酯、苯磺酸酯和甲磺酸酯。 Alternatively, R6 halo of the compound of formula 37 with a suitable compound is by treating the corresponding hydrogen halide of formula 37 is prepared, the corresponding compound of formula 37, wherein R6 is a different halogen (e.g. Cl, R3 for constituting of formula 37 is Br) or a sulfonate group such as p-toluenesulfonate, benzenesulfonate and methanesulfonate. 通过该方法，式37起始化合物上的R6卤素或磺酸酯取代基分别被，例如来自溴化氢或氯化氢的Br或Cl取代。 By this method, R6 halogen or sulfonate compound of formula 37 starting on the substituents are respectively, e.g., Br or Cl from hydrogen bromide or hydrogen chloride substitution. 反应在适合的溶剂，如二溴甲烷、二氯甲烷或乙腈中进行。 Reaction in a suitable solvent, such as dibromomethane, dichloromethane or acetonitrile. 反应可在大气压或接近大气压下进行，或者可以在压力容器中在高于大气压下进行。 The reaction can be carried out under atmospheric pressure or near atmospheric pressure, or may be carried out at higher than atmospheric pressure in a pressure vessel. 当式37的起始化合物中的R6为卤素如Cl时，反应优选以这样的方式进行，即通过喷射或其它适合的方式除去反应产生的卤化氢。 When the starting compound of formula 37 in the R6 is a halogen such as Cl, the reaction is preferably carried out in such a manner that the hydrogen halide generated by the reaction was removed by spraying or other suitable means. 反应可以在约0至100℃下进行，最方便地在接近环境温度(例如约10至40℃)下进行，并且更优选在约20至30℃下进行。 The reaction may be carried out from about 0 to 100 ℃, most conveniently carried out at near ambient temperature (e.g., about 10 to 40 ℃) under, and more preferably at about 20 to 30 ℃ performed. 加入路易斯酸催化剂(例如用于制备R6为Br的式37的三溴化铝)可以促进反应。 Add a Lewis acid catalyst (e.g., R6 is Br for the preparation of aluminum tribromide Formula 37) can facilitate the reaction. 通过本领域技术人员已知的常规方法，包括萃取，蒸馏和结晶来分离式37的产物。 By conventional methods known to those skilled in the art, including extraction, distillation and crystallization of the isolated product of Formula 37. 该方法的进一步细节在实施例14中说明。 Example 14 Further details of the method described in the embodiment.

R6为Cl或Br的式37的起始化合物可以由已经描述的相应的式38的化合物制备。 R6 is Cl or Br, the starting compound of formula 37 may be prepared from the corresponding compound of formula 38 as already described. 通过标准方法，如在适合的溶剂如二氯甲烷中，用磺酰氯(例如对甲苯磺酰氯)和碱如叔胺(例如三乙胺)处理，可以由相应的式38的化合物同样地制备R6为磺酸酯基的式37的起始化合物；该方法的进一步细节在实施例15中说明。 By standard methods, such as in a suitable solvent such as dichloromethane, with a sulfonyl chloride (e.g., p-toluenesulfonyl chloride) and base such as a tertiary amine (e.g. triethylamine) treatment, may be similarly prepared from the corresponding compound of formula 38 R6 sulfonate group as a starting compound of Formula 37; and further details of the method described in Example 15 embodiment.

R6为C1-C4烷氧基或C1-C4卤烷氧基的式4d的吡唑羧酸也可以通过概述于路线21中的方法制备。 R6 is C1-C4 alkoxy or C1-C4 haloalkoxy of pyrazole carboxylic acid of formula (4d) can also outlined in Scheme 21 in the Preparation.

路线21 Route 21 其中R13为C1-C4烷基，而X为离去基团。 Wherein R13 is C1-C4 alkyl, and X is a leaving group.

在该方法中，代替如路线20中所示的被卤化，式38的化合物被氧化成式32a的化合物。 In this method, instead of the compound such as the compound being halogenated as shown in line 20, Formula 38 is oxidized to a formula 32a. 该氧化的反应条件已在路线19中描述过，用于将式37的化合物转化成式32的化合物。 The oxidation reaction conditions already described in Scheme 19 for the conversion of the compound of formula 37 to the compound of formula 32.

然后通过使式32a的化合物在碱存在下与烷基化剂CF3CH2X(39)接触而将其烷基化，形成式32b的化合物。 Then by reacting a compound of formula 32a in the presence of a base with an alkylating agent CF3CH2X (39) contacting the alkylated to form a compound of formula 32b. 在烷基化剂39中，X是亲核反应离去基团，如卤素(例如Br、I)、OS(O)2CH3(甲磺酸酯)、OS(O)2CF3、OS(O)2Ph-p-CH3(对甲苯磺酸酯)等；甲磺酸酯效果良好。 In the alkylating agent 39, X is a nucleophilic reaction leaving group such as halogen (e.g. Br, I), OS (O) 2CH3 (methanesulfonate), OS (O) 2CF3, OS (O) 2Ph- p-CH3 (p-toluenesulfonate) and the like; mesylate good effect. 反应在至少一当量的碱存在下进行。 Reaction is carried out in the presence of at least one equivalent of a base. 适合的碱包括无机碱，如碱金属(如锂、钠或钾)碳酸盐和氢氧化物，以及有机碱，如三乙胺、二异丙基乙胺和1，8-二氮杂二环[5.4.0]十一碳-7-烯。 Suitable bases include inorganic bases, such as alkali metal (such as lithium, sodium or potassium) carbonates and hydroxides, and organic bases such as triethylamine, diisopropylethylamine and 1,8-diazabicyclo [5.4.0] undec-7-ene. 反应通常在溶剂中进行，所述溶剂可以包含醇，如甲醇和乙醇，卤代烷烃，如二氯甲烷，芳族溶剂，如苯、甲苯和氯苯，醚，如四氢呋喃，以及极性非质子溶剂，如乙腈、N，N-二甲基甲酰胺等。 The reaction is usually carried out in a solvent, the solvent may comprise an alcohol, such as methanol and ethanol, halogenated alkanes, such as dichloromethane, aromatic solvents, such as benzene, toluene and chlorobenzene, ethers, such as tetrahydrofuran, and polar aprotic solvent , such as acetonitrile, N, N- dimethylformamide and the like. 醇和极性非质子溶剂优选与无机碱一起使用。 Alcohols and polar aprotic solvent is preferably used together with an inorganic base. 碳酸钾作为碱而乙腈作为溶剂是优选的。 Potassium carbonate as a base and acetonitrile as solvent are preferred. 反应通常在约0至150℃下进行，最通常在室温至100℃下进行。 The reaction is generally at about 0 to 150 ℃ performed, most usually carried out at room temperature to 100 ℃ in. 式32b的产物可以通过常规技术，如萃取而分离。 The product of Formula 32b can be by conventional techniques, such as extraction and separation. 然后可以通过已在路线17中描述过的用于将式32转化成式4d的方法来将式32b的酯转化成式4d的羧酸。 Can then be described in Scheme 17 through 32 for the conversion process of formula of formula (4d) to the ester of formula 32b is converted to a carboxylic acid of formula 4d. 路线21的方法的进一步实验细节在实施例16中说明。 Further experimental details of the method of Scheme 21 is described in Example 16 embodiment.

式38的化合物可以由式33的化合物制备，如路线22所示。 Compounds of formula 38 may be prepared from compounds of formula 33, as shown in Scheme 22.

路线22 Route 22 其中R13为C1-C4烷基。 Wherein R13 is C1-C4 alkyl.

在该方法中，在碱和溶剂存在下使式33的肼化合物与式40的化合物(可以使用富马酸酯或马来酸酯或它们的混合物)接触。 In this method, a base and a solvent in the presence of a compound of formula 33 with a hydrazine compound of formula 40 (which can be used fumarate or maleate or mixtures thereof) in contact. 碱通常为金属醇盐，如甲醇钠、甲醇钾、乙醇钠、乙醇钾、叔丁醇钾、叔丁醇锂等。 The base is typically a metal alkoxide such as sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, lithium tert-butoxide and the like. 相对于式33化合物而言，应使用高于0.5当量的碱，优选为0.9至1.3当量。 Relative to the compound of Formula 33 should be used more than 0.5 equivalents of base, preferably 0.9 to 1.3 equivalents. 应使用高于1.0当量的式40的化合物，优选为1.0至1.3当量。 Use 1.0 equivalents of the compound of formula 40 above, preferably 1.0 to 1.3 equivalents. 可以使用极性质子和极性非质子溶剂，如醇、乙腈、四氢呋喃、N，N-二甲基甲酰胺、二甲基亚砜等。 You can use the polar protic and polar aprotic solvents, such as alcohols, acetonitrile, tetrahydrofuran, N, N- dimethylformamide, dimethyl sulfoxide and the like. 优选的溶剂是醇，如甲醇和乙醇。 Preferred solvents are alcohols such as methanol and ethanol. 特别优选醇与构成富马酸酯或马来酸酯，以及醇盐的醇相同。 Particularly preferred alcohols constituting the fumarate or maleate ester and the alkoxide of the same alcohol. 反应通常通过在溶剂中混合式33的化合物和碱而进行。 Reaction is usually carried out by mixing a solvent and a base 33 of the compound of formula is performed. 可以将混合物加热或冷却至所需的温度，并且在一段时间内加入式40的化合物。 The mixture can be heated or cooled to a desired temperature, and the compound of Formula 40 added over a period of time. 通常反应温度在0℃至所用溶剂的沸点之间。 The reaction temperature is usually between 0 ℃ to the boiling point of the solvent used. 反应可以在高于大气压下进行，以提高溶剂的沸点。 The reaction may be carried out at higher than atmospheric pressure, in order to increase the boiling point of the solvent. 约30至90℃的温度通常是优选的。 A temperature of about 30 to 90 ℃ is generally preferred. 加入的时间可与热传递所允许的一样快。 Time can be added as fast as the heat transfer allows. 通常的加入的时间为1分钟至2小时。 The added time is usually 1 to 2 minutes. 最佳的反应温度和加入的时间随式33和式40的化合物的特性而变。 Optimum reaction temperature and time with the added properties of the compounds of formula 33 and formula 40 becomes. 在加入后，可以将反应混合物在反应温度下放置一段时间。 After addition, the reaction mixture may be placed for some time at the reaction temperature. 取决于反应温度，所需的放置时间可以为0至2小时。 Depending on the reaction temperature, the required standing time may be from 0 to 2 hours. 通常的放置时间是10至60分钟。 The standing time is generally 10-60 minutes. 然后通过加入有机酸，如醋酸等，或无机酸，如盐酸、硫酸等而酸化反应物料。 Then by adding an organic acid, such as acetic acid, or inorganic acids, such as hydrochloric acid, sulfuric acid, etc. The reaction mass is acidified. 取决于反应条件和分离方法，式38的化合物上的-CO2R13官能团可以被水解成-CO2H；例如，在反应混合物中有水存在可以促进这种水解。 Depending on the reaction conditions and separation process, -CO2R13 functional group on the compound of formula 38 may be hydrolyzed to -CO2H; for example, the presence of water can promote such hydrolysis in the reaction mixture. 如果形成羧酸(-CO2H)，可以使用本领域熟知的酯化方法将其转化回-CO2R13，其中R13为C1-C4烷基。 If the formation of the carboxylic acid (-CO2H), using esterification methods can be known in the art to convert it back to -CO2R13, wherein R13 is C1-C4 alkyl. 所需的产物，式38的化合物可以通过本领域技术人员已知的方法，如结晶、萃取或蒸馏而得到分离。 The desired product, a compound of formula 38 may be prepared by those skilled in the known methods, such as crystallization, extraction or distillation to obtain a separation.

应认识到，上述用于制备式I的化合物的一些试剂和反应条件可能与中间体中存在的某些官能团不相容。 It should be recognized that some reagents and reaction conditions described above for the preparation of compounds of formula I may not be compatible with certain functionalities present in the intermediates group. 在这些情况下，在合成中引入保护/脱保护程序或官能团互变将有助于获得所需的产物。 In these cases, the introduction of protection / deprotection procedures or functional group interconversions will help obtain the desired product in the synthesis. 保护基的使用和选择对于化学合成技术人员而言是清楚的(参见，例如，Greene，TW；Wuts，PGMProtective Groups in Organic Synthesis，2nd ed.；Wiley：New York，1991)。 Use and choice of protecting groups for chemical synthesis techniques will be clear to persons (see, e.g., Greene, TW; Wuts, PGMProtective Groups in Organic Synthesis, 2nd ed; Wiley:. New York, 1991). 本领域技术人员将认识到，在某些情况下，在如在任何单个路线中所示引入给定试剂后，可能需要进行未详细描述的其它常规合成步骤，以完成式I的化合物的合成。 Skilled in the art will recognize that, in some cases, after the introduction of a given reagent as shown in any single line, it may be necessary to perform additional routine synthetic steps not described in detail, in order to perfect the compound I of the synthesis. 本领域技术人员还将认识到，为了制备式I的化合物，可能需要将上述路线中所示的步骤以不同于所示的特定顺序的顺序组合进行。 Those skilled in the art will also recognize that, for preparing a compound of formula I, may need to step in the route shown in the order shown in a particular order are different from those carried out.

相信最大限度地使用前面的描述，本领域技术人员能够制备本发明的式I的化合物。 Believe that to maximize the use of the foregoing description, the compounds of formula I of the present invention can be prepared by the skilled person. 因此，以下实施例仅是说明性的，其不以任何方式限制本发明。 Thus, the following examples are illustrative only, it does not in any way limit the present invention. 除了对于色谱溶剂混合物而言或另有说明外，百分比指重量百分比。 In addition to the purposes for chromatographic solvent mixtures or where otherwise indicated, percentages are percentages by weight. 除非另有说明，份和色谱溶剂混合物的百分比是体积比。 Unless otherwise indicated, parts and percentages for chromatographic solvent mixtures are by volume. 1H NMR谱以自四甲基甲硅烷的ppm低磁场报告；s表示单峰，d表示双峰，t表示三重峰，q表示四重峰，m表示多重峰，dd表示双峰的双峰，dt表示三重峰的双峰，br表示宽单峰。 1H NMR spectra were self ppm downfield of tetramethylsilane report; s represents singlet, d represents doublet, t is triplet, q is quartet, m is multiplet, dd doublet of doublet, dt is triplet of doublet, br indicates a broad singlet.

实施例12-[1-乙基-3-三氟甲基吡唑-5-基氨基甲酰基]-3-甲基-N-(1-甲基乙基)苯甲酰胺的制备步骤A：3-甲基-N-(1-甲基乙基)-2-硝基苯甲酰胺的制备将在25ml二氯甲烷中的3-甲基-2-硝基苯甲酸(2.00g，11.0mmol)和三乙胺(1.22g，12.1mmol)溶液冷却至10℃。 Example 12 [1-ethyl-3-trifluoromethyl-pyrazol-5-yl carbamoyl] -3-methyl -N- preparation step (1-methylethyl) benzamide A: methyl -N- (1- methylethyl) -2-nitrobenzamide A solution of 3-methyl-2-nitrobenzoic acid in 25ml of methylene chloride (2.00g, 11.0mmol ) and triethylamine (1.22g, 12.1mmol) solution was cooled to 10 ℃. 小心加入氯甲酸乙酯，形成固体沉淀。 Ethyl chloroformate was carefully added, forming a solid precipitate. 搅拌30分钟后，加入异丙胺(0.94g，16.0mmol)，得到均相溶液。 After stirring for 30 minutes, isopropylamine (0.94g, 16.0mmol), to obtain a homogeneous solution. 将该反应再搅拌1小时，并将其倒入水中，用乙酸乙酯萃取。 The reaction was stirred for 1 hour, and was poured into water, extracted with ethyl acetate. 用水洗涤有机萃取物，用硫酸镁干燥并减压蒸发，产生1.96g所需的中间体，为白色固体，其在126-128℃熔化。 The organic extract was washed with water, dried over magnesium sulfate and evaporated under reduced pressure to produce 1.96g of the desired intermediate as a white solid, melting at 126-128 ℃.

1H NMR(CDCl3)δ1.24(d，6H)，2.38(s，3H)，4.22(m，1H)，5.80(brs，1H)，7.4(m，3H)。 1H NMR (CDCl3) δ1.24 (d, 6H), 2.38 (s, 3H), 4.22 (m, 1H), 5.80 (brs, 1H), 7.4 (m, 3H).

步骤B：2-氨基-3-甲基-N-(1-甲基乙基)苯甲酰胺的制备在5％Pd/C上，40ml乙醇中，于50psi下，将步骤A的2-硝基苯甲酰胺(1.70g，7.6mmol)氢化。 Step B: 2- amino-3-methyl -N- Preparation of (1-methylethyl) benzamide in 5% Pd / C on, 40ml of ethanol at 50psi, a solution of 2-Nitrophenyl Step A benzamide (1.70g, 7.6mmol) hydrogenation. 在停止氢气摄入时，通过Celite硅藻土助滤剂过滤反应物，并用乙醚洗涤Celite。 When hydrogen uptake stopped, washed with diethyl ether Celite reaction was filtered through diatomaceous earth filter aid Celite and. 减压蒸发滤液，得到1.41g标题化合物，该化合物为固体，在149-151℃熔化。 The filtrate was evaporated under reduced pressure to give 1.41g of the title compound, the compound is a solid melting at 149-151 ℃.

1H NMR(CDCl3)δ1.24(dd，6H)，2.16(s，3H)，4.25(m，1H)，5.54(br s，2H)，5.85(br s，1H)，6.59(t，1H)，7.13(d，1H)，7.17(d，1H)。 1H NMR (CDCl3) δ1.24 (dd, 6H), 2.16 (s, 3H), 4.25 (m, 1H), 5.54 (br s, 2H), 5.85 (br s, 1H), 6.59 (t, 1H) , 7.13 (d, 1H), 7.17 (d, 1H).

步骤C：1-乙基-3-三氟甲基吡唑-5-基羧酸的制备在30ml N，N-二甲基甲酰胺中搅拌3-三氟甲基吡唑(5g，37mmol)和粉末状碳酸钾(10g，72mmol)的混合物，滴加碘乙烷(8g，51mmol)到混合物中。 Step C: Preparation of 1-ethyl-3-trifluoromethyl-pyrazol-5-yl-carboxylic acid 3-trifluoromethyl pyrazole was stirred in 30ml N, N- dimethyl formamide (5g, 37mmol) and a mixture of powdered potassium carbonate (10g, 72mmol) and a solution of iodine oxide (8g, 51mmol) to the mixture. 温和放热后，在室温下将反应物搅拌过夜。 After a mild exotherm, the reaction was stirred at room temperature overnight. 反应混合物在100ml乙醚和100ml水间分配。 The reaction mixture was partitioned between 100ml of ether and 100ml of water. 分离乙醚层并用水(3X)和盐水洗涤，用硫酸镁干燥。 The ether layer was separated and washed with water (3X) and brine, dried over magnesium sulfate. 真空中蒸去溶剂得到4g油。 The solvent was evaporated in vacuo to give 4g oil.

在氮气保护下，在干冰/丙酮浴中，3.8g上述油在40ml的四氢呋喃中搅拌，滴加17ml四氢呋喃(43mmol)中的2.5M正丁基锂溶液，将溶液在-78℃下搅拌20分钟。 Under nitrogen, in a dry ice / acetone bath, 3.8g of the above oil in 40ml of tetrahydrofuran was stirred, was added dropwise 17ml of tetrahydrofuran (43mmol) of 2.5M n-butyllithium solution, and the solution was stirred at -78 ℃ 20 分钟. 以中等的速度往搅拌的溶液中通入过量的二氧化碳气10分钟。 At medium speed to a stirred solution leads to an excess of carbon dioxide gas 10 minutes. 加入二氧化碳后，使反应物慢慢达到室温并搅拌过夜。 After addition of carbon dioxide, the reaction was slowly brought to room temperature and stirred overnight. 反应混合物在乙醚(100ml)和0.5N氢氧化钠水溶液(100ml)间分配。 The reaction mixture in diethyl ether (100ml) and 0.5N aqueous sodium hydroxide solution (100ml) partitioned between. 分离碱层，用浓盐酸酸化至pH 2-3。 Base layer was separated, acidified with concentrated hydrochloric acid to pH 2-3. 用乙酸乙酯(100ml)萃取含水混合物，用水和盐水洗涤有机萃取物，并用硫酸镁干燥。 With ethyl acetate (100ml) The aqueous mixture was extracted, and the organic extract was washed with water and brine, and dried over magnesium sulfate. 真空中蒸去溶剂后留下的油状残存物在少量1-氯丁烷中研磨成固体。 After evaporation of the solvent in vacuo the oily residue was left in a small amount of 1-chlorobutane was triturated to a solid. 过滤和干燥后，得到不太纯的1-乙基-3-三氟甲基-吡唑-5-基羧酸样品(1.4g)，为宽熔点固体。 After filtration and drying, to give a less pure 1-ethyl-3-trifluoromethyl - pyrazol-5-yl-carboxylic acid sample (1.4g), a width of the melting point of the solid.

1H NMR(CDCl3)δ1.51(t，3H)，4.68(q，2H)，7.23(s，1H)，9.85(brs，1H)。 1H NMR (CDCl3) δ1.51 (t, 3H), 4.68 (q, 2H), 7.23 (s, 1H), 9.85 (brs, 1H).

步骤D：2-[1-乙基-3-三氟甲基吡唑-5-基氨基甲酰基]-3-甲基-N-(1-甲基乙基)苯甲酰胺的制备将草酰氯(1.2ml，14mmol)加到1-乙基-3-三氟甲基-吡唑-5基羧酸(即步骤C的产物)(0.5g，2.4mmol)在20ml二氯甲烷中搅拌的溶液中。 Step D: 2- [1- ethyl-3-trifluoromethyl-pyrazol-5-yl carbamoyl] -3-methyl -N- Preparation of (1-methylethyl) benzamide Oxalyl chloride (1.2ml, 14mmol) was added 1-ethyl-3-trifluoromethyl - pyrazol-5-yl carboxylic acid (i.e. product of Step C) (0.5g, 2.4mmol) in 20ml dichloromethane was stirred solution. 刚一加入2滴N，N-二甲基甲酰胺，即产生泡沫和气泡。 Just an added 2 drops of N, N- dimethylformamide, which produce foam and bubbles. 反应混合物回流加热1小时，成为黄色溶液。 The reaction mixture was heated under reflux for 1 hour, the solution became yellow. 冷却后，真空除去溶剂，所得残留物溶解于20ml四氢呋喃中。 After cooling, the solvent was removed in vacuo, the resulting residue was dissolved in 20ml of tetrahydrofuran. 添加2-氨基-3-甲基-N-(1-甲基乙基)苯甲酰胺(即步骤B的产物)(0.7g，3.6mol)至搅拌的溶液中，然后滴加N，N-二异丙基乙胺(3ml，17mmol)。 2-amino-3-methyl -N- (1- methylethyl) benzamide (i.e. the product of Step B) (0.7g, 3.6mol) to a stirred solution, followed by dropwise addition of N, N- diisopropylethylamine (3ml, 17mmol). 在室温下搅拌过夜后，反应混合物在乙酸乙酯(100ml)和1N盐酸水溶液(75ml)间分配。 After stirring at room temperature overnight, the reaction mixture was partitioned between ethyl acetate (100ml) and 1N aqueous hydrochloric acid (75ml) Room. 用水和盐水洗涤分离的有机层，用硫酸镁干燥。 The organic layer was separated and washed with water and brine, dried over magnesium sulfate. 真空蒸发得到白色固体残留物，通过闪蒸硅胶柱色谱(2∶1己烷/乙酸乙酯)纯化得到0.5g标题化合物，本发明的化合物，在223-226℃熔化。 Evaporated in vacuo to give a white solid residue by flash silica gel column chromatography (2:1 hexanes / ethyl acetate) to give 0.5g of the title compound, compound of the present invention, melting at 223-226 ℃.

1H NMR(DMSO-d6)δ1.06(d，6H)，1.36(t，3H)，2.45(s，3H)，3.97(m，1H)，4.58(q，2H)，7.43-7.25(m，3H)，7.45(s，1H)，8.05(d，1H)，10.15(s，1H)。 1H NMR (DMSO-d6) δ1.06 (d, 6H), 1.36 (t, 3H), 2.45 (s, 3H), 3.97 (m, 1H), 4.58 (q, 2H), 7.43-7.25 (m, 3H), 7.45 (s, 1H), 8.05 (d, 1H), 10.15 (s, 1H).

实施例2N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-苯基-3-(三氟甲基)-1H-吡唑-5-酰胺的制备步骤A：2-甲基-1-苯基-4-(三氟甲基)-1H-吡唑的制备用冰/水浴将1，1，1-三氟戊烷-2，4-二酮(20.0g，0.130mol)在冰醋酸(60ml)中的溶液冷却至7℃。 2N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] 1- phenyl-3- (trifluoromethyl) -1H- pyrazole -5 - Preparation of amide Step A: 2- methyl-1-phenyl-4- (trifluoromethyl) -1H- pyrazole with an ice / water bath and 1,1,1-trifluoro-pentane -2, 2,4-dione (20.0g, 0.130mol) was cooled in glacial acetic acid (60ml) in to 7 ℃. 在60分钟内滴加苯肼(14.1g，0.130mol)。 Solution of phenylhydrazine (14.1g, 0.130mol) over 60 minutes. 在加入过程中，反应物料温度升至15℃。 During the addition, the reaction mass temperature rose to 15 ℃. 所得的橙色溶液在室温下保持60分钟。 The resulting orange solution was kept at room temperature for 60 minutes. 在浴温65℃的旋转蒸发仪上提馏除去大部分乙酸。 Stripping to remove most of acetic acid at a bath temperature of 65 ℃ on a rotary evaporator. 残留物溶解在二氯甲烷(150ml)中。 The residue was dissolved in dichloromethane (150ml) at. 用碳酸氢钠水溶液(在50ml水中3g)洗涤该溶液。 With aqueous sodium bicarbonate (50ml of water in 3g) and the solution was washed. 分出紫红色有机层，用活性炭(2g)和MgSO4处理，然后过滤。 Purple organic layer was separated, treated with activated carbon (2g) and MgSO4 treatment, and then filtered. 在旋转蒸发仪上除去挥发物。 Removed on a rotary evaporator volatiles. 粗产物由28.0g玫瑰色油组成，其含有～89％所需产物和11％的1-苯基-5-(三氟甲基)-3-甲基吡唑。 The crude product was purified by 28.0g rose oil composition, comprising ~ 89% of the desired product and 11% 1-phenyl-5- (trifluoromethyl) -3-methylpyrazole.

1H NMR(DMSO-d6)δ2.35(s，3H)，6.76(s，1H)，7.6-7.5(m，5H)。 1H NMR (DMSO-d6) δ2.35 (s, 3H), 6.76 (s, 1H), 7.6-7.5 (m, 5H).

步骤B：1-苯基-3-(三氟甲基)-1H-吡唑-5-羧酸的制备将粗2-甲基-1-苯基-4-(三氟甲基)-1H-吡唑(即步骤A的产物)(～89％，50.0g，0.221mol)的样品与水(400ml)和十六烷基三甲基氯化铵(4.00g，0.011mol)混合。 Step B: 1- phenyl-3- (trifluoromethyl) -1H- pyrazole 5-carboxylic acid The crude 2-methyl-1-phenyl-4- (trifluoromethyl) -1H - pyrazole (i.e. the product of Step A) (~ 89%, 50.0g, 0.221mol) sample with water (400ml) and cetyl trimethyl ammonium chloride (4.00g, 0.011mol) and mixed. 混合物加热到95℃。 The mixture was heated to 95 ℃. 以8分钟的间隔，把高锰酸钾以10等份加入。 8-minute intervals, the potassium permanganate was added in 10 equal portions. 在此期间反应物料保持在95-100℃。 During this period the reaction mass was maintained at 95-100 ℃. 在最后一份加入后，该混合物在95-100℃下保持～15分钟，此时紫色，高锰酸钾的颜色消失。 After the last added, the mixture was maintained to 15 minutes at 95-100 ℃, purple color at this time, potassium permanganate disappeared. 在热的时候(～75℃)，通过150～ml粗的玻璃料漏斗中的1cm厚的Celite硅藻土助滤剂过滤反应物料。 When hot (~ 75 ℃), by 150 ~ ml coarse glass frit funnel 1cm thick Celite reaction mass was filtered through Celite filter aid. 滤饼用温水(～50℃)(3×100ml)洗涤。 The filter cake (3 × 100ml) and washed with warm (~ 50 ℃). 用乙醚(2×100ml)萃取合并的滤液和洗液，除去少量黄色的，非水溶性物质。 With ether (2 × 100ml) The combined filtrate and washings were extracted to remove the small amount of yellow, water-insoluble substances. 水层用氮气吹洗除去残留的乙醚。 The aqueous layer was purged with nitrogen to remove residual ether. 通过滴加浓盐酸酸化清亮、无色的碱溶液，直至pH达到～1.3(28g，0.28mol)。 By dropwise addition of concentrated hydrochloric acid clear, colorless alkaline solution, until the pH reached ~ 1.3 (28g, 0.28mol). 在加前三分之二酸的过程中，气体激烈释放。 During the first two-thirds increase in the acid gas intense release. 经过滤收集产品，用水洗涤(3×40ml)，然后在55℃真空中干燥过夜。 The product was collected by filtration, washed with water (3 × 40ml), then dried overnight at 55 ℃ vacuo. 产物含有11.7g白色结晶粉末，经1H NMR检测产物基本纯净。 Product contains 11.7g of white crystalline powder, detected by 1H NMR essentially pure product.

1H NMR(CDCl3)δ7.33(s，1H)，7.4-7.5(m，5H)。 1H NMR (CDCl3) δ7.33 (s, 1H), 7.4-7.5 (m, 5H).

步骤C：1-苯基-3-(三氟甲基)-1H-吡唑-5-酰氯的制备将粗1-苯基-3-(三氟甲基吡唑-5-羧酸(即步骤B的产物)(4.13g，16.1mmol)的样品溶解在二氯甲烷(45ml)中。用草酰氯(1.80ml，20.6mmol)处理该溶液，随后用N，N-二甲基甲酰胺(0.010ml，0.13mmol)处理该溶液。在加入N，N-二甲基甲酰胺催化剂后片刻，开始气体释放。在环境条件下搅拌反应混合物～20分钟，然后加热至回流35分钟。通过在浴温55℃的旋转蒸发仪上提馏反应混合物，除去挥发物。产物由4.43g浅黄色油组成，通过1H NMR观察到的仅有杂质为N，N-二甲基甲酰胺。 Step C: 1- phenyl-3- (trifluoromethyl) -1H- pyrazole 5-carbonyl chloride of crude 1-phenyl-3- (trifluoromethyl pyrazole-5-carboxylic acid (i.e. product of Step B) (4.13g, 16.1mmol) sample was dissolved in dichloromethane (45ml) in. The solution was treated with oxalyl chloride (1.80ml, 20.6mmol), followed by N, N- dimethylformamide ( 0.010ml, 0.13mmol) and the solution treated in the addition of N, N- dimethylformamide after catalyst moment, gas evolution began. The reaction was stirred at ambient conditions the mixture was ~ 20 minutes, then heated to reflux for 35 minutes. By bath stripping the reaction mixture on a rotary evaporator 55 ℃ temperature, the volatiles were removed. The product from 4.43g as a pale yellow oil composition, observed by 1H NMR just impurity N, N- dimethylformamide.

1H NMR(CDCl3)δ7.40(m，1H)，7.42(s，1H)，7.50-7.53(m，4H)。 1H NMR (CDCl3) δ7.40 (m, 1H), 7.42 (s, 1H), 7.50-7.53 (m, 4H).

步骤D：N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-苯基-3-(三氟甲基)-1H-吡唑-5-酰胺的制备用1-苯基-3-(三氟甲基吡唑)-5-酰氯(即步骤C的产物)(0.55g，1.9mmol)处理部分溶解在吡啶(4.0ml)中的3-甲基靛红酸酐(0.30g，1.7mmol)样品。 Step D: N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1-phenyl-3- (trifluoromethyl) -1H- pyrazol - 5- Preparation of 1-phenyl-amide-3- (trifluoromethyl pyrazole) -5- chloride (i.e. the product of Step C) (0.55g, 1.9mmol) was dissolved in pyridine processing section (4.0ml) in 3-methyl-isatoic anhydride (0.30g, 1.7mmol) sample. 混合物被加热至～95℃2小时。 The mixture was heated to ~ 95 ℃ 2 hours. 所得橙色溶液冷却至29℃，然后用异丙铵(1.00g，16.9mmol)处理。 The resulting orange solution was cooled to 29 ℃, and then treated with isopropyl ammonium (1.00g, 16.9mmol). 反应物料放热至39℃。 Exothermic reaction mass to 39 ℃. 再加热至55℃30分钟，即形成许多沉淀。 And then heated to 55 ℃ 30 minutes, i.e., the formation of many precipitate. 反应物料溶解在二氯甲烷(150ml)中。 The reaction mass was dissolved in dichloromethane (150ml) at. 用酸水溶液(5ml浓HCl在45ml水中)，然后用碱水溶液(2g碳酸钠在50ml水中)洗涤该溶液。 With aqueous acid (5ml in 45ml of concentrated HCl in water), and then (2g of sodium carbonate in 50ml of water) and the solution was washed with an aqueous alkali solution. 有机层用MgSO4干燥，过滤，然后在旋转蒸发仪上浓缩。 The organic layer was dried over MgSO4, filtered, and then concentrated on a rotary evaporator. 减至～4ml时，已形成产物结晶。 When reduced to ~ 4ml, already formed product crystallized. 浆液用～10ml乙醚稀释，即有更多的产物沉淀。 The slurry was diluted with ~ 10ml of ether, i.e. more product precipitated. 过滤分离产物，用乙醚(2×10ml)洗涤，然后用水(2×50ml)洗涤。 The product was isolated by filtration, (2 × 10ml) and washed with diethyl ether, and then washed with water (2 × 50ml) and washed. 湿饼在70℃真空中干燥30分钟。 The wet cake was dried in vacuo at 70 ℃ for 30 minutes. 产物，本发明的化合物，由0.52g乳白色的粉末组成，在260-262℃熔化。 The product, the compound of the present invention, by 0.52g milky powder composition, melting at 260-262 ℃.

1H NMR(DMSO-d6)δ1.07(d，6H)，2.21(s，3H)，4.02(octet，1H)，7.2-7.4(m，3H)，7.45-7.6(m，6H)，8.10(d，1H)，10.31(s，1H)。 1H NMR (DMSO-d6) δ1.07 (d, 6H), 2.21 (s, 3H), 4.02 (octet, 1H), 7.2-7.4 (m, 3H), 7.45-7.6 (m, 6H), 8.10 ( d, 1H), 10.31 (s, 1H).

实施例3N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-3-(三氟甲基)-1-[3-(三氟甲基)-2-吡啶基]-1H-吡唑-5-酰胺的制备步骤A：3-三氟甲基-2-[3-(三氟甲基)-1H-吡唑-1-基]吡啶的制备将2-氯-3-三氟甲基吡啶(3.62g，21mmol)，3-三氟甲基吡唑(2.7g，20mmol)和碳酸钾(6.0g，43mmol)的混合物于100℃加热18小时。 EXAMPLE 3N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -3- (trifluoromethyl) -1- [3- (trifluoromethyl) -2-pyridinyl] -1H- pyrazole-5-carboxamide Preparation of Step A: 3- trifluoromethyl-2- [3- (trifluoromethyl) -1H- pyrazol-1-yl] pyridine Preparation of 2-chloro-3-trifluoromethylpyridine (3.62g, 21mmol), a mixture of 3-trifluoromethyl pyrazole (2.7g, 20mmol) and potassium carbonate (6.0g, 43mmol) was heated at 100 ℃ 18 hours. 冷却的混合物加到冰/水(100ml)中。 The cooled mixture was added to ice / water (100ml) in. 混合物用乙醚(100ml)萃取两次，并且用水(100ml)洗涤合并的乙醚萃取液两次。 Mixture was extracted with diethyl ether (100ml) and extracted twice with diethyl ether and the extracts were twice washed with water (100ml) washed with. 用硫酸镁干燥有机层，并且浓缩至油。 The organic layer was dried over magnesium sulfate, and concentrated to an oil. 通过硅胶色谱，用己烷∶乙酸乙酯8∶1至4∶1作为洗脱剂，得到油状标题化合物(3.5g)。 By chromatography on silica gel using hexane: ethyl acetate 8:1 to 4:1 as eluent to give the title compound as an oil (3.5g).

1H NMR(CDCl3)δ6.75(m，1H)，7.5(m，1H)，8.2(m，2H)，8.7(m，1H)。 1H NMR (CDCl3) δ6.75 (m, 1H), 7.5 (m, 1H), 8.2 (m, 2H), 8.7 (m, 1H).

步骤B：3-(三氟甲基)-1-[3-(三氟甲基)-2-吡啶基]-1H-吡唑-5-羧酸的制备将实施例3，步骤A的标题化合物的混合物(3.4g，13mmol)溶解在四氢呋喃(30ml)中，并冷却至-70℃。 Step B: 3- (trifluoromethyl) -1- [3- (trifluoromethyl) -2-pyridinyl] -1H- pyrazole 5-carboxylic acid to 3, Step A, the title Example mixture of compounds (3.4g, 13mmol) was dissolved in tetrahydrofuran (30ml) in, and cooled to -70 ℃. 加入二异丙基酰胺锂(2N在庚烷/四氢呋喃中，(Aldrich)9.5ml，19mmol)，所得的暗色混合物搅拌10分钟。 Was added lithium diisopropylamide (2N in heptane / tetrahydrofuran, (Aldrich) 9.5ml, 19mmol), the resulting dark mixture was stirred for 10 minutes. 干燥的二氧化碳通入到混合物中15分钟。 Dry carbon dioxide passed into the mixture for 15 minutes. 让混合物热至23℃，用水(50ml)和1N氢氧化钠(10ml)处理。 The mixture was allowed to warm to 23 ℃, washed with water (50ml) and 1N sodium hydroxide (10ml) treated. 先用乙醚(100ml)，然后用乙酸乙酯(100ml)萃取含水混合物。 First with diethyl ether (100ml), then with ethyl acetate (100ml) The aqueous mixture was extracted. 水层用6N盐酸酸化至pH1-2，再用二氯甲烷萃取两次。 The aqueous layer was acidified with 6N hydrochloric acid to pH1-2, and extracted twice with dichloromethane. 有机层用硫酸镁干燥，浓缩得到标题化合物(1.5g)。 The organic layer was dried over magnesium sulfate, and concentrated to give the title compound (1.5g).

1H NMR(CDCl3)δ7.6(m，1H)，7.95(m，1H)，8.56(m，1H)，8.9(m，1H)，14.2(br，1H)。 1H NMR (CDCl3) δ7.6 (m, 1H), 7.95 (m, 1H), 8.56 (m, 1H), 8.9 (m, 1H), 14.2 (br, 1H).

步骤C：N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-3-(三氟甲基)-1-[3-(三氟甲基)-2-吡啶基]-1H-吡唑-5-酰胺的制备用三乙胺(0.9ml)处理实施例3，步骤B的标题化合物(0.54g，1.1mmol)，实施例1，步骤B的标题化合物(0.44g，2.4mmol)和BOP氯化物(双(2-氧-噁唑烷基)膦酰氯，0.54g，2.1mmol)在乙腈(13ml)中的混合物。 Step C: N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -3- (trifluoromethyl) -1- [3- (trifluoromethyl ) -2-pyridinyl] -1H- pyrazole-5-carboxamide was prepared with triethylamine (0.9ml) treatment as in Example 3, Step B, the title compound (0.54g, 1.1mmol), Example 1, Step B of Example The title compound (0.44g, 2.4mmol) and BOP chloride (bis (2-oxo - oxazolidinyl) phosphinic chloride, 0.54g, 2.1mmol) in acetonitrile (13ml) in a mixture. 该混合物在密闭的闪烁瓶中摇动18小时。 The mixture was shaken in a closed scintillation vial for 18 hours. 反应物在乙酸乙酯(100ml)和1N盐酸间分配。 The reaction was partitioned between ethyl acetate (100ml) and 1N hydrochloric acid. 乙酸乙酯层相继用1N盐酸(50ml)、1N氢氧化钠(50ml)和饱和氯化钠溶液(50ml)洗涤。 The ethyl acetate layer was washed successively with 1N hydrochloric acid (50ml), 1N sodium hydroxide (50ml) and saturated sodium chloride solution (50ml) and washed. 有机层用硫酸镁干燥，并进行浓缩。 The organic layer was dried over magnesium sulfate, and concentrated. 残留物经硅胶色谱柱，用己烷/乙酸乙酯(5∶1至3∶1)作为洗脱剂。 The residue was subjected to silica gel column chromatography with hexane / ethyl acetate (5:1 to 3:1) as the eluent. 分离到标题化合物(0.43g)，一种本发明的化合物，为白色固体，mp227-230℃。 To isolate the title compound (0.43g), a compound of the present invention, as a white solid, mp227-230 ℃.

1H NMR(CDCl3)δ1.2(m，6H)，4.15(m，1H)，5.9(br d，1H)，7.1(m，1H)，7.2(m，2H)，7.4(s，1H)，7.6(m，1H)，8.15(m，1H)，8.74(m，1H)，10.4(br，1H)。 1H NMR (CDCl3) δ1.2 (m, 6H), 4.15 (m, 1H), 5.9 (br d, 1H), 7.1 (m, 1H), 7.2 (m, 2H), 7.4 (s, 1H), 7.6 (m, 1H), 8.15 (m, 1H), 8.74 (m, 1H), 10.4 (br, 1H).

实施例41-(3-氯-2-吡啶基)-N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]-苯基]-3-(三氟甲基)-1H-吡唑-5-酰胺的制备步骤A：3-氯-2-[3-(三氟甲基)-1H-吡唑-1-基]吡啶的制备将碳酸钾(166.0g，1.2mol)加入到2，3-二氯吡啶(99.0g，0.67mol)和3-(三氟甲基)-吡唑(83g，0.61mol)在干燥N，N-二甲基甲酰胺(300ml)中的混合物中，然后该反应加热至110-125℃ 48小时。 Example 41- (3-chloro-2-pyridinyl) -N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] - phenyl] -3- (trifluoromethyl yl) -1H- pyrazole-5-carboxamide Preparation of Step A: 3- chloro-2- [3- (trifluoromethyl) -1H- pyrazol-1-yl] pyridine Potassium carbonate (166.0g , 1.2mol) was added to 2,3-dichloropyridine (99.0g, 0.67mol) and 3- (trifluoromethyl) - pyrazole (83g, 0.61mol) in dry N, N- dimethylformamide ( 300ml) and the mixture then the reaction was heated to 110-125 ℃ 48 hours. 反应冷却至100℃，并且通过Celite硅藻助滤剂过滤除去固体。 The reaction was cooled to 100 ℃, and the solid was removed by filtration through filter aid Celite diatoms. 大气压下蒸馏除去N，N-二甲基甲酰胺和过量的二氯吡啶。 Was distilled off under atmospheric pressure N, N- dimethylformamide and excess dichloropyridine. 减压(bp139-141℃，7mm)蒸馏产物得到所需的中间体，为清亮的黄色油(113.4g)。 Under reduced pressure (bp139-141 ℃, 7mm) was distilled to give the desired intermediate product as a clear yellow oil (113.4g).

1H NMR(CDCl3)δ6.78(s，1H)，7.36(t，1H)，7.93(d，1H)，8.15(s，1H)，8.45(d，1H)。 1H NMR (CDCl3) δ6.78 (s, 1H), 7.36 (t, 1H), 7.93 (d, 1H), 8.15 (s, 1H), 8.45 (d, 1H).

步骤B：1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备将-30℃干燥四氢呋喃(300ml)中的二异丙基酰胺锂(425mmol)溶液经套管加入到中在-75℃干燥四氢呋喃(700ml)中的3-氯-2-[3-(三氟甲基)-1H-吡唑-1-基]吡啶(即步骤A的产物)(105.0g，425mmol)溶液中。 Step B: 1- (3- chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxylic acid to -30 ℃ dry tetrahydrofuran (300ml) of diisopropyl lithium amide (425mmol) was added via cannula to a solution at -75 ℃ dry tetrahydrofuran (700ml) of 3-chloro-2- [3- (trifluoromethyl) -1H- pyrazol-1-yl] pyridine (i.e. the product of Step A) (105.0g, 425mmol) solution. 深红色溶液搅拌15分钟，此后在-63℃下通入二氧化碳直到溶液变成浅黄色，并且停止放热。 Dark red solution was stirred for 15 minutes, after which at -63 ℃ with carbon dioxide until the solution turned light yellow, and stops heat. 反应再搅拌20分钟，然后用水(20ml)骤冷。 The reaction was stirred for 20 minutes, then washed with water (20ml) quenched. 减压下除去溶剂，反应混合物在乙醚和0.5N氢氧化钠水溶液间分配。 The solvent was removed under reduced pressure, the reaction mixture was partitioned between ether and 0.5N aqueous sodium hydroxide. 用乙醚(3×)洗涤水萃取物，经Celite硅藻土助滤剂过滤除去残留固体，然后酸化至pH约4，在该点形成橙色油。 The extract was washed with water and with ether (3 ×), filtered through Celite diatomaceous earth filter aid to remove residual solids, and then acidified to a pH of about 4, at which point an orange oil formed. 剧烈搅拌该含水混合物并再加入酸以降低pH至2.5-3。 The aqueous mixture was stirred vigorously and then adding an acid to lower the pH to 2.5-3. 橙色油凝结成颗粒固体，经过滤，相继用水和1N盐酸洗涤，并在50℃真空中干燥，得到标题产物，为乳白色固体(130g)。 Orange oil condense into particulate solid was filtered, washed successively with water and 1N hydrochloric acid by, and dried at 50 ℃ vacuo to give the title product as a cream solid (130g). (来自根据类似方法的另一次操作的产物在175-176℃熔化。)1H NMR(DMSO-d6)δ7.61(s，1H)，7.76(dd，1H)，8.31(d，1H)，8.60(d，1H)。 (Product from another run according to a similar method of melting at 175-176 ℃) 1H NMR (DMSO-d6) δ7.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d, 1H).

步骤C：8-甲基-2H-3，1-苯并噁嗪-2，4(1H)-二酮的制备将干燥1，4-二噁烷(50ml)中三氯甲基氯甲酸酯(8ml)溶液滴加到干燥1，4-二噁烷(50ml)中的2-氨基-3-甲基苯甲酸(6g)溶液中，用冰水冷却以保持反应温度低于25℃。 Step C: 8- methyl -2H-3,1- benzoxazine -2,4 (1H) - dione prepared dry 1,4-dioxane (50ml) of trichloromethyl chloroformate ester (8ml) was added dropwise to dry 1,4-dioxane (50ml) of 2-amino-3-methylbenzoic acid (6g) solution, cooled with ice water to keep the reaction temperature below 25 ℃. 滴加期间开始形成白色沉淀物。 A white precipitate began to form during the addition. 反应混合物在室温下搅拌过夜。 The reaction mixture was stirred at room temperature overnight. 过滤除去沉淀固体，用1，4-二噁烷(2×20ml)和己烷(2×15ml)洗涤，并且风干得到6.51g乳白色固体。 The precipitated solid was removed by filtration with 1,4-dioxane (2 × 20ml) and hexane (2 × 15ml) and washed, and air dried to give 6.51g cream solid.

1H NMR(DMSO-d6)δ2.33(s，3H)，7.18(t，1H)，7.59(d，1H)，7.78(d，1H)，11.0(br s，1H)。 1H NMR (DMSO-d6) δ2.33 (s, 3H), 7.18 (t, 1H), 7.59 (d, 1H), 7.78 (d, 1H), 11.0 (br s, 1H).

步骤D：2-[1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-基]-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备将N，N-二甲基甲酰胺(20滴)和草酰氯(67ml，750mmol)以每份约5-ml在约2小时内加入到二氯甲烷(约2L)中的步骤B制得的羧酸产物(146g，500mmol)悬浮液中。 Step D: 2- [1- (3- chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazol-5-yl] -8-methyl -4H-3,1- benzene benzoxazine-4-one A solution of N, N- dimethylformamide (20 drops) and oxalyl chloride (67ml, 750mmol) in each about 5-ml within about 2 hours was added to dichloromethane (ca. 2L) obtained in Step B of carboxylic acid product (146g, 500mmol) suspension. 在加入期间气体剧烈释放。 Vigorous gas released during the addition. 反应混合物在室温下搅拌过夜。 The reaction mixture was stirred at room temperature overnight. 真空下浓缩反应混合物得到粗酰氯，为不透明橙色混合物。 The reaction mixture was concentrated in vacuo to give the crude acid chloride as an opaque orange mixture. 该材料溶解在二氯甲烷中，过滤除去某些固体，然后再浓缩，无进一步纯化下使用。 This material was dissolved in dichloromethane, filtered to remove some solids, and then concentrated under use without further purification. 粗酰氯溶解在乙腈(250ml)中，并加入到乙腈(400ml)中的步骤C的产物的悬浮液中。 The crude acid chloride was dissolved in acetonitrile (250ml), and adding to acetonitrile (400ml) of the product of Step C suspension. 加入吡啶(250ml)，混合物室温下搅拌15分钟，然后升温回流3小时。 Pyridine (250ml), the mixture was stirred at room temperature for 15 minutes, then warmed at reflux for 3 hours. 所得混合物冷却至室温并搅拌过夜得到固体物料。 The resulting mixture was cooled to room temperature and stirred overnight to give a solid material. 再加入乙腈，混合该混合物形成稠浆料。 Acetonitrile was added, the mixture is mixed to form a condensed slurry. 收集固体并用冷乙腈洗涤。 The solid was collected and washed with cold acetonitrile. 风干固体并90℃真空中干燥5小时以得到产量144.8g松软的白色固体。 Air-dried solid was dried in vacuo and 90 ℃ for 5 hours to obtain the yield of 144.8g fluffy white solid.

1H NMR(CDCl3)δ1.84(s，3H)，7.4(t，1H)，7.6(m，3H)，8.0(dd，1H)，8.1(s，1H)，8.6(d，1H)。 1H NMR (CDCl3) δ1.84 (s, 3H), 7.4 (t, 1H), 7.6 (m, 3H), 8.0 (dd, 1H), 8.1 (s, 1H), 8.6 (d, 1H).

步骤E：1-(3-氯-2-吡啶基)-N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-3-(三氟甲基)-1H-吡唑-5-酰胺的制备在室温下将异丙胺(76ml，900mmol)滴加至二氯甲烷(500ml)中的步骤D的苯并噁嗪酮产物(124g，300mmol)的悬浮液中。 Step E: 1- (3- chloro-2-pyridinyl) -N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -3- (trifluoromethyl yl) -1H- pyrazole-5-carboxamide was prepared at room temperature isopropylamine (76ml, 900mmol) was added dropwise to the benzoxazinone product in dichloromethane (500ml) in Step D (124g, 300mmol) in suspension. 在滴加期间，反应混合物的温度上升，悬浮液变稀。 During the dropwise addition, the temperature of the reaction mixture rose, suspension thinning. 然后反应混合物升温至回流1.5小时。 The reaction mixture was then warmed to reflux for 1.5 hours. 形成新的悬浮液。 The formation of new suspension. 反应混合物冷却至室温并且加入乙醚(1.3L)，将该混合物在室温下搅拌过夜。 The reaction mixture was cooled to room temperature and add diethyl ether (1.3L), and the mixture was stirred overnight at room temperature. 用乙醚洗涤收集的固体。 The collected solid was washed with diethyl ether. 风干固体，然后在90℃真空中干燥5小时得到122g标题化合物，本发明的化合物，为松软的白色固体，在194-196℃熔化。 Solid was air-dried, and then dried for 5 hours to obtain 122g of the title compound at 90 ℃ vacuo, compounds of the invention, as a white fluffy solid, melting at 194-196 ℃.

1H NMR(CDCl3)δ1.23(d，6H)，2.21(s，3H)，4.2(m，1H)，5.9(d，1H)，7.2(t，1H)，7.3(m，2H)，7.31(s，1H)，7.4(m，1H)，7.8(d，1H)，8.5(d，1H)，10.4(s，1H)。 1H NMR (CDCl3) δ1.23 (d, 6H), 2.21 (s, 3H), 4.2 (m, 1H), 5.9 (d, 1H), 7.2 (t, 1H), 7.3 (m, 2H), 7.31 (s, 1H), 7.4 (m, 1H), 7.8 (d, 1H), 8.5 (d, 1H), 10.4 (s, 1H).

实施例51-(3-氯-2-吡啶基)-N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]-苯基]-3-(三氟甲基)-1H-吡唑-5-酰胺的另一制备将N，N-二甲基甲酰胺(12滴)和草酰氯(15.8g，124mmol)加入到二氯甲烷(240ml)中的实施例4，步骤B制备的甲酸产物(28g，96mmol)溶液中。 Example 51- (3-chloro-2-pyridinyl) -N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] - phenyl] -3- (trifluoromethyl yl) -1H- pyrazole-5-carboxamido another will be N, N- dimethylformamide (12 drops) and oxalyl chloride (15.8g, 124mmol) was added to dichloromethane Example (240ml) of 4, the carboxylic acid product prepared in Step B (28g, 96mmol) in solution. 反应混合物在室温下搅拌，直至气体释放停止(约1.5小时)。 The reaction mixture was stirred at room temperature, until gas evolution ceased (about 1.5 hours). 真空下浓缩反应混合物得到粗酰氯，为油状，不作进一步纯化直接使用。 The reaction mixture was concentrated in vacuo to give the crude acid chloride as an oil, used without further purification. 粗酰氯溶解在乙腈(95ml)中，并且加入到乙腈(95ml)中的实施例4，步骤C制备的苯并噁嗪-2，4-二酮溶液中。 The crude acid chloride was dissolved in acetonitrile (95ml) in, and added to the acetonitrile in Example (95ml) 4, benzoxazine-2,4-dione prepared in Step C in solution. 在室温下搅拌所得混合物(约30分钟)。 The resulting mixture was stirred at room temperature (about 30 minutes). 加入吡啶(95ml)，混合物加热至约90℃(约1h)。 Pyridine (95ml), the mixture was heated to about 90 ℃ (about 1h). 反应混合物冷却至约35℃，加入异丙胺(25ml)。 The reaction mixture was cooled to about 35 ℃, was added isopropylamine (25ml). 在加入期间反应混合物放热，然后保持在约50℃(约1小时)。 During the addition the reaction mixture exothermed and then was maintained at about 50 ℃ (about 1 hour). 然后将反应混合物倒入冰水中并搅拌。 Then the reaction mixture was poured into ice-water and stirred. 过滤收集所得沉淀物，用水洗涤，在真空中干燥过夜，得到37.5 g标题化合物，一种本发明的化合物，为棕黄色固体。 The resultant was collected by filtration, washed with water and the precipitate was dried in vacuo overnight to give 37.5 g of the title compound, a compound of the present invention, as a tan solid.

1H NMR(CDCl3)δ1.23(d，6H)，2.21(s，3H)，4.2(m，1H)，5.9(d，1H)，7.2(t，1H)，7.3(m，2H)，7.31(s，1H)，7.4(m，1H)，7.8(d，1H)，8.5(d，1H)，10.4(s，1H)。 1H NMR (CDCl3) δ1.23 (d, 6H), 2.21 (s, 3H), 4.2 (m, 1H), 5.9 (d, 1H), 7.2 (t, 1H), 7.3 (m, 2H), 7.31 (s, 1H), 7.4 (m, 1H), 7.8 (d, 1H), 8.5 (d, 1H), 10.4 (s, 1H).

实施例6N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-酰胺的制备步骤A：2-氨基-3-甲基-5-氯苯甲酸的制备将N-氯丁二酰亚胺(13.3g，99.2mmol)加入到N，N-二甲基甲酰胺(50ml)中的2-氨基-3-甲基苯甲酸(Aldrich，15.0g，99.2mmol)溶液中，反应混合物加热至100℃ 30分钟。 EXAMPLE 6N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -3- ( trifluoromethyl) -1H- pyrazole-5-carboxamide Preparation of Step A: 2- amino-3-methyl-5-chloro-benzoic acid N- chlorosuccinimide (13.3g, 99.2mmol ) was added to N, N- dimethylformamide (50ml) of 2-amino-3-methylbenzoic acid (Aldrich, 15.0g, 99.2mmol) in solution, the reaction mixture was heated to 100 ℃ 30 minutes. 停止加热，冷却该反应至室温并保持过夜。 Heating was stopped, the reaction was cooled to room temperature and kept overnight. 然后将反应混合物慢慢倒至冰水(250ml)中以沉淀白色固体。 Then the reaction mixture was slowly poured into ice water (250ml) to precipitate a white solid. 过滤固体并用水洗涤四次，然后溶解在乙酸乙酯(900ml)中。 The solid was filtered and washed with water four times, and then dissolved in ethyl acetate (900ml) in. 用硫酸镁干燥乙酸乙酯溶液，减压下蒸发，乙醚洗涤残留固体，得到所需中间体，为白色固体(13.9g)。 Ethyl acetate solution was dried over magnesium sulfate, evaporated under reduced pressure, the residual solid was washed with diethyl ether to give the desired intermediate as a white solid (13.9g).

1H NMR(DMSO-d6)2.11(s，3H)，7.22(s，1H)，7.55(s，1H)。 1H NMR (DMSO-d6) 2.11 (s, 3H), 7.22 (s, 1H), 7.55 (s, 1H).

步骤B：3-氯-2-[3-(三氟甲基)-1H-吡唑-1-基]吡啶的制备将碳酸钾(166.0g，1.2mol)加入到干燥N，N-二甲基甲酰胺(300ml)中的2，3-二氯吡啶(99.0g，0.67mol)和3-三氟甲基吡唑(83g，0.61mol)混合物中，然后加热该反应至110-125℃ 48小时。 Step B: 3- chloro-2-pyridine [3- (trifluoromethyl) -1H- pyrazol-1-yl] Potassium carbonate (166.0g, 1.2mol) was added to dry N, N- dimethyl formamide (300ml) of 2,3-dichloropyridine (99.0g, 0.67mol) and 3-trifluoromethyl pyrazole (83g, 0.61mol) mixture, and then the reaction was heated to 110-125 ℃ 48 hours. 反应冷却至100℃，通过Celite硅藻土助滤剂过滤反应物除去固体。 The reaction was cooled to 100 ℃, the reaction was filtered to remove solids by Celite diatomaceous earth filter aid. 大气压下蒸馏除去N，N-二甲基甲酰胺和过量的二氯吡啶。 Was distilled off under atmospheric pressure N, N- dimethylformamide and excess dichloropyridine. 减压(bp139-141℃，7mm)蒸馏产物，得到标题化合物，为清亮的黄色油(113.4g)。 Under reduced pressure (bp139-141 ℃, 7mm) The product was distilled to give the title compound as a clear yellow oil (113.4g).

1H NMR(CDCl3)δ6.78(s，1H)，7.36(t，1H)，7.93(d，1H)，8.15(s，1H)，8.45(d，1H)。 1H NMR (CDCl3) δ6.78 (s, 1H), 7.36 (t, 1H), 7.93 (d, 1H), 8.15 (s, 1H), 8.45 (d, 1H).

步骤C：1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备将-30℃的干燥四氢呋喃中(300ml)的二异丙基酰胺锂(425mmol)溶液经套管加入到在-75℃的干燥四氢呋喃(700ml)中的步骤B的吡唑产物(105.0g，425mmol)溶液中。 Step C: Preparation of (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxylic acid 1- to -30 ℃ in dry tetrahydrofuran (300ml) of diisobutyl propyl lithium amide (425mmol) was added via cannula to a solution of the product in dry tetrahydrofuran pyrazole -75 ℃ of (700ml) in Step B (105.0g, 425mmol) solution. 搅拌深红色溶液15分钟后，在-63℃下通入二氧化碳直到溶液变成浅黄色，并且停止放热。 After the deep red solution was stirred for 15 minutes at -63 ℃ with carbon dioxide until the solution became pale yellow and the exotherm stopped. 反应再搅拌20分钟，然后用水(20ml)骤冷。 The reaction was stirred for 20 minutes, then washed with water (20ml) quenched. 在减压下除去溶剂，反应混合物在乙醚和0.5N氢氧化钠水溶液间分配。 The solvent was removed under reduced pressure, the reaction mixture was partitioned between ether and 0.5N aqueous sodium hydroxide. 用乙醚(3×)洗涤水萃取物，经Celite硅藻土助滤剂过滤除去残留固体，然后酸化至pH约4，在该点形成橙色油。 The extract was washed with water and with ether (3 ×), filtered through Celite diatomaceous earth filter aid to remove residual solids, and then acidified to a pH of about 4, at which point an orange oil formed. 剧烈搅拌该含水混合物并再加入酸以降低pH至2.5-3。 The aqueous mixture was stirred vigorously and then adding an acid to lower the pH to 2.5-3. 橙色油凝结成颗粒固体，经过滤，相继用水和1N盐酸洗涤，并在50℃真空中干燥，得到标题产物，为乳白色固体(130g)。 Orange oil condense into particulate solid was filtered, washed successively with water and 1N hydrochloric acid by, and dried at 50 ℃ vacuo to give the title product as a cream solid (130g). (来自根据类似方法的另一操作的产物在175-176℃熔化。)1H NMR(DMSO-d6)δ7.61(s，1H)，7.76(dd，1H)，8.31(d，1H)，8.60(d，1H)。 (According to a similar product from another operating method of melting at 175-176 ℃.) 1H NMR (DMSO-d6) δ7.61 (s, 1H), 7.76 (dd, 1H), 8.31 (d, 1H), 8.60 (d, 1H).

步骤D：6-氯-2-[1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-基]-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备在0-5℃，将乙腈(75ml)中的步骤C的甲酸产物(7.5g，27.0mmol)和三乙胺(3.75ml，27.0mmol)混合物滴加到乙腈(75ml)中的甲磺酰氯(2.2ml，28.3mmol)溶液中。 Step D: 6- chloro-2- [1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazol-5-yl] -8-methyl -4H-3 , the preparation of 1-benzoxazin-4-one at 0-5 ℃, formic acid product in acetonitrile (75ml) in Step C (7.5g, 27.0mmol) and triethylamine (3.75ml, 27.0mmol) mixture was added dropwise to acetonitrile (75ml) of methanesulfonyl chloride (2.2ml, 28.3mmol) in solution. 然后在相继加入试剂过程中，反应温度保持在0℃。 Then in the course of successive addition of reagents, the reaction temperature was maintained at 0 ℃. 搅拌20分钟后，加入步骤A的2-氨基-3-甲基-5-氯苯甲酸(5.1g，27.0mmol)后再继续搅拌5分钟。 After stirring for 20 minutes, Step A was added 2-amino-3-methyl-5-chlorobenzoic acid (5.1g, 27.0mmol) and then stirring was continued for 5 minutes. 然后滴加乙腈(15ml)中的三乙胺(7.5ml，54.0mmol)溶液，反应混合物搅拌45分钟，随后加入甲磺酰氯(2.2ml，28.3mmol)。 Then added dropwise acetonitrile (15ml) of triethylamine (7.5ml, 54.0mmol) added and the reaction mixture was stirred for 45 minutes, followed by addition of methanesulfonyl chloride (2.2ml, 28.3mmol). 然后反应混合物升至室温并搅拌过夜。 The reaction mixture was then warmed to room temperature and stirred overnight. 加入约75ml的水以沉淀5.8g的黄色固体。 About 75ml of water was added to precipitate 5.8g of a yellow solid. 通过萃取从滤液中分离到额外的1g产物，得到总计6.8g标题化合物，为黄色固体。 Isolated by extraction from the filtrate to additional product 1g, to give a total of 6.8g of the title compound as a yellow solid.

1H NMR(CDCl3)δ1.83(s，3H)，7.50(s，1H)，7.53(m，2H)，7.99(m，2H)，8.58(d，1H)。 1H NMR (CDCl3) δ1.83 (s, 3H), 7.50 (s, 1H), 7.53 (m, 2H), 7.99 (m, 2H), 8.58 (d, 1H).

步骤E：N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-酰胺的制备在室温下，将四氢呋喃(10ml)中的异丙胺(2.9ml，34.0mmol)滴加到四氢呋喃(35ml)中的步骤D的苯并噁嗪酮产物(5.0g，11.3mmol)溶液中。 Step E: N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxamide was prepared at room temperature, the tetrahydrofuran (10ml) in isopropylamine (2.9ml, 34.0mmol) was added dropwise to tetrahydrofuran (35ml) benzene in Step D benzoxazine-one product (5.0g, 11.3mmol) in solution. 然后反应混合物升温直到固体溶解，再搅拌5分钟，在硅胶薄层色谱上的点证实反应完成。 Then the reaction mixture was warmed until the solids dissolved, and then stirred for 5 minutes, thin layer chromatography on silica gel point confirmed completion of the reaction. 减压下蒸发四氢呋喃溶剂，采用硅胶色谱纯化残留固体，随后用乙醚/己烷研制，得到标题化合物，本发明的化合物，为固体(4.6g)，在195-196℃熔化。 A tetrahydrofuran solvent was evaporated under reduced pressure, the residual solid was purified by silica gel chromatography, followed by diethyl ether / hexane to give the title compound, compounds of the invention, as a solid (4.6g), melting at 195-196 ℃.

1H NMR(CDCl3)δ1.21(d，6H)，2.17(s，3H)，4.16(m，1H)，5.95(brd，1H)，7.1-7.3(m，2H)，7.39(s，1H)，7.4(m，1H)，7.84(d，1H)，8.50(d，1H)，10.24(br s，1H)。 1H NMR (CDCl3) δ1.21 (d, 6H), 2.17 (s, 3H), 4.16 (m, 1H), 5.95 (brd, 1H), 7.1-7.3 (m, 2H), 7.39 (s, 1H) , 7.4 (m, 1H), 7.84 (d, 1H), 8.50 (d, 1H), 10.24 (br s, 1H).

实施例7N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-酰胺的制备将甲胺(在THF中的2.0M溶液，15ml，30.0mmol)滴加到在四氢呋喃(THF，70ml)中的实施例6，步骤D的苯并噁嗪酮产物(4.50g，10.18mmol)溶液中，在室温下反应混合物搅拌5分钟。 Example 7N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) - Preparation 1H- pyrazole-5 mg of methylamine (2.0M solution in THF, 15ml, 30.0mmol) was added dropwise in tetrahydrofuran (THF, 70ml). 6, Step D of Example benzoxazine ketone product (4.50g, 10.18mmol) and stirred for 5 minutes at room temperature the reaction mixture. 减压下蒸发四氢呋喃溶剂，并且采用硅胶色谱纯化残留固体，得到4.09g标题化合物，本发明的化合物，为白色固体，在185-186℃熔化。 A tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to give 4.09g of the title compound, compounds of the invention, as a white solid, melting at 185-186 ℃.

1H NMR(DMSO-d6)δ2.17(s，3H)，2.65(d，3H)，7.35(d，1H)，7.46(dd，1H)，7.65(dd，1H)，7.74(s，1H)，8.21(d，1H)，8.35(br q，1H)，8.74(d，1H)，10.39(s，1H)。 1H NMR (DMSO-d6) δ2.17 (s, 3H), 2.65 (d, 3H), 7.35 (d, 1H), 7.46 (dd, 1H), 7.65 (dd, 1H), 7.74 (s, 1H) , 8.21 (d, 1H), 8.35 (br q, 1H), 8.74 (d, 1H), 10.39 (s, 1H).

实施例83-氯-N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺的制备步骤A：3-氯-N，N-二甲基-1H-吡唑-1-磺酰胺的制备温度保持在-65℃下，将己烷中的2.5M正丁基锂(472ml，1.18mol)溶液滴加到在-78℃下干燥四氢呋喃(1500ml)中的N-二甲基氨磺酰吡唑(188.0g，1.07mol)溶液中。 Example 83- Chloro -N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxamide Preparation of Step A: 3- chloro -N, N- dimethyl -1H- pyrazol-1-sulfonamide preparation temperature is maintained at -65 ℃, the hexane 2.5M n-butyllithium (472ml, 1.18mol) was added dropwise at -78 ℃ under dry tetrahydrofuran (1500ml) using N- dimethyl sulfamoyl pyrazole (188.0g, 1.07mol) in solution. 加入完成后，反应混合物再保持在-78℃ 45分钟，然后滴加四氢呋喃(120ml)中的六氯乙烷(279g，1.18mol)溶液。 After addition was complete, the reaction mixture was kept at -78 ℃ 45 minutes and then a solution of tetrahydrofuran (120ml) of hexachloroethane (279g, 1.18mol) was added. 该反应混合物在-78℃下保持1小时，升温至-20℃，然后用水(1L)骤冷。 The reaction mixture was kept at -78 ℃ 1 hour warmed to -20 ℃, and then washed with water (1L) quenched. 二氯甲烷(4×500ml)萃取反应混合物；用硫酸镁干燥有机萃取物并浓缩。 Dichloromethane (4 × 500ml) the reaction mixture was extracted; organic extracts were dried over magnesium sulfate and concentrated. 通过硅胶色谱进一步纯化粗产物，用二氯甲烷作为洗脱剂，得到标题产物化合物，为黄色油(160g)。 Was further purified by silica gel chromatography the crude product, with dichloromethane as eluent to give the title product compound as a yellow oil (160g).

1H NMR(CDCl3)δ3.07(d，6H)，6.33(s，1H)，7.61(s，1H)。 1H NMR (CDCl3) δ3.07 (d, 6H), 6.33 (s, 1H), 7.61 (s, 1H).

步骤B：3-氯吡唑的制备将步骤A的氯吡唑产物(160g)滴加到三氟乙酸(290ml)中，室温下反应混合物搅拌1.5小时，然后减压浓缩。 Step B: Preparation of 3-chloro-pyrazol-Chloromethyl pyrazole product of Step A (160g) was added dropwise to trifluoroacetic acid (290ml), and the reaction mixture was stirred at room temperature for 1.5 hours and then concentrated under reduced pressure. 残留物溶解在己烷中，过滤出不溶性固体，并浓缩己烷，得到油状的粗产物。 The residue was dissolved in hexane, the insoluble solid was filtered off, and the hexane was concentrated to afford the crude product as an oil. 粗产物用硅胶色谱进一步纯化，用乙醚/己烷(40∶60)作为洗脱剂，得到标题产物，为黄色油(64.44g)。 The crude product was further purified by chromatography on silica gel eluting with ether / hexane (40:60) as eluent to give the title product as a yellow oil (64.44g).

1H NMR(CDCl3)δ6.39(s，1H)，7.66(s，1H)，9.6(br s，1H)。 1H NMR (CDCl3) δ6.39 (s, 1H), 7.66 (s, 1H), 9.6 (br s, 1H).

步骤C：3-氯-2-(3-氯-1H-吡唑-1-基)吡啶的制备将碳酸钾(147.78g，1.06mol)加入到N，N-二甲基甲酰胺(400ml)中的2，3-二氯吡啶(92.60g，0.629mol)和3-氯吡唑(即步骤B的产物)(64.44g，0.629mol)的混合物中，然后反应混合物加热至100℃ 36小时。 Step C: 3- chloro-2- (3-chloro -1H- pyrazol-1-yl) pyridine Potassium carbonate (147.78g, 1.06mol) was added to N, N- dimethylformamide (400ml) mixture of 2,3-dichloro-pyridine (92.60g, 0.629mol) and 3-chloro-pyrazole (i.e. the product of Step B) (64.44g, 0.629mol), and then the reaction mixture was heated to 100 ℃ 36 hours. 反应混合物冷却至室温并缓慢倒入冰水中。 The reaction mixture was cooled to room temperature and slowly poured into ice water. 过滤沉淀固体并用水洗涤。 The precipitated solid was filtered and washed with water. 固体滤饼溶解在乙酸乙酯中，用硫酸镁干燥并进行浓缩。 The solid cake was dissolved in ethyl acetate, dried over magnesium sulfate and concentrated. 粗固体产物在硅胶上层析，用20％乙酸乙酯/己烷作为洗脱剂，得到标题产物，为白色固体(39.75g)。 The crude solid product was chromatographed on silica gel, eluting with 20% ethyl acetate / hexane as eluent to give the title product as a white solid (39.75g).

1H NMR(CDCl3)δ6.43(s，1H)，7.26(m，1H)，7.90(d，1H)，8.09(s，1H)，8.41(d，1H)。 1H NMR (CDCl3) δ6.43 (s, 1H), 7.26 (m, 1H), 7.90 (d, 1H), 8.09 (s, 1H), 8.41 (d, 1H).

步骤D：3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸将四氢呋喃中的2.0M二异丙基酰胺锂(93ml，186mmol)溶液滴加到在-78℃下干燥四氢呋喃(400ml)中的步骤C的吡唑产物(39.75g，186mmol)溶液中。 Step D: 3- chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid in tetrahydrofuran 2.0M lithium diisopropylamide (93ml, 186mmol) was added dropwise pyrazole product at -78 ℃ under dry tetrahydrofuran (400ml) in Step C (39.75g, 186mmol) solution. 在该琥珀色溶液中通入二氧化碳14分钟，随后该溶液变成浅褐黄色。 In the amber solution with carbon dioxide 14 minutes, then the solution became pale yellow brown. 用1N氢氧化钠水溶液使反应呈碱性，并用乙醚(2×500ml)萃取。 The reaction with 1N aqueous sodium hydroxide solution was made basic and extracted with ether (2 × 500ml). 用6N盐酸酸化含水萃取物，并用乙酸乙酯(3×500ml)萃取。 , And extracted with ethyl acetate (3 × 500ml) and acidified with 6N hydrochloric acid aqueous extract. 用硫酸镁干燥乙酸乙酯萃取物并进行浓缩，得到标题产物，为乳白色固体(42.96g)。 Ethyl acetate extracts were dried over magnesium sulfate and concentrated to give the title product as a cream solid (42.96g). (来自根据类似方法的另一操作的产物在198-199℃熔化。)1H NMR(DMSO-d6)δ6.99(s，1H)，7.45(m，1H)，7.93(d，1H)，8.51(d，1H)。 (According to a similar product from another operating method of melting at 198-199 ℃.) 1H NMR (DMSO-d6) δ6.99 (s, 1H), 7.45 (m, 1H), 7.93 (d, 1H), 8.51 (d, 1H).

步骤E：6-氯-2-[3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-基]-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备在-5℃下，将乙腈(150ml)中的步骤D的甲酸产物(15.0g，58.16mmol)和三乙胺(5.88g，58.16mmol)的混合物滴加到乙腈(150ml)中的甲磺酰氯(6.96g，61.06mmol)溶液中。 Step E: 6- chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazol-5-yl] -8-methyl -4H-3,1- benzo oxazin-4-one was prepared at -5 ℃, the product mixture of formic acid in acetonitrile (150ml) in Step D (15.0g, 58.16mmol) and triethylamine (5.88g, 58.16mmol) was added dropwise to acetonitrile (150ml) of methanesulfonyl chloride (6.96g, 61.06mmol) solution. 然后该反应混合物在0℃搅拌30分钟。 The reaction mixture was then stirred at 0 ℃ 30 minutes. 然后，加入实施例6，步骤A的2-氨基-3-甲基-5-氯苯甲酸(10.79g，58.16mmol)，并再继续搅拌10分钟。 Then, Example 6, Step A 2-amino-3-methyl-5-chlorobenzoic acid (10.79g, 58.16mmol), and stirring was continued for 10 minutes. 然后滴加乙腈中的三乙胺(11.77g，116.5mmol)溶液，同时保持10℃以下的温度。 Acetonitrile was then added dropwise triethylamine (11.77g, 116.5mmol) was added while maintaining the temperature below 10 ℃. 反应混合物在0℃搅拌60分钟，然后加入甲磺酰氯(6.96g，61.06mmol)。 The reaction mixture was stirred at 0 ℃ 60 minutes and then methanesulfonyl chloride (6.96g, 61.06mmol). 随后将反应混合物升温至室温并再搅拌2小时。 Thereafter, the reaction mixture was allowed to warm to room temperature and stirred for 2 hours. 然后浓缩反应混合物，粗产物在硅胶上层析，用二氯甲烷作为洗脱剂，得到标题产物，为黄色固体(9.1g)。 The reaction mixture was then concentrated, the crude product was chromatographed on silica gel using dichloromethane as eluent to give the title product as a yellow solid (9.1g).

1H NMR(CDCl3)δ1.81(s，3H)，7.16(s，1H)，7.51(m，2H)，7.98(d，2H)，8.56(d，1H)。 1H NMR (CDCl3) δ1.81 (s, 3H), 7.16 (s, 1H), 7.51 (m, 2H), 7.98 (d, 2H), 8.56 (d, 1H).

步骤F：3-氯-N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺的制备将异丙胺(4.23g，72.74mmol)加入到四氢呋喃(100ml)中的步骤E的苯并噁嗪酮产物(6.21g，15.21mmol)的溶液中，然后反应混合物加热至60℃，搅拌1小时，然后冷却至室温。 Step F: 3- Chloro -N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridyl ) -1H- pyrazole-5-carboxamido will isopropylamine (4.23g, 72.74mmol) was added to tetrahydrofuran (100ml) in Step E benzoxazinone product (6.21g, 15.21mmol) solution, The reaction mixture was then heated to 60 ℃, stirred for 1 hour, then cooled to room temperature. 在减压下蒸发四氢呋喃溶剂，并且残留固体经硅胶色谱纯化，得到标题化合物，本发明的化合物，为白色固体(5.05g)，在173-175℃熔化。 In a tetrahydrofuran solvent was evaporated under reduced pressure, and the residual solid was purified by silica gel chromatography to give the title compound, compounds of the invention, as a white solid (5.05g), melting at 173-175 ℃.

1H NMR(CDCl3)δ1.23(d，6H)，2.18(s，3H)，4.21(m，1H)，5.97(d，1H)，7.01(m，1H)，7.20(s，1H)，7.24(s，1H)，7.41(d，1H)，7.83(d，1H)，8.43(d，1H)，10.15(br s，1H)。 1H NMR (CDCl3) δ1.23 (d, 6H), 2.18 (s, 3H), 4.21 (m, 1H), 5.97 (d, 1H), 7.01 (m, 1H), 7.20 (s, 1H), 7.24 (s, 1H), 7.41 (d, 1H), 7.83 (d, 1H), 8.43 (d, 1H), 10.15 (br s, 1H).

实施例93-氯-N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺的制备将甲胺(在THF中的2.0M溶液，38ml，77.38mmol)加入到四氢呋喃(50ml)中的实施例8，步骤E的苯并噁嗪酮产物(6.32g，15.47mmol)溶液中，并且反应混合物加热至60℃，搅拌1小时，然后冷却至室温。 Example 93- Chloro -N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -1H- pyrazol - 5- -amide Methylamine (2.0M solution in THF, 38ml, 77.38mmol) in tetrahydrofuran was added to Example 8 (50ml) in step E of the benzoxazinone product (6.32g, 15.47mmol) solution, and the reaction mixture was heated to 60 ℃, stirred for 1 hour, then cooled to room temperature. 在减压下蒸发四氢呋喃溶剂，残留固体经硅胶色谱纯化，得到标题化合物，本发明的化合物，为白色固体(4.57g)，在225-226℃熔化。 The solvent tetrahydrofuran was evaporated under reduced pressure, the solid residue was purified by silica gel chromatography to give the title compound, compounds of the invention, as a white solid (4.57g), melting at 225-226 ℃.

1H NMR(CDCl3)δ2.15(s，3H)，2.93(s，3H)，6.21(d，1H)，7.06(s，1H)，7.18(s，1H)，7.20(s，1H)，7.42(m，1H)，7.83(d，1H)，8.42(d，1H)，10.08(br s，1H)。 1H NMR (CDCl3) δ2.15 (s, 3H), 2.93 (s, 3H), 6.21 (d, 1H), 7.06 (s, 1H), 7.18 (s, 1H), 7.20 (s, 1H), 7.42 (m, 1H), 7.83 (d, 1H), 8.42 (d, 1H), 10.08 (br s, 1H).

实施例103-溴-N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺的制备步骤A：3-溴-N，N-二甲基-1H-吡唑-1-磺酰胺的制备温度保持低于-60℃，将正丁基锂(2.5M在己烷中，105.5ml，0.264mol)滴加到-78℃下干燥四氢呋喃(500ml)中的N-二甲基氨磺酰吡唑(44.0g，0.251mol)溶液中。 Example 103- Bromo -N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxamide Preparation of Step A: 3- bromo -N, N- dimethyl-preparation temperature -1H- pyrazol-1-sulfonamide maintained below -60 ℃, n-butyllithium (2.5M in hexane, 105.5ml, 0.264mol) was added dropwise at -78 ℃ dry tetrahydrofuran (500ml) of N- dimethyl sulfamoyl pyrazole (44.0g, 0.251mol) in solution. 滴加期间形成稠密的固体。 Forming a dense solid during the addition. 滴加完成后，反应混合物再保持15分钟，然后温度保持在-70℃以下，滴加四氢呋喃(150ml)中的1，2-二溴四氯乙烷(90g，0.276mol)溶液。 After the completion of dropwise addition, the reaction mixture was held for 15 minutes and then the temperature was kept below -70 ℃, dropwise tetrahydrofuran (150ml) of 1,2-dibromo-tetrachloroethane (90g, 0.276mol) was added. 反应混合物变成清亮的橙色；再持续搅拌15分钟。 The reaction mixture turned a clear orange; stirring was continued for 15 minutes. 除去-78℃浴并且反应用水(600ml)骤冷。 -78 ℃ bath was removed and the reaction was washed with water (600ml) was quenched. 二氯甲烷(4×)萃取反应混合物，用硫酸镁干燥有机萃取物并进行浓缩。 Dichloromethane (4 ×) reaction mixture was extracted, the organic extracts were dried over magnesium sulfate and concentrated. 粗产物经硅胶色谱进一步纯化，用二氯甲烷/己烷(50∶50)作为洗脱剂，得到标题化合物，为清亮的无色油(57.04g)。 The crude product was further purified by chromatography on silica gel using dichloromethane / hexane (50:50) as eluent to give the title compound as a clear colorless oil (57.04g).

1H NMR(CDCl3)δ3.07(d，6H)，6.44(m，1H)，7.62(m，1H)。 1H NMR (CDCl3) δ3.07 (d, 6H), 6.44 (m, 1H), 7.62 (m, 1H).

步骤B：3-溴吡唑的制备将步骤A的溴吡唑产物(57.04g)缓慢加入到三氟乙酸(70ml)中。 Step B: Preparation of 3-bromo-pyrazol-bromoacetate pyrazole product of Step A (57.04g) was slowly added to trifluoroacetic acid (70ml) in. 室温下搅拌反应混合物30分钟，然后在减压下浓缩。 The reaction mixture was stirred at room temperature for 30 minutes, and then concentrated under reduced pressure. 残留物溶解在己烷中，过滤不溶性固体，蒸发己烷，得到油状粗产物。 The residue was dissolved in hexane, the insoluble solid was filtered, hexane was evaporated to give an oily crude product. 粗产物经用乙酸乙酯/二氯甲烷(10∶90)作为洗脱剂的硅胶色谱进一步纯化，得到油状物。 The crude product was purified by chromatography on silica gel with ethyl acetate / dichloromethane (10:90) as eluent was further purified to give an oil. 将该油溶解在二氯甲烷中，用碳酸氢钠水溶液中和，二氯甲烷(3×)萃取，用硫酸镁干燥并进行浓缩，得到标题产物，为白色固体(25.9g)，mp61-64℃。 The oil was dissolved in dichloromethane, (3 ×) and extracted with aqueous sodium bicarbonate and dichloromethane, dried over magnesium sulfate and concentrated to give the title product as a white solid (25.9g), mp61-64 ℃.

1H NMR(CDCl3)δ6.37(d，1H)，7.59(d，1H)，12.4(br s，1H)。 1H NMR (CDCl3) δ6.37 (d, 1H), 7.59 (d, 1H), 12.4 (br s, 1H).

步骤C：2-(3-溴-1H-吡唑-1-基)-3-氯吡啶的制备将碳酸钾(48.6g，352mmol)加入到干燥N，N-二甲基甲酰胺(88ml)中的2，3-二氯吡啶(27.4g，185mmol)和3-溴吡唑(即步骤B的产物)(25.4g，176mmol)的混合物中，并且反应混合物加热至125℃ 18小时。 Step C: 2- (3- bromo -1H- pyrazol-1-yl) -3-chloro-pyridine Potassium carbonate (48.6g, 352mmol) was added to dry N, N- dimethylformamide (88ml) mixture of 2,3-dichloropyridine (27.4g, 185mmol) and 3-bromo-pyrazole (i.e. the product of Step B) (25.4g, 176mmol) in, and the reaction mixture was heated to 125 ℃ 18 hours. 反应混合物冷却至室温并倒入冰水(800ml)中。 The reaction mixture was cooled to room temperature and poured into ice-water (800ml) in. 形成沉淀。 A precipitate formed. 固体沉淀搅拌1.5小时，过滤并用水(2×100ml)洗涤。 The solid precipitate was stirred for 1.5 hours, filtered and washed with water (2 × 100ml) and washed. 固体滤饼溶解在二氯甲烷中并相继用水、1N盐酸、饱和碳酸氢钠水溶液和盐水洗涤。 The solid cake was dissolved in dichloromethane and washed successively with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine. 然后用硫酸镁干燥有机萃取物并进行浓缩，得到39.9g粉红色固体。 Then the organic extracts were dried over magnesium sulfate and concentrated to give a pink solid 39.9g. 将粗固体产物悬浮在己烷中并剧烈搅拌1小时。 The crude solid product was suspended in hexane and stirred vigorously for 1 hour. 过滤固体，用己烷洗涤并干燥，得到标题产物，为乳白色粉末(30.4g)，经NMR测定达到＞94％纯度。 The solid was filtered, washed with hexane and dried to give the title product as a milky white powder (30.4g), reached by NMR> 94% purity. 该物质不做进一步纯化用于步骤D中。 This material was used without further purification Step D.

1H NMR(CDCl3)δ6.52(s，1H)，7.30(dd，1H)，7.92(d，1H)，8.05(s，1H)，8.43(d，1H)。 1H NMR (CDCl3) δ6.52 (s, 1H), 7.30 (dd, 1H), 7.92 (d, 1H), 8.05 (s, 1H), 8.43 (d, 1H).

步骤D：3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的制备以将温度保持在-71℃以下的速度，将四氢呋喃中的二异丙基酰胺锂溶液滴加到-76℃下干燥四氢呋喃(250ml)中的步骤C的吡唑产物(30.4g，118mmol)溶液中。 Step D: 3- bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid with keeping the temperature below -71 ℃ speed, the tetrahydrofuran diisopropyl pyrazole product of lithium amide was added dropwise at -76 ℃ dry tetrahydrofuran (250ml) in Step C (30.4g, 118mmol) solution. 反应混合物在-76℃下搅拌15分钟，然后通入二氧化碳10分钟，导致升温至-57℃。 The reaction mixture was stirred at -76 ℃ 15 minutes and then purged with carbon dioxide for 10 minutes, resulting in warmed to -57 ℃. 反应混合物升温至-20℃并用水骤冷。 The reaction mixture was allowed to warm to -20 ℃ and quenched with water. 浓缩反应混合物并在水(1L)和乙醚(500ml)中溶解，然后加入氢氧化钠水溶液(1N，20ml)。 The reaction mixture was concentrated and dissolved in water (1L) and ether (500ml), followed by aqueous sodium hydroxide solution (1N, 20ml). 用乙醚洗涤水萃取物并用盐酸酸化。 Washed with ether and the aqueous extract was acidified with hydrochloric acid. 过滤沉淀固体，用水洗涤并干燥，得到标题产物，为棕黄色固体(27.7g)。 The precipitated solid was filtered, washed with water and dried to give the title product as a tan solid (27.7g). (来自根据类似方法的另一操作的产物在200-201℃熔化。)1H NMR(DMSO-d6)δ7.25(s，1H)，7.68(dd，1H)，8.24(d，1H)，8.56(d，1H)。 (According to a similar product from another operating method of melting at 200-201 ℃.) 1H NMR (DMSO-d6) δ7.25 (s, 1H), 7.68 (dd, 1H), 8.24 (d, 1H), 8.56 (d, 1H).

步骤E：2-[3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-基]-6-氯-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备采用类似于实施例6，步骤D的方法，将实施例10，步骤D的吡唑甲酸产物(1.5g，4.96mmol)和2-氨基-3-甲基-5-氯苯甲酸(0.92g，4.96mmol)转化成标题产物，为固体(1.21g)。 Step E: 2- [3- bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazol-5-yl] -6-chloro-8-methyl -4H-3,1- benzo oxazin-4-one was prepared similar to that of Example 6, Step D, Example 10, Step D pyrazole carboxylic acid product (1.5g, 4.96mmol) and 2-amino-3-methyl-5 - chlorobenzoic acid (0.92g, 4.96mmol) is converted to the title product as a solid (1.21g).

1H NMR(CDCl3)δ2.01(s，3H)，7.29(s，1H)，7.42(d，1H)，7.95(d，1H)，8.04(m，1H)，8.25(s，1H)，8.26(d，1H)。 1H NMR (CDCl3) δ2.01 (s, 3H), 7.29 (s, 1H), 7.42 (d, 1H), 7.95 (d, 1H), 8.04 (m, 1H), 8.25 (s, 1H), 8.26 (d, 1H).

步骤F：3-溴-N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺的制备将异丙胺(0.122ml，1.42mmol)加入到四氢呋喃中的步骤E的苯并噁嗪酮产物(0.20g，0.44mmol)溶液中，反应混合物加热至60℃ 90分钟，然后冷却至室温。 Step F: 3- bromo -N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro-2-pyridyl ) -1H- pyrazole-5-carboxamido will isopropylamine (0.122ml, 1.42mmol) was added to tetrahydrofuran Step E benzoxazinone product (0.20g, 0.44mmol) solution and the reaction mixture was heated to 60 ℃ 90 minutes and then cooled to room temperature. 减压下蒸发四氢呋喃溶剂，用乙醚研制残余固体，过滤，并干燥，得到标题化合物，本发明的化合物，为固体(150mg)，mp159-161℃。 A tetrahydrofuran solvent was evaporated under reduced pressure, the residual solid was triturated with ether, filtered and dried to give the title compound, compounds of the invention, as a solid (150mg), mp159-161 ℃.

1H NMR(CDCl3)δ1.22(d，6H)，2.19(s，3H)，4.21(m，1H)，5.99(m，1H)，7.05(m，1H)，7.22(m，2H)，7.39(m，1H)，7.82(d，1H)，8.41(d，1H)。 1H NMR (CDCl3) δ1.22 (d, 6H), 2.19 (s, 3H), 4.21 (m, 1H), 5.99 (m, 1H), 7.05 (m, 1H), 7.22 (m, 2H), 7.39 (m, 1H), 7.82 (d, 1H), 8.41 (d, 1H).

实施例113-溴-N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺的制备将甲胺(在THF中的2.0M溶液，0.514ml，1.02mmol)加入到四氢呋喃中的实施例10，步骤E的苯并噁嗪酮产物(0.20g，0.44mmol)溶液中，反应混合物加热至60℃ 90分钟，然后冷却至室温。 Example 113- Bromo -N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -1H- pyrazol - 5- -amide Methylamine (2.0M solution in THF, 0.514ml, 1.02mmol) in tetrahydrofuran was added to Example 10, Step E benzoxazinone product (0.20g, 0.44mmol) solution The reaction mixture was heated to 60 ℃ 90 minutes and then cooled to room temperature. 减压下蒸发四氢呋喃溶剂，用乙醚研制残留固体，过滤，并干燥得到标题化合物，本发明的化合物，为固体(40mg)，mp162-164℃。 A tetrahydrofuran solvent was evaporated under reduced pressure, the residual solid was triturated with ether, filtered and dried to give the title compound, compounds of the invention, as a solid (40mg), mp162-164 ℃.

1H NMR(CDCl3)δ2.18(s，3H)，2.95(s，3H)，6.21(m，1H)，7.10(s，1H)，7.24(m，2H)，7.39(m，1H)，7.80(d，1H)，8.45(d，1H)。 1H NMR (CDCl3) δ2.18 (s, 3H), 2.95 (s, 3H), 6.21 (m, 1H), 7.10 (s, 1H), 7.24 (m, 2H), 7.39 (m, 1H), 7.80 (d, 1H), 8.45 (d, 1H).

下面的实施例12说明了另一种制备3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的方法，通过实施例8和9所述的进一步的步骤，该化合物可用于制备，例如，3-氯-N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺和3-氯-N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺。 The following Example 12 illustrates an alternative method for the preparation of 3-chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid, by implementing further described in Example 8 and 9 step, the compound can be used to prepare, for example, 3-chloro -N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- ( 3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxamide and 3-chloro -N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1 - (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxamide.

实施例123-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的制备步骤A：2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷羧酸乙酯(另一个命名是1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-羧酸乙酯)的制备在装有机械搅拌器、温度计、加液漏斗、回流冷凝器和氮气入口的2-L四颈烧瓶中装入无水乙醇(250ml)和乙氧基钠的乙醇溶液(21％，190ml，0.504mol)。 Example 123- chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid Step A: 2- (3- chloro-2-pyridinyl) -5-oxo - 3- pyrazolidine-carboxylate (another name is 1- (3-chloro-2-pyridinyl) -3-pyrazolidinone-5-carboxylate) prepared equipped with a mechanical stirrer, thermometer, addition funnel, reflux condenser and nitrogen inlet 2-L four-necked flask was charged with dry ethanol (250ml) and a solution of sodium ethoxide in ethanol (21%, 190ml, 0.504mol). 混合物加热至约83℃回流。 The mixture was heated to reflux for about 83 ℃. 然后用3-氯-2(1H)-吡啶酮腙(pyridinone hydrazone)(68.0g，0.474mol)处理混合物。 Then 3-chloro -2 (1H) - pyridinone hydrazone (pyridinone hydrazone) (68.0g, 0.474mol) processing the mixture. 混合物再加热至回流5分钟。 The mixture was then heated to reflux for 5 minutes. 然后用马来酸二乙酯(88.0ml，0.544mol)滴加处理黄色浆料5分钟。 Then diethyl maleate (88.0ml, 0.544mol) was treated dropwise yellow slurry 5 minutes. 在滴加期间，回流速度显著上升。 During the dropwise addition, and the reflux rate increased significantly. 在结束滴加时，所有起始物质都已溶解。 At the end of the dropwise addition, all of the starting material had dissolved. 所得橘红色溶液回流10分钟。 The resulting orange solution was refluxed for 10 minutes. 然后冷却至65℃，用冰醋酸(50.0ml，0.873mol)处理反应混合物。 Then cooled to 65 ℃, the reaction mixture was treated with glacial acetic acid (50.0ml, 0.873mol). 形成沉淀。 A precipitate formed. 用水(650ml)稀释混合物，使得沉淀溶解。 Washed with water (650ml) the mixture was diluted such that the precipitate dissolved. 橙色溶剂在冰浴中冷却。 Orange solvent cooled in an ice bath. 产物在28℃开始沉淀。 The product began to precipitate at 28 ℃. 浆料置于约2℃ 2小时。 Slurry to about 2 ℃ 2 hours. 产物经过滤分离，用含水乙醇(40％，3×50ml)洗涤，然后在过滤器上风干约1小时。 The product was isolated by filtration, (40%, 3 × 50ml) and washed with aqueous ethanol, and then air-dried on the filter for about 1 hour. 得到标题化合物，为高度结晶，淡橙色粉末(70.3g，55％收率)。 To give the title compound as a highly crystalline, light orange powder (70.3g, 55% yield). 经1H NMR检测无显著杂质。 By 1H NMR detected no significant impurities.

1H NMR(DMSO-d6)δ1.22(t，3H)，2.35(d，1H)，2.91(dd，1H)，4.20(q，2H)，4.84(d，1H)，7.20(dd，1H)，7.92(d，1H)，8.27(d，1H)，10.18(s，1H)。 1H NMR (DMSO-d6) δ1.22 (t, 3H), 2.35 (d, 1H), 2.91 (dd, 1H), 4.20 (q, 2H), 4.84 (d, 1H), 7.20 (dd, 1H) , 7.92 (d, 1H), 8.27 (d, 1H), 10.18 (s, 1H).

步骤B：3-氯-1-(3-氯-1-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯(或者命名为1-(3-氯-2-吡啶基)-3-氯-2-吡唑啉-5-羧酸乙酯)的制备将乙腈(1000ml)、2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷羧酸乙酯(即步骤A的产物)(91.0g，0.337mol)和磷酰氯(35.0ml，0.375mol)装入装有机械搅拌器、温度计、回流冷凝器和氮气入口的2-L的四颈烧瓶中。 Step B: 3- chloro-1- (3-chloro-1-pyridyl) -4,5-dihydro -1H- pyrazole-5-carboxylate (or named as 1- (3-chloro-2 - pyridin-yl) -3-chloro-2-pyrazoline-5-carboxylate) A mixture of acetonitrile (1000ml), 2- (3- chloro-2-pyridinyl) -5-oxo-3-pyridine oxazolidine carboxylate (i.e. product of Step A) (91.0g, 0.337mol) and phosphorus oxychloride (35.0ml, 0.375mol) filled with a mechanical stirrer, thermometer, reflux condenser and nitrogen inlet 2-L four-necked flask. 一加入磷酰氯，混合物即自身放热从22℃至25℃并形成沉淀。 An added phosphorus oxychloride, a mixture that is self-heating from 22 ℃ to 25 ℃ and the formation of precipitation. 淡黄色浆料加热至83℃回流35分钟，沉淀即溶解。 Pale yellow slurry was heated to reflux for 83 ℃ 35 minutes the precipitate that is dissolved. 所得橙色溶液回流45分钟，该溶液即变成青绿色。 The resulting orange solution was refluxed for 45 minutes, the solution was then become turquoise. 用蒸馏头替代回流冷凝器，并且蒸馏除去650ml溶剂。 Alternatively reflux condenser with a distillation head, and the solvent was removed by distillation 650ml. 在装有机械搅拌器的另一个2-L四颈烧瓶中装入碳酸氢钠(130g，1.55mol)和水(400ml)。 Load sodium bicarbonate (130g, 1.55mol) and water (400ml) equipped with a mechanical stirrer, another 2-L four-necked flask. 在15分钟时间内，将浓缩的反应混合物加入到碳酸氢钠浆料中。 Within 15 minutes, the reaction mixture was added to the concentrated slurry of sodium bicarbonate. 将所得到的两相混合物剧烈搅拌20分钟，此时气体释放停止。 The two-phase mixture was vigorously stirred for 20 minutes at which time gas evolution ceased. 用二氯甲烷(250ml)稀释混合物，然后搅拌50分钟。 The mixture was diluted with dichloromethane (250ml), then stirred for 50 minutes. 用Celite545硅藻土助滤剂(11g)处理混合物，然后过滤除去黑色的、焦油状的物质，该物质抑制相分离。 Processing Celite545 diatomaceous earth filter aid (11g) the mixture was then filtered to remove a black, tarry substance that inhibit phase separation. 从滤液慢慢地分离成不同的相开始，用二氯甲烷(200ml)和水(200ml)稀释之，并用更多的Celite545(15g)处理之。 Isolated from the filtrate slowly into different phases started, diluted with dichloromethane (200ml) and water (200ml), and treated with more Celite545 (15g) Treatment of. 过滤混合物，滤液转入分离漏斗。 The mixture was filtered, the filtrate was transferred to a separatory funnel. 分离出更重的、深绿色有机层。 Isolated heavier, deep green organic layer. 再过滤碎层(rag layer)(50ml)，然后将其加入到有机层中。 Refiltered broken layer (rag layer) (50ml), then added to the organic layer. 用硫酸镁(30g)和硅胶(12g)处理有机溶液(800ml)，磁力搅拌浆料30分钟。 With magnesium sulfate (30g) and silica gel (12g) treating the organic solution (800ml), the slurry was stirred magnetically for 30 minutes. 过滤浆料以除去已变成深蓝绿色的硫酸镁和硅胶。 The slurry was filtered to remove the magnesium sulfate has become a dark blue-green and silica gel. 用二氯甲烷(100ml)洗涤滤饼。 (100ml) The filter cake was washed with dichloromethane. 滤液在旋转蒸发仪上浓缩。 The filtrate was concentrated on a rotary evaporator. 产物由黑琥珀色油(93.0g，93％收率)组成。 The product from black amber oil (93.0g, 93% yield) composition. 经1H NMR观测到的杂质仅有1％起始物质和0.7％的乙腈。 By 1H NMR observed only 1% of the starting material impurities and 0.7% acetonitrile.

1H NMR(DMSO-d6)δ1.15(t，3H)，3.26(dd，1H)，3.58(dd，1H)，4.11(q，2H)，5.25(dd，1H)，7.00(dd，1H)，7.84(d，1H)，8.12(d，1H)。 1H NMR (DMSO-d6) δ1.15 (t, 3H), 3.26 (dd, 1H), 3.58 (dd, 1H), 4.11 (q, 2H), 5.25 (dd, 1H), 7.00 (dd, 1H) , 7.84 (d, 1H), 8.12 (d, 1H).

步骤C：3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸乙酯(或者命名为1-(3-氯-2-吡啶基)-3-氯吡唑-5-羧酸乙酯)的制备在装有机械搅拌器、温度计、回流冷凝器和氮气入口的2-L四颈烧瓶中装入3-氯-1-(3-氯-1-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯(即步骤B的产物)(95％纯，99.5g，0.328mol)，乙腈(1000ml)和硫酸(98％，35.0ml，0.661mol)。 Step C: 3- chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylate (or named as 1- (3-chloro-2-pyridinyl) -3- chloro-pyrazole-5-carboxylate) prepared was charged with 3-chloro-equipped with a mechanical stirrer, thermometer, reflux condenser and nitrogen inlet 2-L four-necked flask -1- (3-chloro-1 - pyridyl) -4,5-dihydro -1H- pyrazole-5-carboxylate (i.e. product of Step B) (95% pure, 99.5g, 0.328mol), acetonitrile (1000ml) and sulfuric acid (98 %, 35.0ml, 0.661mol). 一加入硫酸，混合物即自身放热从22℃至35℃。 An addition of sulfuric acid, a mixture that is self-heating from 22 ℃ to 35 ℃. 在搅拌几分钟后，过硫酸钾(140g，0.518mol)处理混合物。 After stirring for a few minutes, potassium persulfate (140g, 0.518mol) processing the mixture. 浆料加热至84℃回流4.5小时。 Slurry was heated to 84 ℃ reflux for 4.5 hours. 将所得橙色浆料在仍温(50-65℃)时过滤，除去细小的白色沉淀。 The resulting orange slurry while still warm (50-65 ℃) when filtered to remove a fine white precipitate. 乙腈(50ml)洗涤滤饼。 Acetonitrile (50ml) and washed filter cake. 滤液在旋转蒸发仪上浓缩至约500ml。 The filtrate was concentrated to about 500ml on a rotary evaporator. 在装有机械搅拌器的另一个2-L四颈烧瓶中装入水(1250ml)。 Filled with water (1250ml) equipped with a mechanical stirrer, another 2-L four-necked flask. 在约5分钟时间内，将该浓缩的反应物料加入到水中。 In about 5 minutes, the reaction mass was added to the concentrated water. 经过滤分离产物，用含水乙腈(25％，3×125ml)洗涤，用水(100ml)洗涤一次，然后在室温下真空干燥过夜。 The product was isolated by filtration, washed with aqueous acetonitrile (25%, 3 × 125ml) and washed with water (100ml) and washed once, and then dried in vacuo overnight at room temperature. 产物由结晶橙色粉末(79.3g，82％收率)组成。 The product crystallized from an orange powder (79.3g, 82% yield) composition. 经1H NMR观测到的杂质仅有约1.9％的水和0.6％的乙腈。 Observed by 1H NMR impurities only about 1.9% water and 0.6% acetonitrile.

1H NMR(DMSO-d6)δ1.09(t，3H)，4.16(q，2H)，7.31(s，1H)，7.71(dd，1H)，8.38(d，1H)，8.59(d，1H)。 1H NMR (DMSO-d6) δ1.09 (t, 3H), 4.16 (q, 2H), 7.31 (s, 1H), 7.71 (dd, 1H), 8.38 (d, 1H), 8.59 (d, 1H) .

步骤D：3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸(或者命名为1-(3-氯-2-吡啶基)-3-氯吡唑-5-羧酸)的制备在装有机械搅拌器、温度计和氮气入口的1-L四颈烧瓶中装入3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸乙酯(即步骤C的产物)(97.5％纯，79.3g，0.270mol)、甲醇(260ml)、水(140ml)和氢氧化钠片(13.0g，0.325mol)。 Step D: 3- chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid (or named as 1- (3-chloro-2-pyridinyl) -3-chloro-pyrazol oxazole-5-carboxylic acid) Preparation of 3-chloro charged equipped with a mechanical stirrer, thermometer, and nitrogen inlet 1-L four-necked flask -1- (3-chloro-2-pyridinyl) -1H- pyrazol oxazole-5-carboxylate (i.e. product of Step C) (97.5% pure, 79.3g, 0.270mol), methanol (260ml), water (140ml) and sodium hydroxide pellets (13.0g, 0.325mol). 一加入氢氧化钠，混合物即自身放热从22℃至35℃，并且起始物质开始溶解。 A solution of sodium hydroxide, a mixture that is self-heating from 22 ℃ to 35 ℃, and the starting material began to dissolve. 在环境条件下搅拌45分钟后，所有起始物质都已溶解。 Was stirred at ambient conditions for 45 minutes, all the starting material had dissolved. 所得深橘红-褐色溶液在旋转蒸发仪上浓缩至约250ml。 The resulting dark orange - brown solution was concentrated to about 250ml on a rotary evaporator. 然后浓缩的反应混合物用水(400ml)稀释。 The reaction mixture was washed with water and then concentrated (400ml) was diluted. 用乙醚(200ml)萃取含水溶液。 With diethyl ether (200ml) and extracted aqueous solution. 将水层转移至装有磁力搅拌器的1-L锥形瓶中。 The aqueous layer was equipped with a magnetic stirrer, transferred to a 1-L Erlenmeyer flask. 溶液用浓盐酸(36.0g，0.355mol)滴加处理约10分钟。 Solution (36.0g, 0.355mol) was treated dropwise with concentrated hydrochloric acid for about 10 minutes. 经过滤分离产物，用水(2×200ml)使其再成为浆料，用水(100ml)覆盖洗涤(cover wash)一次，然后在过滤器上风干1.5小时。 The product was isolated by filtration, washed with water (2 × 200ml) it was reslurried with water (100ml) and washed cover (cover wash) once, and then air-dried on the filter for 1.5 hours. 产物由结晶淡褐色粉末(58.1g，83％收率)组成。 The product crystallized as a pale brown powder from (58.1g, 83% yield) composition. 经1H NMR观测到的杂质仅有约0.7％的乙醚。 By 1H NMR observed that only about 0.7% of impurities ether.

1H NMR(DMSO-d6)δ7.20(s，1H)，7.68(dd，1H)，8.25(d，1H)，8.56(d，1H)，13.95(br s，1H)。 1H NMR (DMSO-d6) δ7.20 (s, 1H), 7.68 (dd, 1H), 8.25 (d, 1H), 8.56 (d, 1H), 13.95 (br s, 1H).

下面的实施例13说明3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的另一制备，通过实施例10和11所述的进一步的步骤，该化合物可用于制备，例如，3-溴-N-[4-氯-2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺和3-溴-N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-1H-吡唑-5-酰胺。 The following Example 13 illustrates the 3-bromo-1- (3-chloro-2-pyridinyl) -1H- another pyrazole 5-carboxylic acid, through the implementation of a further step 10 and described in Example 11, The compound may be used to prepare, for example, 3-bromo--N- [4- chloro-2-methyl-6 - [[(1-methylethyl) amino] carbonyl] phenyl] -1- (3-chloro- 2-pyridinyl) -1H- pyrazole-5-carboxamide and 3-bromo -N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1- (3 - chloro-2-pyridinyl) -1H- pyrazole-5-carboxamide.

实施例133-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸的制备步骤A1：使用三溴氧化磷制备3-溴-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯(或者命名为1-(3-氯-2-吡啶基)-3-溴-2-吡唑啉-5-羧酸乙酯)在装有机械搅拌器、温度计、回流冷凝器和氮气入口的1-L四颈烧瓶中装入乙腈(400ml)、2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷羧酸乙酯(即实施例12，步骤A的产物)(50.0g，0.185mol)和三溴氧化磷(34.0g，0.119mol)。 Example 133- bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid Step A1: Preparation of a three-bromo-phosphorus oxide of 3-bromo-1- (3-chloro - 2-pyridyl) -4,5-dihydro -1H- pyrazole-5-carboxylate (or named as 1- (3-chloro-2-pyridinyl) -3-bromo-2-pyrazoline 5-carboxylate) equipped with a mechanical stirrer, thermometer, reflux condenser and nitrogen inlet 1-L four-necked flask was charged with acetonitrile (400ml), 2- (3- chloro-2-pyridinyl) -5- oxo-3-pyrazolidine-carboxylate (i.e., Example 12, the product of Step A) (50.0g, 0.185mol) and phosphorus oxybromide (34.0g, 0.119mol). 橙色浆料加热至83℃回流超过20分钟。 83 ℃ orange slurry was heated to reflux over 20 minutes. 将所得的混浊的、橙色溶液回流75分钟，此时形成稠的棕黄色结晶沉淀。 The orange turbid solution was refluxed for 75 minutes, then the formation of a thick brown crystalline precipitate. 用蒸馏头替代回流冷凝器，并且收集混浊的无色馏出液(300ml)。 Alternatively reflux condenser with a distillation head, and collecting cloudy colorless distillate (300ml). 在装有机械搅拌器的另一个1-L四颈瓶中装入碳酸氢钠(45g，0.54mol)和水(200ml)。 Equipped with a mechanical stirrer, another 1-L four-necked flask was charged with sodium bicarbonate (45g, 0.54mol) and water (200ml). 在5分钟的时间内将浓缩的反应混合物加入到碳酸氢钠浆料中。 Within 5 minutes the reaction mixture was added to the concentrated slurry of sodium bicarbonate. 所得的两相混合物剧烈搅拌5分钟，此时气体释放停止。 The resulting two-phase mixture was stirred vigorously for 5 minutes at which time gas evolution ceased. 用二氯甲烷(200ml)稀释混合物，然后搅拌75分钟。 The mixture was diluted with dichloromethane (200ml), followed by stirring for 75 minutes. 用5g的Celite545硅藻土助滤剂处理混合物，过滤除去褐色的、焦油状物质。 5g of Celite545 with diatomaceous earth filter aid mixture is treated and filtered to remove a brown, tarry substance. 将滤液转移入分液漏斗。 The filtrate was transferred into a separatory funnel. 分离出褐色的有机层(400ml)，并且然后用硫酸镁(15g)和DarcoG60活性炭(2.0g)处理。 The organic layer was separated brown (400ml), and then dried over magnesium sulfate (15g) and DarcoG60 activated carbon (2.0g) processing. 所得浆料磁力搅拌15分钟，然后过滤除去硫酸镁和活性炭。 The resulting slurry was magnetically stirred for 15 minutes and then filtered to remove magnesium sulfate and charcoal. 用硅胶(3g)处理绿色的滤液并搅拌几分钟。 The green filtrate was treated with silica gel (3g) and stirred for several minutes. 过滤除去深蓝绿色硅胶，在旋转蒸发仪上浓缩滤液。 Dark blue green silica gel was removed by filtration, the filtrate was concentrated on a rotary evaporator. 产物由淡琥珀色油(58.6g，95％收率)组成，在放置后结晶。 The product from light amber oil (58.6g, 95% yield) composed of the crystallized on standing. 经1H NMR观测到的杂质仅有0.3％的乙腈。 Observed by 1H NMR impurity only 0.3% acetonitrile.

1H NMR(DMSO-d6)δ1.15(t，3H)，3.29(dd，1H)，3.60(dd，1H)，4.11(q，2H)，5.20(dd，1H)，6.99(dd，1H)，7.84(d，1H)，8.12(d，1H)。 1H NMR (DMSO-d6) δ1.15 (t, 3H), 3.29 (dd, 1H), 3.60 (dd, 1H), 4.11 (q, 2H), 5.20 (dd, 1H), 6.99 (dd, 1H) , 7.84 (d, 1H), 8.12 (d, 1H).

步骤A2：使用五溴化磷制备3-溴-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯在装有机械搅拌器、温度计、回流冷凝器和氮气入口的1-L四颈烧瓶中装入乙腈(330ml)、2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷羧酸乙酯(即实施例12，步骤A的产物)(52.0g，0.193mol)和五溴化磷(41.0g，0.0952mol)。 Step A2: Preparation of 3 using phosphorus pentabromide bromo-1- (3-chloro-2-pyridinyl) -4,5-dihydro -1H- pyrazole-5-carboxylate equipped with a mechanical stirrer , thermometer, reflux condenser and nitrogen inlet 1-L four-necked flask was charged with acetonitrile (330ml), 2- (3- chloro-2-pyridinyl) -5-oxo-3-pyrazolidine-carboxylate (i.e., Example 12, the product of Step A) (52.0g, 0.193mol) and phosphorus pentabromide (41.0g, 0.0952mol). 橙色浆料加热至84℃回流20分钟。 Orange slurry was heated to reflux for 84 ℃ 20 minutes. 将所得的砖红色混合物回流90分钟，此时形成稠的棕黄色结晶沉淀。 The resulting brick-red mixture was refluxed for 90 minutes at which time the formation of a thick brown crystalline precipitate. 用蒸馏头替代回流冷凝器，并且收集混浊的无色馏出液(220ml)。 Alternatively reflux condenser with a distillation head, and collecting cloudy colorless distillate (220ml). 在装有机械搅拌器的另一个1-L四颈瓶中装入碳酸氢钠(40g，0.48mol)和水(200ml)。 Equipped with a mechanical stirrer, another 1-L four-necked flask was charged with sodium bicarbonate (40g, 0.48mol) and water (200ml). 在5分钟的时间内将浓缩的反应混合物加入到碳酸氢钠浆料中。 Within 5 minutes the reaction mixture was added to the concentrated slurry of sodium bicarbonate. 将所得的两相混合物剧烈搅拌10分钟，此时气体释放停止。 The two-phase mixture was stirred vigorously for 10 minutes at which time gas evolution ceased. 用二氯甲烷(200ml)稀释混合物，然后搅拌10分钟。 The mixture was diluted with dichloromethane (200ml), then stirred for 10 minutes. 用Celite545硅藻土助滤剂(5g)处理混合物，然后过滤除去紫色的、焦油状物质。 With Celite545 diatomaceous earth filter aid (5g) processing the mixture, and then filtered to remove a purple, tarry substance. 用二氯甲烷(50ml)洗涤滤饼。 (50ml) cake was washed with dichloromethane. 将滤液转移入分液漏斗。 The filtrate was transferred into a separatory funnel. 分离出紫红色有机层(400ml)，然后用硫酸镁(15g)和DarcoG60活性炭(2.2g)处理。 Purple organic layer was separated (400ml), then dried over magnesium (15g) and DarcoG60 charcoal (2.2g) processing. 浆料剧烈搅拌40分钟。 Slurry was stirred vigorously for 40 minutes. 浆料过滤以除去硫酸镁和活性炭。 Slurry was filtered to remove the magnesium sulfate and charcoal. 在旋转蒸发仪上浓缩滤液。 The filtrate was concentrated on a rotary evaporator. 产物由深琥珀色油(61.2g，95％收率)组成，在放置后结晶。 The product from deep amber oil (61.2g, 95% yield) composed of the crystallized on standing. 经1HNMR观测到的杂质仅有0.7％的乙腈。 1HNMR impurity observed by only 0.7% acetonitrile.

1H NMR(DMSO-d6)δ1.15(t，3H)，3.29(dd，1H)，3.60(dd，1H)，4.11(q，2H)，5.20(dd，1H)，6.99(dd，1H)，7.84(d，1H)，8.12(d，1H)。 1H NMR (DMSO-d6) δ1.15 (t, 3H), 3.29 (dd, 1H), 3.60 (dd, 1H), 4.11 (q, 2H), 5.20 (dd, 1H), 6.99 (dd, 1H) , 7.84 (d, 1H), 8.12 (d, 1H).

步骤B：3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸乙酯(或者命名为1-(3-氯-2-吡啶基)-3-溴吡唑-5-羧酸乙酯)的制备在装有机械搅拌器、温度计、回流冷凝器和氮气入口的1-L四颈烧瓶中装入3-溴-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯(即步骤A1和A2的产物)(40.2g，0.121mol)，乙腈(300ml)和硫酸(98％，13.0ml，0.245mol)。 Step B: 3- bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylate (or named as 1- (3-chloro-2-pyridinyl) -3- bromo-pyrazole-5-carboxylate) To a solution of 3-bromo charged equipped with a mechanical stirrer, thermometer, reflux condenser and nitrogen inlet 1-L four-necked flask -1- (3-chloro-2 - pyridyl) -4,5-dihydro -1H- pyrazole-5-carboxylate (i.e. the product of Step A1 and A2) (40.2g, 0.121mol), acetonitrile (300ml) and sulfuric acid (98%, 13.0ml, 0.245mol). 一加入硫酸，混合物即自身放热从22℃至36℃。 An addition of sulfuric acid, a mixture that is self-heating from 22 ℃ to 36 ℃. 在搅拌几分钟后，用过硫酸钾(48.0g，0.178mol)处理混合物。 After stirring for a few minutes, the used potassium sulfate (48.0g, 0.178mol) processing the mixture. 浆料加热至在84℃回流2小时。 Slurry was heated to reflux for 2 hours at 84 ℃. 将所得的橙色浆料在仍温(50-65℃)时过滤，以除去白色沉淀。 The resulting orange slurry while still warm (50-65 ℃) filtration to remove a white precipitate. 用乙腈(2×50ml)洗涤滤饼。 (2 × 50ml) The filter cake was washed with acetonitrile. 将滤液在旋转蒸发仪上浓缩至约200ml。 The filtrate was concentrated on a rotary evaporator to about 200ml. 在装有机械搅拌器的另一个1-L四颈瓶中装入水(400ml)。 Equipped with a mechanical stirrer, another 1-L four-necked flask was charged with water (400ml). 在约5分钟的时间内将浓缩的反应物料加入到水中。 In about 5 minutes and the concentrated reaction mass was added to the water. 经过滤分离产物，相继用含水乙腈(20％，100ml)和水(75ml)洗涤，然后在过滤器上风干1小时。 The product was isolated by filtration, washed sequentially with aqueous acetonitrile (20%, 100ml) and water (75ml) and washed, and then air-dried on the filter for 1 hour. 产物由结晶橙色粉末(36.6g，90％收率)组成。 The product crystallized from an orange powder (36.6g, 90% yield) composition. 经1H NMR观测到仅有的杂质为约1％未知物质和0.5％乙腈。 Observed by 1H NMR was only about 1% of unknown impurity material and 0.5% acetonitrile.

1H NMR(DMSO-d6)δ1.09(t，3H)，4.16(q，2H)，7.35(s，1H)，7.72(dd，1H)，8.39(d，1H)，8.59(d，1H)。 1H NMR (DMSO-d6) δ1.09 (t, 3H), 4.16 (q, 2H), 7.35 (s, 1H), 7.72 (dd, 1H), 8.39 (d, 1H), 8.59 (d, 1H) .

步骤C：3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸(或者命名为1-(3-氯-2-吡啶基)-3-溴吡唑-5-羧酸)的制备在装有机械搅拌器、温度计和氮气入口的300-mL四颈烧瓶中装入3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸乙酯(即步骤B的产物)(98.5％纯，25.0g，0.0756mol)，甲醇(75ml)，水(50ml)和氢氧化钠片(3.30g，0.0825mol)。 Step C: 3- bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid (or named as 1- (3-chloro-2-pyridinyl) -3-bromo-pyrazol oxazole-5-carboxylic acid) is prepared equipped with a mechanical stirrer, a thermometer and a nitrogen inlet 300-mL four-necked flask was charged with 3-bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazol oxazole-5-carboxylate (i.e. product of Step B) (98.5% pure, 25.0g, 0.0756mol), methanol (75ml), water (50ml) and sodium hydroxide pellets (3.30g, 0.0825mol). 一加入氢氧化钠，混合物即自身放热从29℃至34℃并且起始物质开始溶解。 A solution of sodium hydroxide, the mixture of starting material that is self-heating and began to dissolve from 29 ℃ to 34 ℃. 在环境条件下搅拌90分钟后，所有的起始物质都已溶解。 Was stirred at ambient conditions for 90 minutes, all the starting material had dissolved. 在旋转蒸发仪上浓缩所得深橙色溶液至约90ml。 On a rotary evaporator and the resulting dark orange solution was concentrated to about 90ml. 然后用水(160ml)稀释浓缩的反应混合物。 Then washed with water (160ml) dilution of the concentrated reaction mixture. 用乙醚(100ml)萃取含水溶液。 With diethyl ether (100ml) and extracted aqueous solution. 然后将水层转移入装有磁力搅拌器的500-ml锥形瓶中。 The aqueous layer was then equipped with a magnetic stirrer, transferred into a 500-ml Erlenmeyer flask. 用浓盐酸(8.50g，0.0839mol)滴加处理溶液约10分钟。 Treated dropwise with concentrated hydrochloric acid (8.50g, 0.0839mol) solution for about 10 minutes. 经过滤分离产物，用水(2×40ml)使其再成为浆料，用水(25ml)覆盖洗涤一次，然后在过滤器上风干2小时。 The product was isolated by filtration, washed with water (2 × 40ml) it was reslurried with water (25ml), washed once covered, and then air-dried on the filter for 2 hours. 产物由晶体状的、棕黄色粉末(20.9g，91％收率)组成。 Product by crystal-shaped, brown-yellow powder (20.9g, 91% yield) components. 经1H NMR观测到的仅有杂质为约0.8％未知物质和0.7％乙醚。 By 1H NMR observed only about 0.8% of impurities and 0.7% ether unknown substance.

1H NMR(DMSO-d6)δ7.25(s，1H)，13.95(br s，1H)，8.56(d，1H)，8.25(d，1H)，7.68(dd，1H)。 1H NMR (DMSO-d6) δ7.25 (s, 1H), 13.95 (br s, 1H), 8.56 (d, 1H), 8.25 (d, 1H), 7.68 (dd, 1H).

下面的实施例14说明3-溴-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯的另一制备，该物质可以用于制备，例如，3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸乙酯(即实施例13，步骤B的产物)。 The following Example 14 illustrates the 3-bromo-1- (3-chloro-2-pyridinyl) -4,5-dihydro -1H- pyrazole-5-carboxylic acid ethyl ester another, the substance can be used in the preparation of, e.g., 3-bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylate (i.e., Example 13, the product of step B).

实施例14使用溴化氢由3-氯-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯制备3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸乙酯将溴化氢通入二溴甲烷(85ml)中的3-溴-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯(即实施例12，步骤B的产物)(8.45g，29.3mmol)溶液中。 Example 14 Use of hydrogen bromide from 3-chloro-1- (3-chloro-2-pyridinyl) -4,5-dihydro -1H- pyrazole-5-carboxylic acid ethyl ester Preparation of 3-bromo-1- embodiment (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylate hydrogen bromide passed into dibromomethane (85ml) of 3-bromo-1- (3-chloro-2-pyridyl ) -4,5-dihydro -1H- pyrazole-5-carboxylate (i.e., Example 12, the product of Step B) (8.45g, 29.3mmol) in solution. 90分钟后，停止通入气体，用碳酸氢钠水溶液(100ml)洗涤反应混合物。 After 90 minutes, the gas was stopped, with aqueous sodium bicarbonate (100ml) was washed with the reaction mixture. 干燥有机相，并在减压下蒸发，得到油状的标题产物(9.7g，99％收率)，该产物在放置后结晶。 The organic phase was dried and evaporated under reduced pressure to give the title product as an oil (9.7g, 99% yield), the product crystallized on standing.

1H NMR(CDCl3)δ1.19(t，3H)，3.24(在ABX模式中的AB的1/2，J＝9.3，17.3Hz，1H)，3.44(在ABX模式中的AB的1/2，J＝11.7，17.3Hz，1H)，4.18(q，2H)，5.25(ABX的X，1H，J＝9.3，11.9Hz)，6.85(dd，J＝4.7，7.7Hz，1H)，7.65(dd，J＝1.6，7.8Hz，1H)，8.07(dd，J＝1.6，4.8Hz，1H)。 1H NMR (CDCl3) δ1.19 (t, 3H), 3.24 (AB in ABX pattern of the 1/2, J = 9.3,17.3Hz, 1H), 3.44 (AB in ABX pattern of 1/2, J = 11.7,17.3Hz, 1H), 4.18 (q, 2H), 5.25 (ABX of X, 1H, J = 9.3,11.9Hz), 6.85 (dd, J = 4.7,7.7Hz, 1H), 7.65 (dd , J = 1.6,7.8Hz, 1H), 8.07 (dd, J = 1.6,4.8Hz, 1H).

下面的实施例15说明1-(3-氯-2-吡啶基)-4，5-二氢-3-[[(4-甲基苯基)磺酰基]氧]-1H-吡唑-5-羧酸乙酯的制备，通过与实施例14中描述的类似方法，该物质可用于制备3-溴-1-(3-氯-2-吡啶基)-4，5-二氢-1H-吡唑-5-羧酸乙酯。 The following Example 15 illustrates the 1- (3-chloro-2-pyridinyl) -4,5-dihydro-3 - [[(4-methylphenyl) sulfonyl] oxy] -1H- pyrazole -5 - carboxylic acid ethyl ester, by the method similar to Example 14 as described, the material used for making 3-bromo-1- (3-chloro-2-pyridinyl) -4,5-dihydro -1H- pyrazole-5-carboxylate.

实施例151-(3-氯-2-吡啶基)-4，5-二氢-3-[[(4-甲基苯基)磺酰基]羟基]-1H-吡唑-5-羧酸乙酯的制备在0℃下，将三乙胺(3.75g，37.1mmol)滴加至在二氯甲烷(100ml)中的2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷羧酸乙酯(即实施例12，步骤A的产物)(10.0g，37.1mmol)和对甲苯磺酰氯(7.07g，37.1mmol)的混合物中。 EXAMPLE 151- (3-chloro-2-pyridinyl) -4,5-dihydro-3 - [[(4-methylphenyl) sulfonyl] hydroxy] -1H- pyrazole-5-carboxylic acid ethyl Preparation of the ester at 0 ℃, triethylamine (3.75g, 37.1mmol) was added dropwise to the dichloromethane (100ml) of 2- (3-chloro-2-pyridinyl) -5-oxo-3 pyrazolidine-carboxylate (i.e., Example 12, the product of Step A) (10.0g, 37.1mmol) and a mixture of p-toluenesulfonyl chloride (7.07g, 37.1mmol) in. 再加入对甲苯磺酰氯(0.35g，1.83mmol)和三乙胺(0.19g，1.88mmol)。 Was added p-toluenesulfonyl chloride (0.35g, 1.83mmol) and triethylamine (0.19g, 1.88mmol). 然后让反应混合物升温至室温并搅拌过夜。 The reaction mixture was then allowed to warm to room temperature and stirred overnight. 用二氯甲烷(200ml)稀释混合物并用水(3×70ml)洗涤。 Diluted with dichloromethane (200ml) and the mixture was washed with water (3 × 70ml) and washed. 干燥有机相并蒸发，以留下油状的标题产物(13.7g，87％收率)，该产物缓慢形成晶体。 The organic phase was dried and evaporated to leave the title product as an oil (13.7g, 87% yield), which was slowly formed crystals. 从乙酸乙酯/己烷重结晶的产物在99.5-100℃熔化。 The product from ethyl acetate / hexane recrystallization melted at 99.5-100 ℃.

IR(nujol)v 1740，1638，1576，1446，1343，1296，1228，1191，1178，1084，1027，948，969，868，845cm-11H NMR(CDCl3)δ1.19(t，3H)，2.45(s，3H)，3.12(在ABX模式中的AB的1/2，J＝17.3，9Hz，1H)，3.33(在ABX模式中的AB的1/2，J＝17.5，11.8Hz，1H)，4.16(q，2H)，5.72(ABX的X，J＝9，11.8Hz，1H)，6.79(dd，J＝4.6，7.7Hz，1H)，7.36(d，J＝8.4Hz，2H)，7.56(dd，J＝1.6，7.8Hz，1H)，7.95(d，J＝8.4Hz，2H)，8.01(dd，J＝1.4，4.6Hz，1H)。 IR (nujol) v 1740,1638,1576,1446,1343,1296,1228,1191,1178,1084,1027,948,969,868,845cm-11H NMR (CDCl3) δ1.19 (t, 3H), 2.45 (s, 3H), 3.12 (ABX mode in the 1/2 AB's, J = 17.3,9Hz, 1H), 3.33 (AB in ABX pattern of the 1/2, J = 17.5,11.8Hz, 1H) , 4.16 (q, 2H), 5.72 (ABX of X, J = 9,11.8Hz, 1H), 6.79 (dd, J = 4.6,7.7Hz, 1H), 7.36 (d, J = 8.4Hz, 2H), 7.56 (dd, J = 1.6,7.8Hz, 1H), 7.95 (d, J = 8.4Hz, 2H), 8.01 (dd, J = 1.4,4.6Hz, 1H).

实施例16N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-酰胺的制备步骤A：1-(3-氯-2-吡啶基)-2，3-二氢-3-氧-1H-吡唑-5-羧酸乙酯的制备将硫酸(20g，200mmol)一次加入到干燥乙腈(200ml)中经搅拌的2-(3-氯-2-吡啶基)-5-氧-3-吡唑烷羧酸乙酯(即实施例12，步骤A的产物)(27g，100mmol)悬浮液中。 Example 16N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -3- (2,2,2- trifluoro-ethoxy) -1H- pyrazole-5-carboxamide Preparation of Step A: 1- (3- chloro-2-pyridyl) -2,3-dihydro-3-oxo -1H- pyrazole -5 - carboxylic acid ethyl ester Sulfuric acid (20g, 200mmol) was added to the dry acetonitrile (200ml) in a stirred solution of 2- (3-chloro-2-pyridinyl) -5-oxo-3-pyrazole-carboxylic acid ethyl ester (i.e., Example 12, the product of Step A) (27g, 100mmol) suspension. 反应混合物变稀形成淡绿色，接近清彻的溶液，然后变稠形成淡黄色悬浮液。 The reaction mixture was thinning formed light green, near clear solution, and then became thick pale yellow suspension was formed. 一次加入过硫酸钾(33g，120mmol)，然后反应混合物加热至温和回流3.5小时。 Was added potassium persulfate (33g, 120mmol), and then the reaction mixture was heated to a gentle reflux for 3.5 hours. 在用冰浴冷却后，过滤除去白色固体沉淀并弃去。 After cooling in an ice-bath, a white solid precipitate was removed by filtration and discarded. 用水(400ml)稀释滤液，然后用乙醚(总计700ml)萃取三次。 Washed with water (400ml) The filtrate was diluted with ether (total 700ml) and extracted three times. 浓缩合并的乙醚萃取物至更少体积(75ml)，使得出现乳白色固体沉淀(3.75g)，过滤收集之。 The combined ether extracts were concentrated to a smaller volume (75ml), so appear milky white solid precipitate (3.75g), collected by filtration. 进一步浓缩乙醚母液产生第二部分乳白色沉淀物(4.2g)，再次过滤收集沉淀。 Ether mother liquor was further concentrated to produce a second portion milky white precipitate (4.2g), again collected by filtration. 乳白色固体也由水相沉淀；过滤收集该固体(4.5g)，合并得到总计为12.45的标题化合物。 Cream solid also precipitated from the aqueous phase; The solid was collected by filtration (4.5g), combined to give the title compound 12.45 totaled.

1H NMR(DMSO-d6)δ1.06(t，3H)，4.11(q，2H)，6.34(s，1H)，7.6(t，1H)，8.19(d，1H)，8.5(d，1H)，10.6(s，1H)。 1H NMR (DMSO-d6) δ1.06 (t, 3H), 4.11 (q, 2H), 6.34 (s, 1H), 7.6 (t, 1H), 8.19 (d, 1H), 8.5 (d, 1H) , 10.6 (s, 1H).

步骤B：1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-羧酸乙酯的制备将碳酸钾(0.85g，6.15mmol)加入到-5℃的干燥乙腈(15ml)中经搅拌的1-(3-氯-2-吡啶基)-2，3-二氢-3-氧-1H-吡唑-5-羧酸乙酯(即步骤A的产物)(0.8g，3mmol)悬浮液中。 Step B: 1- (3- chloro-2-pyridinyl) -3- (2,2,2-trifluoroethoxy) -1H- pyrazole-5-carboxylic acid ethyl ester Potassium carbonate (0.85 g, 6.15mmol) was added to the dry acetonitrile -5 ℃ (15ml) in a stirred solution of 1- (3-chloro-2-pyridinyl) -2,3-dihydro-3-oxo -1H- pyrazole -5 - carboxylate (i.e. product of Step A) (0.8g, 3mmol) suspension. 悬浮液在20℃下搅拌15分钟。 The suspension was stirred at 20 ℃ 15 minutes. 然后将经搅拌的悬浮液冷却至5℃，并滴加2，2，2-三氟乙基三氟甲烷磺酸酯(0.8g，3.45mmol)。 After the suspension was then cooled with stirring to 5 ℃, and a solution of 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.8g, 3.45mmol). 反应混合物升温至室温，然后加热至回流，此时薄层色谱显示反应完全。 The reaction mixture was allowed to warm to room temperature and then heated to reflux at which point thin layer chromatography showed complete reaction. 加水(25ml)至反应混合物，然后用乙醚萃取。 Water was added (25ml) to the reaction mixture, and then extracted with ether. 用硫酸镁干燥乙醚萃取物并浓缩以产生标题产物化合物(1.05g)，为淡黄色油。 The ether extract was dried over magnesium sulfate and concentrated to yield the title product compound (1.05g), as a pale yellow oil.

1H NMR(CDCl3)δ1.21(t，3H)，4.20(q，2H)，4.63(q，2H)，6.53(s，1H)，7.4(t，1H)，7.9(d，1H)，8.5(d，1H)。 1H NMR (CDCl3) δ1.21 (t, 3H), 4.20 (q, 2H), 4.63 (q, 2H), 6.53 (s, 1H), 7.4 (t, 1H), 7.9 (d, 1H), 8.5 (d, 1H).

步骤C：1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-羧酸的制备将水(5ml)加入甲醇(15ml)中的1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-羧酸乙酯(即步骤B的产物)(0.92g，2.8mmol)的经搅拌的溶液中，这使得反应混合物变得混浊。 Step C: 1- (3- chloro-2-pyridinyl) -3- (2,2,2-trifluoroethoxy) -1H- pyrazole 5-carboxylic acid to water (5ml) was added methanol (15ml) of 1- (3-chloro-2-pyridinyl) -3- (2,2,2-trifluoroethoxy) -1H- pyrazole-5-carboxylate (i.e., Step B product) (0.92g, 2.8mmol) To a stirred solution, which makes the reaction mixture became cloudy. 滴加氢氧化钠水溶液(50％，1.5g，19.2mmol)，并且在室温下将反应混合物搅拌30分钟，其间反应混合物又变清亮。 Was added dropwise aqueous sodium hydroxide (50%, 1.5g, 19.2mmol), and the reaction mixture was stirred at room temperature for 30 minutes, during which the reaction mixture becomes clear again. 加入水(20ml)，并用乙醚萃取反应混合物，弃去萃取物。 Water was added (20ml), and the reaction mixture was extracted with diethyl ether, the extract was discarded. 用浓盐酸将水相酸化至pH2，然后用乙酸乙酯(50ml)萃取。 With concentrated hydrochloric acid and the aqueous phase was acidified to pH2, followed by extraction with ethyl acetate (50ml). 用水(20ml)和盐水(20ml)洗涤乙酸乙酯萃取物，用硫酸镁干燥并浓缩，得到标题化合物，分离为白色固体(0.8g)。 Washed with water (20ml) and brine (20ml) washed with ethyl acetate extracts were combined, dried over magnesium sulfate and concentrated to give the title compound, isolated as a white solid (0.8g).

1H NMR(DMSO-d6)δ4.9(q，2H)，6.75(s，1H)，7.6(t，1H)，8.2(d，1H)，8.55(d，1H)，13.7(bs，1H)。 1H NMR (DMSO-d6) δ4.9 (q, 2H), 6.75 (s, 1H), 7.6 (t, 1H), 8.2 (d, 1H), 8.55 (d, 1H), 13.7 (bs, 1H) .

步骤D：6-氯-8-甲基-2H-3，1-苯并噁嗪-2，4(1H)-二酮的制备将氯甲酸三氯甲酯(63g，320mmol)滴加到室温的干燥二噁烷(750ml)中经搅拌的2-氨基-3-甲基-5-氯苯甲酸(即实施例6，步骤A的产物)的悬浮液中。 Step D: 6- chloro-8-methyl -2H-3,1- benzoxazine -2,4 (1H) - dione prepared trichloromethyl chloroformate (63g, 320mmol) was added dropwise at room temperature dry dioxane (750ml) in a stirred solution of 2-amino-3-methyl-5-chlorobenzoic acid (6, i.e. the product of Step A Example) suspension. 反应混合物放热缓慢升温至42℃，固体几乎完全溶解，之后又形成稠的悬浮液。 The reaction mixture exothermed slowly warmed to 42 ℃, the solid almost completely dissolved, and later formed a thick suspension. 将该悬浮液在环境温度下搅拌2.5小时后，过滤分离标题化合物，用乙醚洗涤，并干燥，得到标题化合物，为白色固体(98g)。 The suspension was stirred at ambient temperature for 2.5 hours, the title compound was isolated by filtration, washed with ether, and dried to give the title compound as a white solid (98g).

1H NMR(DMSO-d6)δ2.3(s，3H)，7.70(s，1H)，7.75(s，1H)，11.2(s，1H)。 1H NMR (DMSO-d6) δ2.3 (s, 3H), 7.70 (s, 1H), 7.75 (s, 1H), 11.2 (s, 1H).

步骤E：6-氯-2-[1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-基]-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备将N，N-二甲基甲酰胺(4滴)加入在二氯甲烷(100ml)中经搅拌的1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-羧酸(即步骤C的产物)(7.9g，24mmol)的悬浮液中。 Step E: 6- chloro-2- [1- (3-chloro-2-pyridinyl) -3- (2,2,2-trifluoroethoxy) -1H- pyrazol-5-yl] -8 - preparation of benzoxazin-4-one-methyl -4H-3,1- the N, N- dimethylformamide (4 drops) was added (100ml) stirred in dichloromethane in 1- (3 - chloro-2-pyridinyl) -3- (2,2,2-trifluoroethoxy) -1H- pyrazole-5-carboxylic acid (i.e. product of Step C) (7.9g, 24mmol) suspension in. 在45分钟的时间内滴加草酰氯(4.45g，35mmol)。 Oxalyl chloride was added dropwise over 45 minutes (4.45g, 35mmol). 将所得溶液在室温下搅拌4小时，然后真空浓缩。 The resulting solution was stirred for 4 hours at room temperature and then concentrated in vacuo. 将分离的酰氯溶解在干燥的乙腈(10ml)中，并加入在干燥乙腈(14ml)中经搅拌的6-氯-8-甲基-2H-3，1-苯并噁嗪-2，4(1H)-二酮(即步骤D的产物)(4.9g，23mmol)的悬浮液中。 The isolated acid chloride was dissolved in dry acetonitrile (10ml) and a solution in dry acetonitrile (14ml) in a stirred solution of 6-chloro-8-methyl -2H-3,1- benzoxazine-2,4 ( 1H) - dione (i.e. the product of Step D) (4.9g, 23mmol) suspension. 加入吡啶(10ml)，将溶液加热回流6小时。 Pyridine (10ml), the solution was heated at reflux for 6 hours. 用冰浴冷却后，收集白色固体沉淀(9.15g)。 After ice-cooling, a white solid precipitate was collected (9.15g). 所收集的沉淀的1H NMR谱显示由标题化合物和残留的6-氯-8-甲基-2H-3，1-苯并噁嗪-2，4(1H)-二酮起始物质组成的波峰。 The precipitate was collected by 1H NMR spectra show the title compound and residual 6-chloro-8-methyl -2H-3,1- benzoxazine -2,4 (1H) - dione starting material consisting of peaks . 将收集的沉淀的一小部分从乙腈中重结晶，得到纯的标题产物，该产物在178-180℃熔化。 A small portion of the collected precipitate was recrystallized from acetonitrile to give the pure title product which melted at 178-180 ℃.

1H NMR(DMSO-d6)δ1.72(s，3H)，4.96(q，2H)，7.04(s，1H)，7.7(t，1H)，7.75(s，1H)，7.9(s，1H)，8.3(d，1H)，8.6(d，1H)。 1H NMR (DMSO-d6) δ1.72 (s, 3H), 4.96 (q, 2H), 7.04 (s, 1H), 7.7 (t, 1H), 7.75 (s, 1H), 7.9 (s, 1H) , 8.3 (d, 1H), 8.6 (d, 1H).

步骤F：N-[4-氯-2-甲基-6-[(甲基氨基)羰基]苯基]-1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-酰胺的制备将甲胺(THF中的2.0M溶液，11ml，22mmol)滴加到在四氢呋喃(15ml)中的6-氯-2-[1-(3-氯-2-吡啶基)-3-(2，2，2-三氟乙氧基)-1H-吡唑-5-基]-8-甲基-4H-3，1-苯并噁嗪-4-酮(即步骤E的沉淀产物)(3.53g，7.5mmol)的悬浮液中，并将所得溶液在室温下搅拌45分钟。 Step F: N- [4- chloro-2-methyl-6 - [(methylamino) carbonyl] phenyl] -1- (3-chloro-2-pyridinyl) -3- (2,2,2 - trifluoroethoxy) -1H- pyrazole-5-carboxamido will methylamine (THF solution of 2.0M, 11ml, 22mmol) was added dropwise to tetrahydrofuran (15ml) in 6-chloro-2- [ 1- (3-chloro-2-pyridinyl) -3- (2,2,2-trifluoroethoxy) -1H- pyrazol-5-yl] -8-methyl -4H-3,1- benzoxazin-4-one (i.e. precipitate product of Step E) (3.53g, 7.5mmol) suspension, and the resulting solution was stirred at room temperature for 45 minutes. 然后薄层色谱表明反应完全。 And thin layer chromatography showed complete reaction. 加入乙醚(100ml)，将反应混合物搅拌2小时，同时形成沉淀。 Was added diethyl ether (100ml), and the reaction mixture was stirred for 2 hours while a precipitate formed. 过滤收集沉淀，然后由乙腈重结晶，得到白色固体(0.82g)。 The precipitate was collected by filtration, and then recrystallized from acetonitrile to give a white solid (0.82g). 由乙腈母液沉淀第二批白色固体(0.35g)，并经过滤收集之。 The second batch precipitated from the acetonitrile mother liquor white solid (0.35g), and collected by filtration. 将最初的乙醚/四氢呋喃母液浓缩至干，残留固体由乙腈重结晶，得到第三批白色固体(0.95g)。 The initial ether / tetrahydrofuran mother liquor was concentrated to dryness, the residual solid was recrystallized from acetonitrile to give a third batch of white solid (0.95g). 合并三批产物，总计2.12g(干燥后)的标题化合物，本发明的化合物，分离为白色固体，在195-197℃熔化。 The combined product batches, total 2.12g (after drying) of the title compound, compounds of the invention, isolated as a white solid, melting at 195-197 ℃.

1H NMR(CDCl3)δ2.18(s，3H)，2.92(d，3H)，4.66(q，2H)，6.15(q，1H)，6.6(s，1H)，7.2(s，1H)，7.25(s，1H)，7.35(t，1H)，7.8(d，1H)，8.45(d，1H)，10.0(s，1H)。 1H NMR (CDCl3) δ2.18 (s, 3H), 2.92 (d, 3H), 4.66 (q, 2H), 6.15 (q, 1H), 6.6 (s, 1H), 7.2 (s, 1H), 7.25 (s, 1H), 7.35 (t, 1H), 7.8 (d, 1H), 8.45 (d, 1H), 10.0 (s, 1H).

下面的实施例17说明1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的另一制备，通过实施例4中所述的进一步的步骤，该物质可用于制备，例如，1-(3-氯-2-吡啶基)-N-[2-甲基-6-[[(1-甲基乙基)氨基]羰基]苯基]-3-(三氟甲基)-1H-吡唑-5-酰胺。 The following Example 17 illustrates 1- (3-chloro-2-pyridinyl) -3- another preparation of (trifluoromethyl) -1H- pyrazole-5-carboxylic acid, as described by Example 4 further step, the substance can be used to prepare, for example, 1- (3-chloro-2-pyridinyl) -N- [2- methyl-6 - [[(1-methylethyl) amino] carbonyl] benzene yl] -3- (trifluoromethyl) -1H- pyrazole-5-carboxamide.

实施例171-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备步骤A：3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亚乙基)腙的制备在20-25℃下，将1，1，1-三氟丙酮(7.80g，69.6mmol)加入3-氯-2(1H)-吡啶酮腙(或者命名为(3-氯-吡啶-2基)-腙)(10g，69.7mmol)中。 EXAMPLE 171- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxylic acid Step A: 3- chloro -2 (1H) - pyridone ( 2,2,2-trifluoro-1-methylethylidene) hydrazone at 20-25 ℃, 1,1,1-trifluoro-acetone (7.80g, 69.6mmol) was added 3-chloro-2 (1H) - pyridinone hydrazone (or named (3-chloro - pyridin-2-yl) - hydrazone) (10g, 69.7mmol) in. 加入完成后，将混合物搅拌约10分钟。 After addition was complete, the mixture was stirred for about 10 minutes. 减压除去溶剂，使混合物在乙酸乙酯(100ml)和饱和碳酸钠水溶液(100ml)间分配。 The solvent was removed under reduced pressure, the mixture was partitioned between ethyl acetate (100ml) and saturated aqueous sodium carbonate solution (100ml) between. 干燥有机层并蒸发。 The organic layer was dried and evaporated. 硅胶层析(用乙酸乙酯洗脱)给出乳白色固体产物(11g，66％收率)，mp64-64.5℃(在从乙酸乙酯/己烷结晶后)。 Chromatography on silica gel (elution with ethyl acetate) to give a cream colored solid product (11g, 66% yield), mp64-64.5 ℃ (after from ethyl acetate / hexane to).

IR(nujol)v 1629，1590，1518，1403，1365，1309，1240，1196，1158，1100，1032，992，800cm-11H NMR(CDCl3)δ2.12(s，3H)，6.91-6.86(m，1H)，7.64-7.61(m，1H)，8.33-8.32(m，2H)。 IR (nujol) v 1629,1590,1518,1403,1365,1309,1240,1196,1158,1100,1032,992,800cm-11H NMR (CDCl3) δ2.12 (s, 3H), 6.91-6.86 (m , 1H), 7.64-7.61 (m, 1H), 8.33-8.32 (m, 2H).

MS m/z 237(M+)步骤B：乙基氢乙二酯(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亚乙基基)腙(或者命名为乙基氢乙二酯(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亚乙基基)腙)的制备在0℃下，将三乙胺(20.81g，0.206mmol)加入在二氯甲烷(68ml)中的3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亚乙基)腙(即步骤A的产物)(32.63g，0.137mol)中。 MS m / z 237 (M +) Step B: Ethyl hydrogen terephthalate (3-chloro-2-pyridinyl) (2,2,2-trifluoro-methylsulfinyl ethyl groups) hydrazone (or named hydrogen terephthalate is ethyl (3-chloro-2-pyridinyl) (2,2,2-trifluoro-methylsulfinyl ethyl groups) hydrazone) is prepared at 0 ℃, triethylamine ( 20.81g, 0.206mmol) was added dichloromethane (68ml) in a 3-chloro -2 (1H) - pyridone (2,2,2-trifluoro-1-methylethylidene) hydrazone (i.e., Step A product) (32.63g, 0.137mol) in. 在0℃下，将在二氯甲烷(69ml)中的氯氧乙酸乙酯(18.75g，0.137mol)滴加到该混合物中。 At 0 ℃, dichloromethane (69ml) in ethyl oxychloride (18.75g, 0.137mol) was added dropwise to the mixture. 使该混合物在约2小时内升温至25℃。 The mixture was heated over about 2 hours to 25 ℃. 使该混合物冷却至0℃并进一步滴加在二氯甲烷(14ml)中的氯氧乙酸乙酯(3.75g，27.47mmol)。 The mixture was cooled to 0 ℃ and further added dropwise in dichloromethane (14ml) in ethyl oxychloride (3.75g, 27.47mmol). 再过约1小时后，用二氯甲烷(约450ml)稀释该混合物，用水(2×150ml)洗涤该混合物。 Another about 1 hour, the mixture was diluted with dichloromethane (about 450ml), washed with water (2 × 150ml) and the mixture was washed. 干燥有机层并蒸发。 The organic layer was dried and evaporated. 硅胶层析(用1∶1乙酸乙酯-己烷洗脱)给出固体产物(42.06g，90％收率)，mp73.0-73.5℃(从乙酸乙酯/己烷结晶后)。 Silica gel chromatography (ethyl acetate with 1:1 - hexane) to give the solid product (42.06g, 90% yield), mp73.0-73.5 ℃ (after from ethyl acetate / hexane to).

IR(nujol)v 1751，1720，1664，1572，1417，1361，1330，1202，1214，1184，1137，1110，1004，1043，1013，942，807，836cm-11H NMR(DMSO-d6，115℃)1.19(t，3H)，1.72(br s，3H)，4.25(q，2H)，7.65(dd，J＝8.3，4.7Hz，1H)，8.20(dd，J＝7.6，1.5Hz，1H)，8.55(d，J＝3.6Hz，1H)。 IR (nujol) v 1751,1720,1664,1572,1417,1361,1330,1202,1214,1184,1137,1110,1004,1043,1013,942,807,836cm-11H NMR (DMSO-d6,115 ℃ ) 1.19 (t, 3H), 1.72 (br s, 3H), 4.25 (q, 2H), 7.65 (dd, J = 8.3,4.7Hz, 1H), 8.20 (dd, J = 7.6,1.5Hz, 1H) , 8.55 (d, J = 3.6Hz, 1H).

步骤C：1-(3-氯-2-吡啶基)-4，5-二氢-5-羟基-3-(三氟甲基)-1H-吡唑-5-羧酸乙酯的制备在8小时内将在二甲基亚砜(25ml)中的乙基氢乙二酯(3-氯-2-吡啶基)(2，2，2-三氟-1-甲基亚乙基)腙(即步骤B的产物)(5g，14.8mmol)加入在二甲亚砜(25ml)中的氟化四丁基铵水合物(10g)中。 Step C: 1- (3- chloro-2-pyridinyl) -4,5-dihydro-5-hydroxy-3- (trifluoromethyl) -1H- pyrazole-5-carboxylic acid ethyl ester in within 8 hours Ethyl hydrogen terephthalate (3-chloro-2-pyridinyl) (2,2,2-trifluoro-1-methylethylidene) hydrazone dimethyl sulfoxide (25ml) at room (i.e. product of Step B) (5g, 14.8mmol) was added dimethylsulfoxide (25ml) in the tetrabutylammonium fluoride hydrate (10g) in. 当加入完成时，将混合物倒入醋酸(3.25g)水溶液(25ml)中。 When the addition was complete, the mixture was poured into acetic acid (3.25g) water (25ml) in. 在25℃下搅拌过夜后，用甲苯(4×25ml)萃取该混合物，并用水(50ml)洗涤合并的甲苯萃取物，干燥并蒸发，得到固体。 After stirring overnight at 25 ℃ with toluene (4 × 25ml) the mixture was extracted, and the toluene extracts were washed with water (50ml) washed, dried and evaporated to give a solid. 硅胶层析(用1∶2的乙酸乙酯-己烷洗涤)给出固体产物(2.91g，50％收率，含有约5％的3-氯-2(1H)-吡啶酮(2，2，2-三氟-1-甲基亚乙基)腙)，mp78-78.5℃(从乙酸乙酯/己烷结晶后)。 Silica gel chromatography (ethyl acetate with 1:2 - hexane washed) to give solid product (2.91g, 50% yield, containing about 5% of 3-chloro -2 (1H) - pyridone (2,2 , 2-trifluoro-1-methylethylidene) hydrazone), mp78-78.5 ℃ (after from ethyl acetate / hexane to).

IR(nujol)v 3403，1726，1618，1582，1407，1320，1293，1260，1217，1187，1150，1122，1100，1067，1013，873，829cm-11H NMR(CDCl3)δ1.19(s，3H)，3.20(ABZ模式的1/2，J＝18Hz，1H)，3.42(ABZ模式的1/2，J＝18Hz，1H)，4.24(q，2H)，6.94(dd，J＝7.9，4.9Hz，1H)，7.74(dd，J＝7.7，1.5Hz，1H)，8.03(dd，J＝4.7，1.5Hz，1H)。 IR (nujol) v 3403,1726,1618,1582,1407,1320,1293,1260,1217,1187,1150,1122,1100,1067,1013,873,829cm-11H NMR (CDCl3) δ1.19 (s, 3H), 3.20 (ABZ pattern 1/2, J = 18Hz, 1H), 3.42 (ABZ pattern 1/2, J = 18Hz, 1H), 4.24 (q, 2H), 6.94 (dd, J = 7.9, 4.9Hz, 1H), 7.74 (dd, J = 7.7,1.5Hz, 1H), 8.03 (dd, J = 4.7,1.5Hz, 1H).

MS m/z 319(M+)步骤D：1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸乙酯的制备将硫酸(浓，2滴)加入在醋酸(10ml)中的1-(3-氯-2-吡啶基)-4，5-二氢-5-羟基-3-(三氟甲基)-1H-吡唑-5-羧酸乙酯(即步骤C的产物)(1g，2.96mmol)中，并使混合物升温至65℃约1小时。 MS m / z 319 (M +) Step D: Preparation of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxylate Sulfuric acid (conc. , 2 drops) was added in acetic acid (10ml) of 1- (3-chloro-2-pyridinyl) -4,5-dihydro-5-hydroxy-3- (trifluoromethyl) -1H- pyrazol - 5- carboxylate (i.e. product of Step C) (1g, 2.96mmol), and the mixture was heated to 65 ℃ about 1 hour. 让混合物冷却至25℃，并在减压下除去大部分醋酸。 The mixture was cooled to 25 ℃, and most of the acetic acid was removed under reduced pressure. 使混合物在饱和碳酸钠水溶液(100ml)和乙酸乙酯(100ml)间分配。 The mixture was partitioned between saturated aqueous sodium carbonate (100ml) and ethyl acetate (100ml) between. 用乙酸乙酯(100ml)进一步萃取水层。 With ethyl acetate (100ml) and the aqueous layer was further extracted. 干燥合并的有机萃取层并浓缩，得到油状产物(0.66g，77％收率)。 The combined organic extracted layer was dried and concentrated to give an oily product (0.66g, 77% yield).

IR(neat)v 3147，2986，1734，1577，1547，1466，1420，1367，1277，1236，1135，1082，1031，973，842，802cm-11H NMR(CDCl3)δ1.23(t，3H)，4.25(q，2H)，7.21(s，1H)，7.48(dd，J＝8.1，4.7Hz，1H)，7.94(dd，J＝6.6，2Hz，1H)，8.53(dd，J＝4.7，1.5Hz，1H)。 IR (neat) v 3147,2986,1734,1577,1547,1466,1420,1367,1277,1236,1135,1082,1031,973,842,802cm-11H NMR (CDCl3) δ1.23 (t, 3H) , 4.25 (q, 2H), 7.21 (s, 1H), 7.48 (dd, J = 8.1,4.7Hz, 1H), 7.94 (dd, J = 6.6,2Hz, 1H), 8.53 (dd, J = 4.7, 1.5Hz, 1H).

MS m/z 319(M+)步骤E：1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸的制备将氢氧化钾(0.5g，85％，2.28mmol)水溶液(1ml)加入在乙醇(3ml)中的1-(3-氯-2-吡啶基)-3-(三氟甲基)-1H-吡唑-5-羧酸乙酯(即步骤D的产物)(0.66g，2.07mmol)中。 MS m / z 319 (M +) Step E: Preparation of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxylic acid Potassium hydroxide (0.5 g, 85%, 2.28mmol) aqueous solution (1ml) was added in ethanol (3ml) of 1- (3-chloro-2-pyridinyl) -3- (trifluoromethyl) -1H- pyrazole-5-carboxylic acid ethyl ester (i.e. the product of Step D) (0.66g, 2.07mmol) in. 约30分钟后，减压除去溶剂，并将混合物溶解在水(40ml)中。 After about 30 minutes, the solvent was removed under reduced pressure, and the mixture was dissolved in water (40ml) in. 用乙酸乙酯(20ml)洗涤溶液。 (20ml) solution was washed with ethyl acetate. 用浓盐酸酸化水层并用乙酸乙酯(3×20ml)萃取。 The aqueous layer was acidified with concentrated hydrochloric acid and extracted with ethyl acetate (3 × 20ml) and used. 干燥合并的萃取物并蒸发，得到固体产物(0.53g，93％收率)，mp178-179℃(从己烷-乙酸乙酯结晶后)。 The combined extracts were dried and evaporated to give a solid product (0.53g, 93% yield), mp178-179 ℃ (from hexane - ethyl acetate after crystallization).

IR(nujol)v 1711，1586，1565，1550，1440，1425，1292，1247，1219，1170，1135，1087，1059，1031，972，843，816cm-11H NMR(DMSO-d6)δ7.61(s，1H)，7.77(m，1H)，8.30(d，1H)，8.60(s，1H)。 IR (nujol) v 1711,1586,1565,1550,1440,1425,1292,1247,1219,1170,1135,1087,1059,1031,972,843,816cm-11H NMR (DMSO-d6) δ7.61 ( s, 1H), 7.77 (m, 1H), 8.30 (d, 1H), 8.60 (s, 1H).

实施例18和19说明在实施例10，步骤E和实施例8，步骤E中分别描述的反应条件的备选方案。 Examples 18 and 19 illustrate alternatives in 10, Step E and Example 8, Step E, respectively, the reaction conditions described embodiments.

实施例182-[3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-基]-6-氯-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备将甲磺酰氯(1.0ml，1.5g，13mmol)溶解在乙腈(10ml)中，并将该混合物冷却至-5℃。 Example 182- [3-bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazol-5-yl] -6-chloro-8-methyl -4H-3,1- benzoxazin Preparation-4-one Methanesulfonyl chloride (1.0ml, 1.5g, 13mmol) was dissolved in acetonitrile (10ml), and the mixture was cooled to -5 ℃. 在-5至0℃下，在5分钟内滴加在乙腈(10ml)中的3-溴-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸(即实施例10，步骤D的吡唑羧酸产物)(3.02g，10mmol)和吡啶(1.4ml，1.4g，17mmol)溶液中。 At -5 to 0 ℃, was added dropwise over 5 minutes in acetonitrile (10ml) of 3-bromo-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid (i.e., embodiment Example 10, pyrazole carboxylic acid product of Step D) (3.02g, 10mmol) and pyridine (1.4ml, 1.4g, 17mmol) in solution. 在滴加期间形成浆料。 During the dropwise addition to form a slurry. 将混合物在同样的温度下搅拌5分钟，然后加入在乙腈(10ml)中2-氨基-3-甲基-5-氯苯甲酸(即实施例6步骤A的产物)(1.86g，10mmol)和吡啶(2.8ml，2.7g，35mmol)的混合物，用更多的乙腈(5ml)淋洗。 The mixture was stirred for 5 minutes at the same temperature, and then added in acetonitrile (10ml) of 2-amino-3-methyl-5-chlorobenzoic acid (i.e. the product of Example 6 Step A) (1.86g, 10mmol) and pyridine (2.8ml, 2.7g, 35mmol), and with more acetonitrile (5ml) rinse. 将混合物在-5至0℃下搅拌15分钟，然后在-5至0℃下在5分钟内滴加在乙腈(5ml)中的甲磺酰氯(1.0ml，1.5ml，13mmol)溶液。 The mixture was stirred for 15 minutes at -5 to 0 ℃, then at -5 to 0 ℃ added dropwise over 5 minutes in acetonitrile (5ml) of methanesulfonyl chloride (1.0ml, 1.5ml, 13mmol) was added. 在该温度下将反应混合物再搅拌15分钟，然后让其缓慢升温至室温，并搅拌4小时。 The reaction mixture was stirred for 15 minutes at this temperature, then allowed to warm slowly to room temperature and stirred for 4 hours. 滴加水(20ml)，并将该混合物搅拌15分钟。 Dropwise addition of water (20ml), and the mixture was stirred for 15 minutes. 然后过滤该混合物，用2∶1乙腈-水(3×3ml)洗涤固体，然后用乙腈(2×3ml)洗涤，在氮气下干燥，得到标题产物，为淡黄色粉末，4.07g(90.2％粗收率)，在203-205℃熔化。 The mixture was then filtered, with 2:1 acetonitrile - water (3 × 3ml) was washed solid was then washed with acetonitrile (2 × 3ml) was washed, dried under nitrogen to give the title product as a pale yellow powder, 4.07g (90.2% crude yield), melting at 203-205 ℃. 使用ZorbaxRX-C8色谱柱(4.6mm×25cm，洗脱剂25-95％乙腈/pH3水)，产物的HPLC显示相应于标题化合物的主峰，并占总色谱峰面积的95.7％。 Use ZorbaxRX-C8 column (4.6mm × 25cm, eluent 25-95% acetonitrile / pH3 water), HPLC of the product showed a peak corresponding to the title compound and 95.7% of total chromatogram peak area.

1H NMR(DMSO-d6)δ1.72(s，3H)，7.52(s，1H)，7.72-7.78(m，2H)，7.88(m，1H)，8.37(dd，1H)，8.62(dd，1H)。 1H NMR (DMSO-d6) δ1.72 (s, 3H), 7.52 (s, 1H), 7.72-7.78 (m, 2H), 7.88 (m, 1H), 8.37 (dd, 1H), 8.62 (dd, 1H).

实施例196-氯-2-[3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-基]-8-甲基-4H-3，1-苯并噁嗪-4-酮的制备将甲磺酰氯(1.0ml，1.5g，13mmol)溶解在乙腈(10ml)中，并将混合物冷却至-5℃。 Example 196- chloro-2- [3-chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazol-5-yl] -8-methyl -4H-3,1- benzoxazin Preparation-4-one Methanesulfonyl chloride (1.0ml, 1.5g, 13mmol) was dissolved in acetonitrile (10ml), and the mixture was cooled to -5 ℃. 在-5至0℃下，在5分钟内滴加在乙腈(10ml)中的3-氯-1-(3-氯-2-吡啶基)-1H-吡唑-5-羧酸(即实施例8，步骤D的羧酸产物)(2.58g，10mmol)和吡啶(1.4ml，1.4g，17mmol)溶液中。 At -5 to 0 ℃, was added dropwise over 5 minutes in acetonitrile (10ml) of 3-chloro-1- (3-chloro-2-pyridinyl) -1H- pyrazole-5-carboxylic acid (i.e., embodiment Example 8, the carboxylic acid product of Step D) (2.58g, 10mmol) and pyridine (1.4ml, 1.4g, 17mmol) in solution. 在滴加期间形成浆料。 During the dropwise addition to form a slurry. 将该混合物在该温度下搅拌5分钟，然后一次加入所有的2-氨基-3-甲基-5-氯苯甲酸(即实施例6，步骤A的产物)(1.86g，10mmol)。 The mixture was stirred at this temperature for 5 minutes, then was added in all the 2-amino-3-methyl-5-chlorobenzoic acid (i.e., Example 6, the product of Step A) (1.86g, 10mmol). 然后在-5至0℃下，在5分钟内滴加在乙腈(10ml)中的吡啶(2.8ml，2.7g，35mmol)溶液。 Then at -5 to 0 ℃, was added dropwise over 5 minutes in acetonitrile (10ml) in pyridine (2.8ml, 2.7g, 35mmol) was added. 将混合物在-5至0℃下搅拌15分钟，然后在-5至0℃下，在5分中内滴加在乙腈(5ml)中的甲磺酰氯(1.0ml，1.5ml，13mmol)溶液。 The mixture was stirred for 15 minutes at -5 to 0 ℃, then at -5 to 0 ℃, was added dropwise over 5 minutes in acetonitrile (5ml) of methanesulfonyl chloride (1.0ml, 1.5ml, 13mmol) was added. 将反应混合物在该温度下搅拌15分钟，然后让其缓慢升温至室温，并搅拌4小时。 The reaction mixture was stirred for 15 minutes at this temperature, then allowed to warm slowly to room temperature and stirred for 4 hours. 滴加水(15ml)，并将混合物搅拌15分钟。 Dropwise addition of water (15ml), and the mixture was stirred for 15 minutes. 然后过滤混合物，并用2∶1乙腈-水(3×3ml)洗涤固体，然后用乙腈(2×3ml)洗涤，在氮气下干燥，得到标题产物，为淡黄色粉末，3.83g(94.2％粗收率)，在199-201℃熔化。 The mixture was then filtered and dried 2:1 acetonitrile - water (3 × 3ml) was washed solid was then washed with acetonitrile (2 × 3ml) was washed, dried under nitrogen to give the title product as a pale yellow powder, 3.83g (94.2% crude yield rate), melting at 199-201 ℃. 使用ZobaxRX-C8色谱柱(4.6mm×25cm，洗脱剂25-95％乙腈/pH3水)，产物的HPLC显示相应于标题化合物的主峰，并占总色谱峰面积的97.8％。 Use ZobaxRX-C8 column (4.6mm × 25cm, eluent 25-95% acetonitrile / pH3 water), HPLC of the product showed a peak corresponding to the title compound and 97.8% of total chromatogram peak area.

1H NMR(DMSO-d6)δ1.72(s，3H)，7.48(s，1H)，7.74-7.80(m，2H)，7.87(m，1H)，8.37(dd，1H)，8.62(dd，1H)。 1H NMR (DMSO-d6) δ1.72 (s, 3H), 7.48 (s, 1H), 7.74-7.80 (m, 2H), 7.87 (m, 1H), 8.37 (dd, 1H), 8.62 (dd, 1H).

通过本文描述的方法，以及本领域已知的方法，可以制备以下表1-6的化合物。 By the methods described herein, as well as methods known in the art, a compound of the following Table 1-6 can be prepared. 在表中采用的缩写如下：t表示叔，s表示仲，n表示正，i表示异，Me表示甲基，Et表示乙基，Pr表示丙基，i-Pr表示异丙基，而Bu表示丁基。 Abbreviations used in the table as follows: t represents tertiary, s means secondary, n represents normal, i means iso, Me represents methyl, Et represents ethyl, Pr represents propyl group, i-Pr represents an isopropyl group, and Bu represents butyl.

表1 Table 1

表2 Table 2

表3 Table 3

表4 Table 4 <tables id="table16" num="016"> <table width="770">R4R6R3R9aR9bR9cR4R6R3R9aR9bR9cMeMeMeMeClClClClCF3CF3CF3CF3CF3CF3CF3CF3i-Pri-Pri-Pri-Pri-Pri-Pri-Pri-PrMeMeClClMeMeClClHMeHMeHMeHMeMeMeMeMeMeMeMeMeMeMeMeMeClClClClCF3CF3CF3CF3CF3CF3CF3CF3t-But-But-But-But-But-But-But-BuMeMeClClMeMeClClHMeHMeHMeHMeMeMeMeMeMeMeMeMe</table> </tables>表5 <Tables id = "table16" num = "016"> ​​<table width = "770"> R4R6R3R9aR9bR9cR4R6R3R9aR9bR9cMeMeMeMeClClClClCF3CF3CF3CF3CF3CF3CF3CF3i-Pri-Pri-Pri-Pri-Pri-Pri-Pri-PrMeMeClClMeMeClClHMeHMeHMeHMeMeMeMeMeMeMeMeMeMeMeMeMeClClClClCF3CF3CF3CF3CF3CF3CF3CF3t-But-But-But-But-But-But -But-BuMeMeClClMeMeClClHMeHMeHMeHMeMeMeMeMeMeMeMeMe </ table> </ tables> Table 5 <tables id="table17" num="017"> <table width="786">R4R5R6R3R9R4R5R6R3R9CH3CH3CH3CH3CH3FFFFFCF3CF3CF3CF3CF3MeEti-Prt-BuMeClClClClBrClClClClClBrBrBrBrBrClClClClBrMeEti-Prt-BuMeBrBrBrBrCl</table> </tables> <Tables id = "table17" num = "017"> <table width = "786"> R4R5R6R3R9R4R5R6R3R9CH3CH3CH3CH3CH3FFFFFCF3CF3CF3CF3CF3MeEti-Prt-BuMeClClClClBrClClClClClBrBrBrBrBrClClClClBrMeEti-Prt-BuMeBrBrBrBrCl </ table> </ tables>

表6 Table 6

配方/效用已发现式I的化合物不仅具有防治植食性无脊椎害虫的极好活性，而且具有有利的残留模式和植物转移，以提供对由植物繁殖体，如种子、鳞茎、根茎、块茎、球茎，或者茎插或叶插发育而来的植物的保护。 Recipe / utility has found that the compounds of formula I not only herbivorous invertebrate pest prevention excellent activity, but also has a favorable residual patterns and plants are transferred in order to provide the plant propagules, such as seeds, bulbs, rhizomes, tubers, corms or stem or leaf cutting insert developed from the protection of plants. (在本发明公开的上下文中，“无脊椎害虫防治”指抑制无脊椎害虫发育(包括致死性)，所述抑制导致摄食或由害虫引起的其它损伤或伤害显著减少；相关的表述定义类似。)因此，本发明提供通过使植物繁殖体或该繁殖体的场所与生物有效量的式I的化合物接触而保护该繁殖体免受无脊椎害虫侵害的方法。 (In the context of the present disclosure, the term "invertebrate pest control" means inhibition of invertebrate pest development (including lethality), resulted in a significant reduction in the inhibition of feeding or other injury or damage caused by the pest; related expressions similar definition. ) Thus, the present invention provides a compound by contacting plant propagules or the propagules place with a biologically effective amount of formula I protect the propagules from invertebrate pests approach. 还发现使用足量的式I的化合物的本发明的方法不仅保护繁殖体自身，而且也保护从该繁殖体发育而来的新生长。 Also found that the use of a sufficient amount of a compound of formula I of the present invention is not only to protect the body's own breed, but also protect the new growth comes from the development of propagules.

如本文中所述，“处理(treating)”繁殖体或繁殖体的场所指将式I的化合物或含有该化合物的组合物施用于该繁殖体或该繁殖体的场所，使得式I的化合物与该繁殖体接触；相关的术语如“处理(treatment)”定义类似。 As described herein, "treatment (treating)" place propagules or propagules refers to a compound of formula I or a composition containing the compound to the locus of the propagule or the propagules, such that the compound of formula I with The reproduction of body contact; related terms such as "treatment (treatment)" similar definition. 当这样将繁殖体与生物有效量的式I的化合物接触时，该化合物保护其免受植食性无脊椎害虫的侵害。 When such compounds will contact propagules and biologically effective amount of formula I, the compound to protect it from phytophagous invertebrate pests. 式I的化合物不仅保护繁殖体的外表面，而且其将被该繁殖体吸收，产生包含式I的化合物的繁殖体。 Compounds of formula I not only protects the outer surface of the propagule, but it will be the absorption of propagules, generating propagule containing compounds of formula I. 如果该繁殖体与足量的式I的化合物接触，足量的该化合物将被吸收，以在该繁殖体内部产生生物有效量的式I的化合物浓度，因此产生包含生物有效量的式I的化合物的繁殖体。 If the propagule contacted with a sufficient amount of a compound of formula I, a sufficient amount of the compound will be absorbed to produce a biologically effective concentration of the compound of formula I in the amount of the propagation inside, thus creating comprising a biologically effective amount of a Formula I propagules compounds. 如果施用足量的式I的化合物以将该繁殖体中式I的化合物的浓度提高至高于生物有效性所需的最低值，那么将转移生物有效浓度的式I的化合物至发育中的芽和根，以使它们也得到保护。 If the compound is administered a sufficient amount of a compound of formula I at a concentration of compound of formula I in the propagule raised to a value higher than the minimum required for biological effectiveness, then the transfer of the biologically effective concentration of Formula I to the developing shoot and root , so that they are protected.

如本公开中所称，术语“无脊椎害虫”包括作为害虫具有经济重要性的节肢类、腹足类和线虫类。 As referred to in this disclosure, the term "invertebrate pest" includes as an economically important pest arthropods, gastropods and nematodes. 术语“植食性无脊椎害虫”指通过在植物上摄食，如通过食用叶(foliage)、茎、叶(leaf)、果实或种子组织，或者通过吸取植物维管汁液而导致其损伤的无脊椎害虫。 The term "phytophagous invertebrate pest" means by feeding on the plant, such as by eating the leaves (foliage), stems and leaves (leaf), fruit or seed tissue or vascular plants by sucking sap caused the injury of invertebrate pests . 术语“节肢类”包括昆虫、螨、蜈蚣、百足虫、鼠妇和综合纲(symphylans)。 The term "arthropod" includes insects, mites, centipedes, centipedes, rats women and integrated Gang (symphylans). 术语“腹足类”包括蜗牛、蛞蝓和其它有柱腹足目。 The term "gastropod" includes snails, slugs and other pillared Mesogastropoda. 术语“线虫类”包括植食性线虫(线虫门或纲)。 The term "nematode" includes phytophagous nematodes (nematode door or classes). 经济上重要的植食性无脊椎害虫包括：鳞翅目幼虫，如夜蛾科的栗蚕蛾幼虫、切根虫、尺蠖和heliothines(例如草地粘虫(Spodoptera fugiperda JESmith)、甜菜夜蛾(Spodoptera exigua Hübner)、小地蚕(Agrotis ipsilon Hufnagel)、粉纹夜蛾(Trichoplusia ni Hübner)、菸夜蛾(Heliothis virescens Fabricius))；螟蛾科的蛀虫、鞘蛾、结网毛虫、conewoms、cabbageworms(例如玉米螟(Ostrinia nubilalis Hübne)、脐橙螟(Amyelois transitella Walker)、玉米根草螟(Crambus caliginosellus Clemens)、苍螟(Herpetogrammalicarsisalis Walker))；卷蛾科的卷叶虫、卷叶蛾、seed worms和fruitworms(例如苹果蠹蛾(Cydia pomonella L.(L指Linnaeus))、葡萄小食心虫(Endopiza viteana Clemens)、梨小食心虫(Grapholita molestaBusck))；以及许多其它经济上重要的鳞翅目(例如菜蛾(Plutellaxylostella L.)、棉红铃虫(Pectinophore gossypiella Saunders)、舞毒蛾(Lymantria dispar L.))。 Economically important phytophagous invertebrate pests include: Lepidoptera larvae, such as chestnut Noctuidae moth larvae, cutworms, looper and heliothines (eg lawn armyworm (Spodoptera fugiperda JESmith), beet armyworm (Spodoptera exigua Hübner ), small cutworms (Agrotis ipsilon Hufnagel), cabbage looper (Trichoplusia ni Hübner), tobacco budworm (Heliothis virescens Fabricius)); borers Pyralidae, the sheath moth caterpillar webs, conewoms, cabbageworms (such as corn borer (Ostrinia nubilalis Hübne), Orange borer (Amyelois transitella Walker), blades of grass, corn borer (Crambus caliginosellus Clemens), Cang borer (Herpetogrammalicarsisalis Walker)); Tortricidae of leaf insects, leaf rollers, seed worms and fruitworms (such as Apple codling moth (Cydia pomonella L. (L refers Linnaeus)), grape borer (Endopiza viteana Clemens), pear moth (Grapholita molestaBusck)); as well as many other important economic Lepidoptera (eg moth (Plutellaxylostella L. ), pink bollworm (Pectinophore gossypiella Saunders), gypsy moth (Lymantria dispar L.)). 鞘翅目的摄叶幼虫和成虫，包括长角象虫科、豆象科和象虫科的象鼻虫(例如棉铃象鼻虫(Anthonomus grandisBoheman)、稻水象虫(Lissorhoptrus oryzophilus Kuschel)、米象鼻虫(Sitophilus oryzae L.))；叶甲科的跳甲、黄守瓜、食虫、叶甲、薯虫和潜叶虫(例如马铃薯甲虫(Leptinotarsa decemlineata Say)、玉米根叶甲(Diabrotica virgifera LeConte))；金龟子和scaribaeidae的其它甲虫(例如日本丽金龟(Popillia japonica Newman)和欧金龟(Rhizotrogusmajalis Razoumowsky))；叩头甲科的金针虫和棘胫小蠹科的小蠹；革翅目的成虫和幼虫，包括球螋科的蠼螋(例如欧洲蠼螋(Forficulaauricularia L.)、black earwig(Chelisoches morio Fabricius))；半翅目和同翅目的成虫和幼虫，如盲蝽科的盲蝽、蝉科的蝉、大叶蝉科的叶蝉(例如Empoasca spp.)、蜡蝉科和飞虱科的飞虱、角蝉科的角蝉、木虱科的木虱、粉虱科的粉虱、蚜科的蚜虫、根瘤蚜科的根瘤蚜、粉蚧科的粉蚧、蚧科、盾蚧科和绵蚧科的介壳虫(scales)、网蝽科的网蝽、蝽科的蝽象、长蝽科的麦长蝽(例如Blissus spp.)和其它实蝽、沫蝉科的沫蝉、缘蝽科的南瓜缘蝽，以及红蝽科的红椿和棉红蝽；螨目的成虫和幼虫，如叶螨科的蛛螨和红蜘蛛(例如欧洲红蜘蛛(Panonychus ulmiKoch)、红蜘蛛(Tetranychus urticae Koch)、McDaniel螨(Tetranychusmcdaniele McGregor))、毛足蛛科(tenuipalpidae)的flat mite(例如桔短须螨(Brevipalpus lewisi McGregor))、瘿螨科(Erophyidae)的桔叶刺瘿螨和bud mites，以及其它摄叶螨；直翅目的成虫和幼虫，包括蚱蜢、蝗虫和蟋蟀(例如迁徙蚱蜢(例如Melanoplus sanguinipes Fabricius，M.differentialis Thomas)、美洲蚱蜢(例如Schistocerca americanaDrury)、沙漠蝗(Schistocerca gregaria Forskal)、迁徙蝗虫(Locustamigratoria L.)、蝼蛄(Gryllotalpa spp.))；双翅目的成虫和幼虫，包括潜叶虫、蠓、果蝇(实蝇科)、瑞典杆蝇(例如Oscinella frit L.)、soil maggot以及其它长角亚目；缨翅目的成虫和幼虫，包括葱蓟马(Thrips tabaciLindeman)和其它摄叶蓟马；蚰蜒目的蜈蚣；线虫门或纲的成员，包括如下重要的农业害虫，如根结线虫(Meloidogyne)属的根癌线虫、短体线虫(Pratylenchus)属的根斑线虫、毛刺线虫属(Trichodorus)的粗短根线虫。 Coleoptera larvae and adults leaf photo, including horned Curculionidae, Bruchidae and Curculionidae weevils (such as boll weevil (Anthonomus grandisBoheman), rice water weevil (Lissorhoptrus oryzophilus Kuschel), rice weevil insects (Sitophilus oryzae L.)); Chrysomelidae the flea beetle, yellow melon, insectivorous, leaf beetles, potato beetle and leaf miner (eg potato beetle (Leptinotarsa ​​decemlineata Say), corn rootworm (Diabrotica virgifera LeConte)); scarab and other beetles scaribaeidae (eg Lai Japanese beetle (Popillia japonica Newman) and European beetles (Rhizotrogusmajalis Razoumowsky)); kowtow A Division of wireworms and tibial spine Branch beetles beetles; leather winged adults and larvae purpose, including ball Sou Branch earwigs (for example the European earwigs (Forficulaauricularia L), black earwig (Chelisoches morio Fabricius)); Hemiptera and Homoptera adults and larvae, as Miridae of bugs, cicadas cicada Branch big leaf cicadidae leafhoppers (eg Empoasca spp.), and planthopper planthopper Fulgoroidea Branch Branch angle corner cicada cicada Branch, Division psyllid psyllids, whiteflies whiteflies and aphids aphids, phylloxera Branch phylloxera aphid, mealybug mealybugs Branch, Kuwana Branch, Diaspididae and cotton Kuwana Branch scale insects (scales), net Pentatomidae of lace bug, Pentatomidae the stinkbug, long Pentatomidae wheat long bug and other real bugs, Cercopidae of spittlebugs, Coreidae pumpkin Rhamnomia and red Pentatomidae of toon and cotton red bugs (eg Blissus spp.); mites purposes adults and larvae, as Tetranychidae of spider mites and Starscream (such as the European red mite (Panonychus ulmiKoch), spider mite (Tetranychus urticae Koch), McDaniel mite (Tetranychusmcdaniele McGregor)), hairy spider foot Branch (tenuipalpidae) of flat mite (eg orange Brevipalpus (Brevipalpus lewisi McGregor)) , Eriophyidae (Erophyidae) orange leaf gall mite thorns and bud mites, spider mites and other camera; Orthoptera adults and larvae, including grasshoppers, locusts and crickets (eg, migratory grasshoppers (eg Melanoplus sanguinipes Fabricius, M.differentialis Thomas ), American grasshoppers (eg Schistocerca americanaDrury), desert locust (Schistocerca gregaria Forskal), migratory locust (Locustamigratoria L.), mole crickets (Gryllotalpa spp));. Diptera adults and larvae, including leaf miner, midges, flies (Tephritidae), Sweden rod flies (eg Oscinella frit L.), soil maggot and other horned suborder; Thysanoptera purpose of adults and larvae, including onion thrips (Thrips tabaciLindeman) and other camera leaf thrips; Youyan purpose nematode door or classes of members, including the following important agricultural pests, such as root-knot nematode (Meloidogyne) belong to root knot nematodes, Pratylenchus (Pratylenchus) genus root nematodes spots, burrs nematode genera (Trichodorus) stubby; centipede root nematodes.

本领域技术人员将认识到，并非所有的化合物对所有的害虫有相同的效力。 Those skilled in the art will recognize that not all compounds have the same effect on all the pests. 本发明的化合物对下列目的害虫具有特别高的活性：鳞翅目(例如棉叶波纹夜蛾(Alabama argillacea Hübner)、果黄卷蛾(Archipsargyrospila Walker)、European leaf roller(A.rosana L.)和其它黄卷蛾(Archips)种、二化螟(Chilo suppressalis Walker)、稻纵卷叶螟(Cnaphalocrosis medinalis Guenee)、玉米根草螟(Crambuscaliginosellus Clemens)、早熟禾草螟(Crambus teterrellus Zincken)、苹果蠹蛾(Cydia pomonella L.)、鼎点金刚钻(Earias insulana Boisduval)、埃及金刚钻(Earias vittella Fabricius)、Ammerican bollworm(Helicoverpa armigera Hübner)、玉米穗蛾(Helicoverpa zea Boddie)、菸夜蛾(Heliothis virescens Fabricius)、苍螟(Herpetogramma licarsisalisWalker)、葡萄小食心虫(Lobesia botrana Denis &amp; Schiffermüller)、棉红铃虫(Pectinophora gossypiella Saunders)、桔细潜蛾(Phyllocnistiscitrella Stainton)、大菜粉蝶(Pieris brassicae L.)、小菜粉蝶(Pieris rapaeL.)、菜蛾(Plutella xylostella L.)、甜菜夜蛾(Spodoptera exigua Hübner)、斜纹夜蛾(Spodoptera litura Fabricius)、草地粘虫(Spodopterafrugiperda JESmith)、粉纹夜蛾(Trichoplusia ni Hübner)和tomatoleafminer(Tuta absoluta))。 The compounds of this invention for the following purposes pests particularly high activity: Lepidoptera (eg cotton leaves ripple armyworm (Alabama argillacea Hübner), yellow fruit moth (Archipsargyrospila Walker), European leaf roller (A.rosana L.) and Other yellow moth (Archips) species, stem borer (Chilo suppressalis Walker), leafroller (Cnaphalocrosis medinalis Guenee), corn grass root borer (Crambuscaliginosellus Clemens), early maturing grasses borer (Crambus teterrellus Zincken), codling moth (Cydia pomonella L.), Ding-point diamond (Earias insulana Boisduval), Egypt diamond (Earias vittella Fabricius), Ammerican bollworm (Helicoverpa armigera Hübner), corn earworm (Helicoverpa zea Boddie), tobacco budworm (Heliothis virescens Fabricius) Cang borer (Herpetogramma licarsisalisWalker), grape borer (Lobesia botrana Denis & amp; Schiffermüller), pink bollworm (Pectinophora gossypiella Saunders), orange fine leafminer (Phyllocnistiscitrella Stainton), large Pieris (Pieris brassicae L.), Pieris rapae (Pieris rapaeL.), diamondback moth (Plutella xylostella L.), beet armyworm (Spodoptera exigua Hübner), cutworm (Spodoptera litura Fabricius), fall armyworm (Spodopterafrugiperda JESmith), cabbage looper (Trichoplusia ni Hübner) and tomatoleafminer (Tuta absoluta)). 本发明的化合物对同翅目的成员也具有商业上重要的活性，所述同翅目包括：豌豆蚜(Acyrthisiphon pisumHarris)、豇豆蚜(Aphis craccivora Koch)、蚕豆蚜(Aphis fabae Scopoli)、棉蚜(Aphis gossypii Glover)、苹蚜(Aphis p0omi De Geer)、锈线菊蚜(Aphis spiraecola Patch)、指顶花无网蚜(Aulacorthum solaniKaltenbach)、草莓中瘤钉毛蚜(Chaetosiphon fragaefolii Cockerell)、俄罗斯麦长管蚜(Diuraphis noxia Kurdjumov/Mordvilko)、车前圆尾蚜(Dysaphis plantaginea Paaserini)、苹绵蚜(Eriosoma lanigerumHausmann)、桃大尾蚜(Hyalopterus pruni Geoffroy)、芜菁蚜(Lipaphiserysimi Kaltenbach)、谷蚜(Metopolophium dirrhodum Walker)、马铃薯长管蚜(Macrosipum euphorbiae Thomas)、桃蚜(Myzus persicae Sulzer)、莴苣衲长管蚜(Nasonovia ribisnigri Mosley)、根蚜和葡糖根疣蚜(Pemphigus spp.)、玉米蚜(Rhopalosiphum maidis Fitch)、bird cherry-oataphid(Rhopalosiphum padi L.)、麦二叉蚜(Schizaphis graminumRondani)、麦长管蚜(Sitobion avenae Fabricius)、苜蓿斑蚜(Therioaphismaculata Buckton)、桔声蚜(Toxoptera aurantii Boyer de Fonscolombe)、热带桔二岔蚜(Toxoptera citricida Kirkaldy)；球蚜(Adelges spp)；美核桃根瘤蚜(Phylloxera devastatrix Pergande)；烟草粉虱(Bemisia tabaciGennadius)、甘薯粉虱(Bemisia argentifolii Bellows &amp; Perring)、柑桔粉虱(Dialeurodes citri Ashmead)和温室粉虱(Trialeurodes vaporariorumWestwood)；马铃薯微叶蝉(Empoasca fabae Harris)、小褐稻虱(Laodelphax striatellus Fallen)、六点叶蝉(Macrolestes quadrilineatusForbes)、茶微叶蝉(Nephotettix cinticeps Uhler)、黑尾叶蝉(Nephotettixnigropictus Stl)、稻褐飞虱(Nilaparvata lugens Stl)、玉米蜡蝉(Peregrinus maidis Ashmead)、白背稻虱(Sogatella furcifera Horvath)、rice delphacid(Sogatodes orizicola Muir)、苹白小叶蝉(Typhlocybapomaria McAtee)、葡糖斑叶蝉(Erythroneoura spp.)；期蝉(Magicidadaseptendecim L.)、吹绵蚧(Icerya purchasi Maskell)；梨圆盾蚧(Quadraspidiotus perniciosus Comstock)；柑桔粉蚧(Planococcus citriRisso)；其它粉蚧复合体(Pseudococcus spp.)；梨黄木虱(Cacopsyllapyricola Foerster)、柿木虱(Trioza diospyri Ashmead)。 Compounds of the invention of the Homoptera members also have important commercial activity on the Homoptera include: pea aphid (Acyrthisiphon pisumHarris), cowpea aphid (Aphis craccivora Koch), broad bean aphid (Aphis fabae Scopoli), cotton aphid ( Aphis gossypii Glover), apple aphid (Aphis p0omi De Geer), Spiraea aphid (Aphis spiraecola Patch), foxglove aphid-free network (Aulacorthum solaniKaltenbach), strawberry aphid tumor nail hair (Chaetosiphon fragaefolii Cockerell), Eluosimai long aphid (Diuraphis noxia Kurdjumov / Mordvilko), before the car round aphid (Dysaphis plantaginea Paaserini), apple aphid (Eriosoma lanigerumHausmann), peach aphid (Hyalopterus pruni Geoffroy), turnip aphid (Lipaphiserysimi Kaltenbach), cereal aphid ( Metopolophium dirrhodum Walker), potato aphid (Macrosipum euphorbiae Thomas), green peach aphid (Myzus persicae Sulzer), cassock lettuce aphid (Nasonovia ribisnigri Mosley), root aphids and glucose warts root aphid (Pemphigus spp.), corn aphid (Rhopalosiphum maidis Fitch), bird cherry-oataphid (Rhopalosiphum padi L.), Schizaphis (Schizaphis graminumRondani), wheat aphid (Sitobion avenae Fabricius), spotted alfalfa aphid (Therioaphismaculata Buckton), orange sound aphid (Toxoptera aurantii Boyer de Fonscolombe), tropical orange Ercha aphid (Toxoptera citricida Kirkaldy); ball aphid (Adelges spp); US walnut phylloxera (Phylloxera devastatrix Pergande); Silverleaf whitefly (Bemisia tabaciGennadius), sweet potato whitefly (Bemisia argentifolii Bellows & amp; Perring), citrus whitefly (Dialeurodes citri Ashmead) and greenhouse whitefly (Trialeurodes vaporariorumWestwood); potato leafhopper (Empoasca fabae Harris), small brown planthopper (Laodelphax striatellus Fallen), aster leafhopper (Macrolestes quadrilineatusForbes), tea leafhopper (Nephotettix cinticeps Uhler), leafhopper (Nephotettixnigropictus Stl), brown planthopper (Nilaparvata lugens Stl), corn planthoppers (Peregrinus maidis Ashmead), white-backed planthopper (Sogatella furcifera Horvath), rice delphacid (Sogatodes orizicola Muir), small white apple leafhopper (Typhlocybapomaria McAtee), glucose leafhopper (Erythroneoura spp.); of cicada (Magicidadaseptendecim L.), Icerya (Icerya purchasi Maskell); pear Buckler Kuwana ( Quadraspidiotus perniciosus Comstock); citrus mealybug (Planococcus citriRisso); other mealybug complex (Pseudococcus spp);. pear psylla (Cacopsyllapyricola Foerster), persimmon psyllid (Trioza diospyri Ashmead). 这些化合物还对半翅目的成员有活性，所述半翅目包括：稻绿蝽(Acrosternum hilareSay)、南瓜绿蝽(Anasa tristis De Geer)、麦长蝽(Blissus leucopterusSay)、棉网蝽(Corythuca gossypii Fabricius)、tomato bug(Cyrtopeltismodesta Distant)、棉黑翅红蝽(Dysdercus suturellus Herrich-Schffer)、褐臭蝽(Euchistus servus Say)、一点褐蝽(Euchistus variolarius Palisotde Beauvois)、地长蝽属(Graptosthetus spp)、松籽喙缘蝽(Leptoglossuscorculus Say)、牧草盲蝽(Lygus lineolaris Palisot de Beauvois)、稻绿蝽(Nezara viridula L.)、稻褐蝽(Oebalus pugnax Fabricius)、大马利筋长蝽(Oncopeltus fasciatuf Dallas)、棉跳盲蝽(Pseudatomoscelis seriatusReuter)。 These compounds are also active Hemiptera, the Hemiptera include: rice green stink bug (Acrosternum hilareSay), pumpkin green stink bug (Anasa tristis De Geer), wheat long bug (Blissus leucopterusSay), cotton lace bug (Corythuca gossypii Fabricius), tomato bug (Cyrtopeltismodesta Distant), black-winged red cotton bug (Dysdercus suturellus Herrich-Schffer), brown stink bug (Euchistus servus Say), a little brown bugs (Euchistus variolarius Palisotde Beauvois), to long bug genus (Graptosthetus spp), pine beak Rhamnomia (Leptoglossuscorculus Say), tarnished plant bug (Lygus lineolaris Palisot de Beauvois), rice green stink bug (Nezara viridula L.), brown rice stink bug (Oebalus pugnax Fabricius), large milkweed bug long ( Oncopeltus fasciatuf Dallas), cotton jump bugs (Pseudatomoscelis seriatusReuter). 由本发明的化合物防治的其他昆虫目包括缨翅目(例如苜蓿蓟马(Frankliniella occidentalis Pergande)、桔实蓟马(Scirthothrips citriMoulton)、大豆蓟马(Sericothrips variabilis Beach)和葱蓟马(Thripstabaci Lindeman))，以及鞘翅目(例如马铃薯甲虫(Leptinotarsadecemlineata Say)、墨西哥豆瓢虫(Epilachna varivestis Mulsant)和Agriotes、Athous或Limonius属的金针虫)。 Other compounds from the insect prevention purposes of the invention include Thysanoptera (eg thrips (Frankliniella occidentalis Pergande), orange solid thrips (Scirthothrips citriMoulton), soybean thrips (Sericothrips variabilis Beach) and onion thrips (Thripstabaci Lindeman)) and Coleoptera (eg potato beetle (Leptinotarsadecemlineata Say), Mexican bean beetle (Epilachna varivestis Mulsant) and Agriotes, Athous or Limonius genus wireworms).

本发明的方法实际上可用于所有植物品种。 The method of the present invention can be used in virtually all plant species. 可处理的种子包括，例如小麦(Triticum aestivum L.)、硬质小麦(Triticum durum Desf.)、大麦(Hordeum vulgare L.)、燕麦(Avena sativa L.)、黑麦(Secale cerealeL.)、玉米(Zea may L.)、高梁(Sorghum vulgare Pers.)、稻(Oryza sativaL.)、茭白(Zizania aquatica L.)、棉花(Gossypium barbadense L和G.hirsutum L)、亚麻(Linum usitatissimum L.)、向日葵(Helianthus annuusL.)、大豆(Glycine max Merr.)、四季豆(Phaseolus vulgaris L.)、菜豆(Phaseolus limensis Macf.)、蚕豆(Vicia faba L.)、豌豆(Pisum sativumL.)、花生(Arachis hypogaes L.)、苜蓿(Medicago sativa L.)、甜菜(Betavulgaris L.)、莴苣(Lactuca sativa L.)、油菜籽(Brassica rapa L.和B.napus L.)、甘蓝作物如卷心菜、花椰菜和椰菜(Brassica oleracea L.)、芜菁(Brassica rapa L.)、芥菜(Brassica juncea Coss.)、黑芥(Brassicanigra Koch)、番茄(Lycopersicon esculentum Mill)、马铃薯(Solanumtuberosum L.)、胡椒(Capsicum frutescens L.)、茄子(Solanum melongenaL.)、烟草(Nicotiana tabacum L.)、黄瓜(Cucumis sativus L.)、香瓜(Cucumis melo L.)、西瓜(Citrullus vulgaris Schrad)、南瓜(Curcurbitapepo L.，C.moschata Duchesne和C.maxima Duchesne)、胡萝卜(Daucus carota L.)、百日菊(Zinnia elegans Jacq.)、大波斯菊(例如Cosmos bipinnatus Cav.)、菊花(Chrysanthemum spp.)、非洲菊(Scabiosaatropurpurea L.)、金鱼草(Antirrhinum majus L.)、大丁草(Gerberajamesonii Bolus)、满天星(Gypsophila paniculata L.，G.repens L.和G.elegans Gieb.)、补血草(例如Limonium sinuatum Mill.，L sinenseKuntze)、矮百合(例如Liatris spicata Willd.，L.pycnostachya Michx.，L.scariosa Willd)、洋桔梗(例如Eustoma grandiflorum(Raf.)Shinn)、西洋蓍草(例如Achillea filipendulina Lam.，A.millefolium L.)、万寿菊(例如Tagetes patula L.，T.erecta L.)、三色堇(例如Viola cornuta L.，V.tricolor L.)、凤仙花(例如Impatiens balsamina L.)、矮牵牛花(Petuniaspp.)、天竺葵(Geranium spp.)和紫锦苏(例如Solenostemonscutellarioides(L.)Codd)。 Seed treatment may include, for example, wheat (Triticum aestivum L.), durum wheat (Triticum durum Desf.), Barley (Hordeum vulgare L.), oat (Avena sativa L.), rye (Secale cerealeL.), Corn (Zea may L.), sorghum (Sorghum vulgare Pers.), rice (Oryza sativaL.), wild rice (Zizania aquatica L.), cotton (Gossypium barbadense L and G.hirsutum L), flax (Linum usitatissimum L.), Sunflowers (Helianthus annuusL.), soybean (Glycine max Merr.), green beans (Phaseolus vulgaris L.), common bean (Phaseolus limensis Macf.), beans (Vicia faba L.), pea (Pisum sativumL.), peanuts (Arachis hypogaes L.), alfalfa (Medicago sativa L.), sugar beet (Betavulgaris L.), lettuce (Lactuca sativa L.), rapeseed (Brassica rapa L. and B.napus L.), cabbage crops such as cabbage, broccoli and broccoli (Brassica oleracea L.), turnip (Brassica rapa L.), mustard (Brassica juncea Coss.), black mustard (Brassicanigra Koch), tomato (Lycopersicon esculentum Mill), potato (Solanumtuberosum L.), pepper (Capsicum frutescens L.), eggplant (Solanum melongenaL.), tobacco (Nicotiana tabacum L.), cucumber (Cucumis sativus L.), melon (Cucumis melo L.), watermelon (Citrullus vulgaris Schrad), pumpkin (Curcurbitapepo L., C .moschata Duchesne and C.maxima Duchesne), carrot (Daucus carota L.), Zinnia (Zinnia elegans Jacq.), cosmos (such as Cosmos bipinnatus Cav.), chrysanthemum (Chrysanthemum spp.), Gerbera (Scabiosaatropurpurea L.), snapdragon (Antirrhinum majus L.), Gerbera (Gerberajamesonii Bolus), baby's breath (Gypsophila paniculata L., G.repens L. and G.elegans Gieb.), blood grass (such as Limonium sinuatum Mill ., L sinenseKuntze), dwarf lily (eg Liatris spicata Willd., L.pycnostachya Michx., L.scariosa Willd), lisianthus (eg Eustoma grandiflorum (Raf.) Shinn), yarrow (such as Achillea filipendulina Lam., A.millefolium L.), marigold (such as Tagetes patula L., T.erecta L.), pansy (such as Viola cornuta L., V.tricolor L.), impatiens (such as Impatiens balsamina L.) , petunia (Petuniaspp.), geranium (Geranium spp.) and purple Jin Su (eg Solenostemonscutellarioides (L.) Codd). 不仅种子，而且它们的根茎、块茎、鳞茎或球茎，包括活的插条，均可根据本发明进行处理，如来自马铃薯(Solanum tuberosum L.)、甘薯(Ipomoea batatas L.)、山药(Dioscoreacayenensis Lam.和D.roundata Poir)、洋葱(例如Allium cepa L.)、郁金香(Tulipa spp.)、唐菖蒲(Gladiolus spp.)、百合(Lilium spp.)、水仙(Narcissus spp.)、大丽花(例如Dahlia pinnata Cav.)、鸢尾(Irisgermanica L.和其它品种)、藏红花(Crocus spp.)、银莲花(Anemonespp.)、风信子(Hyacinth spp.)、麝香兰(Muscari spp.)、小苍兰(例如Freesia refracta Klatt.，F.armstrongii W.Wats)、观赏洋葱(Alliumspp.)、酢浆草(Oxalis spp.)、红海葱(Scilla peruviana L.和其它品种)、仙客来(Cyclamen persicum Mill.和其它品种)、四萼齿草(Chionodoxaluciliae Boiss和其它品种)、条纹红海葱(Puschkinia scilloides Adams)、水芋百合(calla lily)(Zantedeschia aethiopica Spreng.，Z.elliottianaEngler和其它品种)、大岩桐(Sinnigia speciosa Benth.&amp; Hood.)和块茎状秋海棠(Begonia tuberhybrida Voss.)。 Not only seeds, and their roots, tubers, bulbs or corms, including viable cuttings, can be processed according to the present invention, such as from potato (Solanum tuberosum L.), sweet potato (Ipomoea batatas L.), yam (Dioscoreacayenensis Lam . and D.roundata Poir), onion (such as Allium cepa L.), tulips (Tulipa spp.), gladiolus (Gladiolus spp.), Lily (Lilium spp.), narcissus (Narcissus spp.), Dahlia (eg Dahlia pinnata Cav.), Iris (Irisgermanica L. and other species), saffron (Crocus spp.), Anemone (Anemonespp.), Hyacinth (Hyacinth spp.), musk orchid (Muscari spp.), freesia (eg Freesia refracta Klatt., F.armstrongii W.Wats), ornamental onion (Alliumspp.), oxalis (Oxalis spp.), Red onion (Scilla peruviana L. and other species), cyclamen (Cyclamen persicum Mill. and Other varieties), four calyx teeth grass (Chionodoxaluciliae Boiss and other species), striped Red onions (Puschkinia scilloides Adams), Calla Lily (calla lily) (Zantedeschia aethiopica Spreng., Z.elliottianaEngler and other varieties), Sinningia (Sinnigia speciosa . Benth & amp;. Hood) and tuberous begonias (Begonia tuberhybrida Voss).. 可以根据本发明处理茎插，包括来自如下植物的茎插：甘蔗(Saccharum officinarum L.)、香石竹(Dianthus caryophyllus L.)、florists chrysanthemum(Chrysanthemummortifolium Ramat.)、秋海棠(Begonia spp.)、天竺葵(Geranium spp.)、紫锦苏(例如Solenostemon scutellarioides(L.)Codd)和一品红(Euphorbia pulcherrima Willd.)。 According to the present invention can handle stem is inserted, including those from the following plant stems inserted: (. Dianthus caryophyllus L) (. Begonia spp) sugarcane (Saccharum officinarum L.), carnation, florists chrysanthemum (. Chrysanthemummortifolium Ramat), begonia, geranium ( Geranium spp.), Zi Jin Su (eg Solenostemon scutellarioides (L.) Codd) and poinsettia (Euphorbia pulcherrima Willd.). 可以根据本发明处理的叶插包括来自如下植物的页插：秋海棠(Begonia spp.)、非洲堇(例如Saintpauliaionantha Wendl.)和景天(Sedum spp.)。 According to the present invention can be inserted leaf processing plants, including pages from the following insert: (. Begonia spp) (. For example Saintpauliaionantha Wendl) begonia, African violet and sedum (Sedum spp.). 上面列举的谷类、蔬菜、观赏植物(包括花)和果实作物是说明性的，不应认为它们以任何方式限制本发明。 Listed above cereals, vegetables, ornamentals (including flower) and fruit crops are illustrative, they should not be considered in any way limiting the present invention. 因为无脊椎害虫防治谱和经济重要性，棉花、玉米、大豆和稻的种子处理，马铃薯、甘薯、洋葱、郁金香、水仙、番红花和风信子的块茎和鳞茎处理是本发明的优选实施方案。 Because invertebrate pest control spectrum and economic importance, seed cotton, corn, soybeans and rice processing, potatoes, sweet potatoes, onions, tulips, daffodils, crocuses and hyacinths tubers and bulbs deal is a preferred embodiment of the present invention.

可以通过多种不同方法来用式I的化合物处理繁殖体的场所。 Can be disposal sites propagules compound of formula I by means of various methods. 所需的全部就是生物有效量的式I的化合物，其被施加于或足够靠近繁殖体，从而使其能被该繁殖体吸收。 All that is biologically effective amount of a compound of formula I required, which is applied on or sufficiently close to the propagule so that it can absorb the propagules. 式I的化合物可以通过以下方法施用：用式I的化合物的溶液或分散体浸透包含繁殖体的生长介质，混合式I的化合物与生长介质并在经处理的生长介质中种植该繁殖体(例如育苗箱处理)，或者各种形式的繁殖体处理，其中在将繁殖体种植在生长介质中之前将式I的化合物施用于繁殖体。 Compounds of formula I may be administered by the following method: a solution or dispersion of compounds of formula I impregnated with growth medium containing propagules, compound of formula I mixed with the growth medium and the cultivation of propagules in the treated growing medium (e.g. nursery box treatment), or various forms of propagule treatment, wherein the propagules planted in a compound of formula I is administered to the growth medium prior propagules.

在这些方法中，式I的化合物将通常与农业上适宜的载体一起以配方或组合物来施用，所述适宜的载体包含至少一种液体稀释剂、固体稀释剂或表面活性剂。 In these methods, compounds of formula I will generally together to formulations or compositions to be administered with an agriculturally suitable carrier, said suitable carrier comprises at least one liquid diluent, a solid diluent or a surfactant. 多种配方适用于本发明，最适宜的配方取决于施用方法。 A variety of formulations suitable for the present invention, the most suitable formulation depending on the method of application. 如本领域技术人员熟知的，配方的目的是提供安全和便利的转运、测量、分配作物保护化学品的方式，还有优化其生物功效。 As well known to those skilled in the purpose of formulation is to provide a safe and convenient transport, measuring, crop protection chemicals are allocated, as well as to optimize the biological efficacy.

取决于施用方法，有用的配方包括液体如溶液剂(包括乳状浓缩物)、混悬剂、乳剂(包括微乳和/或悬乳(suspoemulsions))等，它们可以任选地被浓缩成凝胶。 Depending on the method of application useful formulations include liquids such as solutions (including emulsion concentrates), suspensions, emulsions (including microemulsions and / or suspended milk (suspoemulsions)), etc., which may optionally be concentrated to a gel . 有用的配方进一步包括固体如粉剂、散剂、颗粒剂、丸剂、片剂、膜剂等，它们可以是水分散性的(“可湿性的”)或水溶性的。 Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, etc., which can be water-dispersible ("wettable") or water-soluble. 可以将有效成分(微)胶囊化并进一步形成混悬剂或固体配方；或者可以将有效成分的整个配方胶囊化(或“包衣”)。 The active ingredient can be (micro) encapsulated and further formed a suspension or solid formulation; or may be the entire formulation of active ingredient encapsulated (or "coating"). 胶囊化可以控制或延缓有效成分的释放。 Encapsulation can control or delay the release of the active ingredient. 可喷雾的配方可以在适宜的介质中提供，使用的喷雾体积为每公顷约一百至几百升。 Sprayable formulations can be provided in a suitable medium, the spray volume per hectare is used from about one hundred to several hundred liters. 高强度组合物主要用作进一步配方的中间体。 High strength compositions are primarily used as intermediates for further formulation.

配方通常含有有效量的有效成分、稀释剂和表面活性剂，大约在如下范围内，它们总和为100重量％。 Formulations typically contain an effective amount of the active ingredient, diluent and surfactant within the following range of about, they sum to 100% by weight.

重量百分比有效成分稀释剂表面活性剂水分散性和水溶性颗粒 5-90 0-94 1-l5剂、片剂和散剂混悬剂、乳剂、溶液剂 5-50 40-95 0-15(包括乳状浓缩物)粉末 1-25 70-99 0-5颗粒剂与丸剂 0.01-99 5-99.99 0-15高强度组合物 90-99 0-10 0-2典型的固体稀释剂在Watkins等人，Handbook of Insecticide DustDiluents and Carriers，第二版，Dorland Books，Caldwell，New Jersey中有描述。 Weight percent active ingredient surfactant diluent water-dispersible and water-soluble granules 5-90 0-94 1-l5, tablets, and powders, suspensions, emulsions, solutions 5-5040-950-15 (including emulsion concentrates) powder 1-2570-990-5 granules and pellets 0.01-99 5-99.99 0-15 High strength compositions 90-990-100-2 Typical solid diluents are described in Watkins, et al., Handbook of Insecticide DustDiluents and Carriers, Second Edition, Dorland Books, Caldwell, New Jersey are described. 典型的液体稀释剂在Marsden，Solvents Guide，第二版，Interscience，New York，1950中有描述。 Typical liquid diluents are described in Marsden, Solvents Guide, Second Edition, Interscience, New York, 1950 are described. McCutcheon's Emulsifiers andDetergents and McCutcheon's Functional Materials(North America andInternational Edition，2001)，The Manufactuing Confection Publ Co.，Glen Rock，New Jersey，以及Sisely and Wood，Encyclopedia of SurfaceActive Agents，Chemical Publ.Co.，Inc.，New York，1964列出了表面活性剂和推荐的应用。 McCutcheon's Emulsifiers andDetergents and McCutcheon's Functional Materials (North America andInternational Edition, 2001), The Manufactuing Confection Publ Co., Glen Rock, New Jersey, and Sisely and Wood, Encyclopedia of SurfaceActive Agents, Chemical Publ.Co., Inc., New York , 1964, list surfactants and recommended application. 所有配方都可以含有少量添加剂以减少泡沫。 All formulations can contain minor amounts of additives to reduce foam. 结块、腐蚀、微生物生长等，或者含有增稠剂以增加粘度。 Caking, corrosion, microbiological growth, etc., or contain a thickening agent to increase the viscosity.

表面活性剂包括，例如，乙氧基化醇、乙氧基化烷基酚、乙氧基化脱水山梨糖醇脂肪酸酯、乙氧基化胺、乙氧基化脂肪酸、酯和油、磺基丁二酸二烷基酯、烷基硫酸盐、烷基芳基磺酸盐、有机硅酮、N，N-二烷基牛磺酸盐、乙二醇酯、磷酸酯、木质素磺酸盐、萘磺酸盐甲醛缩合物、聚羧酸盐和包括聚氧乙烯/聚氧丙烯嵌段共聚物在内的嵌段共聚物。 Surfactants include, for example, ethoxylated alcohols, ethoxylated alkylphenols, ethoxylated sorbitan fatty acid esters, ethoxylated amines, ethoxylated fatty acids, esters and oils, sulfonic succinic acid dialkyl ester, alkyl sulfates, alkyl aryl sulfonates, organic silicone, N, N- dialkyl taurates, glycol esters, phosphate esters, lignin sulfonic acid salts, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and include polyoxyethylene / polyoxypropylene block copolymers, including block copolymers. 固体稀释剂包括，例如，粘土如膨润土、蒙脱石、硅镁土和高岭土、淀粉、糖、二氧化硅、滑石、硅藻土、尿素、碳酸钙、碳酸钠和碳酸氢钠，以及硫酸钠。 Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate . 液体稀释剂包括，例如，水、N，N-二甲基甲酰胺、二甲基亚砜、N-烷基吡咯烷酮、乙二醇、聚丙二醇、丙烯碳酸酯、二元酯、石蜡、烷基苯、烷基萘、橄榄油、蓖麻油、亚麻籽油、桐油、芝麻油、玉米油、花生油、棉籽油、大豆油、菜籽油和椰子油、脂肪酸酯、酮类如环己酮、2-庚酮、异佛乐酮和4-羟基-4-甲基-2-戊酮，以及醇类如甲醇、环己醇、十二烷基醇、苄醇和四氢呋喃醇。 Liquid diluents include, for example, water, N, N- dimethylformamide, dimethyl sulfoxide, N- alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffins, alkyl benzene, alkyl naphthalene, olive oil, castor oil, linseed oil, tung oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil and coconut oil, fatty acid esters, ketones such as cyclohexanone, 2 - heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, lauryl alcohol, benzyl alcohol and tetrahydrofurfuryl alcohol.

溶液，包括乳状浓缩物，可以简单地通过混合各组分来制备。 Solution, including emulsion concentrates, can be prepared by simply mixing the ingredients. 细粉和粉末可以通过混合，并且通常在锤式粉碎机或流能磨中进行研磨而制备。 And fine powders may be prepared by mixing, and is usually prepared by grinding in a hammer mill or fluid energy mill. 悬浮剂通常通过湿磨而制备；参见例如，US3,060,084。 Suspending agent is typically prepared by wet-milling; see, for example, US3,060,084. 颗粒剂和丸剂可以通过将活性物质喷在预制成的颗粒载体上或者通过团聚技术来制备。 Granules and pellets can be prepared by spraying the active material on preformed granular carriers or by agglomeration techniques be prepared. 参见Browning，“Agglomeration”，ChemicalEngineering，1967年12月4日，第147-48页；Perry's ChemicalEngineer's Handbook，第四版，McGraw-Hill，New York，1963 8-57页和下述的，以及PCT公开WO 91/13546。 See Browning, "Agglomeration", ChemicalEngineering, 1967 年 12 4, p. 147-48; Perry's ChemicalEngineer's Handbook, Fourth Edition, McGraw-Hill, New York, 1963 8-57 and the following pages, and PCT Publication WO 91/13546. 丸剂的制备如US4,172,714中所描述。 Pellets prepared as described in US4,172,714. 水分散性和水溶性粒剂可以根据US4,144,050、US3,920,442和DE 3,246,493所教导而制备。 Water-dispersible and water-soluble granules can be prepared according to US4,144,050, US3,920,442 and DE 3,246,493 teaches. 片剂可以根据US5,180,587、US5,232,701和US5,208,030所教导而制备。 Tablets according to the teachings of US5,180,587, US5,232,701 and US5,208,030 prepared. 膜剂可以根据GB 2,095,558和US3,299,566所教导而制备。 Agent can be prepared in accordance with the teachings of GB 2,095,558 and US3,299,566.

有关配方技术的更多信息，参见TSWoods，“The Formulator'sToolbox-Product Forms for Modern Agriculture”，收于PesticideChemistrv and Bioscience，The Food-Environment Challenge，T.Brooks和TRRoberts编著，Proceedings of the 9thInternational Congress onPesticide Chemistry，The Royal Society of Chemistry，Cambridge，1999，pp.120-133。 For more information about the formulation technology, see TSWoods, "The Formulator'sToolbox-Product Forms for Modern Agriculture", to close at PesticideChemistrv and Bioscience, The Food-Environment Challenge, T.Brooks and TRRoberts eds, Proceedings of the 9thInternational Congress onPesticide Chemistry , The Royal Society of Chemistry, Cambridge, 1999, pp.120-133. 另外参见US3,235,361，第6栏第16行至第7栏第19行及实施例10-41；US3,309,192，第5栏第43行至第7栏第62行及实施例8、12、15、39、41、52、53、58、132、138-140、162-164、166、167和169-182；US2,891,855，第3栏第66行至第5栏第17行及实施例1-4；Klingman，Weed Control as a Science，John Wiley andSons，Inc.，New York，1961，第81-96页；以及Hance等，Weed ControlHandbook，第8版，Blackwell Scientific Publications，Oxford，1989。 See also US3,235,361, line 16 to column 7, line 19, column 6, and Examples 10-41; US3,309,192, column 5, line 43 to column 7, line 62 and Examples 8, 12, 15,39,41,52,53,58,132,138-140,162-164,166,167 and 169-182; US2,891,855, column 3, line 66 to column 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley andSons, Inc., New York, 1961, on pages 81-96; and Hance, etc., Weed ControlHandbook, Version 8, Blackwell Scientific Publications, Oxford, 1989.

根据本发明，可以通过一种方法保护繁殖体或从其生长的植物免受无脊椎害虫侵害，所述方法包括使该繁殖体或该繁殖体的场所与包含生物有效量的式I的化合物、其N-氧化物或农业上适用的盐的组合物接触。 According to the present invention, may be protected by a method propagule or a plant grown therefrom from an invertebrate pests, said method comprising contacting the propagule or the properties of the propagule with a biologically effective amount of a compound comprising Formula I, Suitable salts of the compositions contacting the N- oxide thereof or agriculture. 本发明包括与包含生物有效量的式I的化合物、其N-氧化物或农业上适用的盐，以及有效量的至少一种其它生物活性化合物或试剂的组合物接触的繁殖体。 The present invention includes a compound comprising a biologically effective amount of a formula I, their N- oxide or agriculturally suitable salt thereof, and an effective amount of at least one propagules other biologically active compounds or agents of the composition of the contact. 根据本发明用于处理繁殖体(或从其生长的植物)的组合物也可以包含(除式I的成分之外)有效量的一种或多种其他生物活性化合物或试剂。 According to the present invention for treating propagules (or plant grown therefrom) of the composition may also contain (in addition to the Formula I component) an effective amount of one or more other biologically active compounds or agents. 适宜的其它化合物或试剂包括杀虫剂、杀菌剂、杀线虫剂、杀细菌剂、杀螨剂、生长调节剂如生根刺激剂、化学不育剂、半化学药物(semiochemical)、拒虫剂、诱虫剂、外激素、取食刺激剂、其它生物活性化合物或昆虫致病细菌、病毒或真菌，以形成多组分杀虫药，所述杀虫药给出更宽的农业效用谱。 Suitable other compounds or agents including insecticides, fungicides, nematicides, bactericides, acaricides, growth regulators such as rooting stimulants, chemosterilant, semi-chemicals (semiochemical), insect repellent, insect attractant, pheromones, feeding stimulants, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component insecticide, the insecticide is given a broader spectrum of agricultural utility. 这些可与本发明的化合物一起配方的生物活性化合物或试剂的实例为：杀虫剂如阿维菌素、乙酰甲胺磷、吡虫清、amidoflument(S-1955)、齐墩螨素、艾扎丁、谷硫磷、氟氯菊酯、binfenazate、噻嗪酮、呋喃丹、氟唑虫清、定虫隆、毒死蜱、甲基毒死蜱、环虫酰肼(chromafenozide)、噻虫胺、百树菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、灭蝇胺、溴氰菊酯、杀螨硫隆、二嗪农、氟脲杀、乐果、噁茂醚、依马菌素、硫丹、高氰戊菊酯、ethiprole、苯硫威、双氧威、甲氰菊酯、唑螨酯、杀灭菊酯、锐劲特、flonicamid、氟氰戊菊酯、氟胺氰菊酯、flufenerim(UR-50701)、氟虫脲、地虫磷、特丁苯酰肼、氟铃脲、吡虫啉、噁二唑虫、丙胺磷、氟丙氧脲、马拉硫磷、蜗牛敌、甲胺磷、杀扑磷、灭多虫、蒙五一五、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝虫噻嗪、双苯氟脲、noviflumuron(XDE-007)、甲氨叉威、对硫磷、甲基对硫磷、氯菊酯、甲拌磷、伏杀磷、亚胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蝇醚、鱼藤酮、艾克敌105、spiromesifin(BSN2060)、乙丙硫磷、双苯酰肼、伏虫隆、七氟菊酯、特丁磷、杀虫畏、噻虫啉(thiacloprid)、噻虫嗪(thiamethoxam)、硫双灭多威、杀虫双、四溴菊酯、敌百虫和杀虫隆；杀菌剂如噻二唑素、腈嘧菌酯、苯菌灵、灭瘟素、波尔多液(碱式硫酸铜)、糠菌唑、氯环丙酰胺、敌菌丹、克菌丹、多菌灵、地茂散、百菌清、王铜、铜盐、cyflufenamid、清菌脲、环唑醇、环丙嘧啶、(S)-3，5-二氯-N-(3-氯-1-乙基-1-甲基-2-氧丙基)-4-甲基苯甲酰胺(RH7281)、双氯氰菌胺(diclocymet)(S-2900)、哒菌清、氯硝胺、噁咪唑、(S)-3，5-二氢-5-甲基-2-(甲硫基)-5-苯基-3-(苯氨基)-4H-咪唑-4-酮(RP 407213)、烯酰吗啉、dimoxystrobin、烯唑醇、烯唑醇-M、多果定、克瘟散、氧唑菌、噁唑酮菌、咪唑菌酮(fenamidone)、异嘧菌醇、腈苯唑、fencaramid(SZX0722)、拌种咯、苯锈啶、丁苯吗啉、薯瘟锡、毒菌锡、氟啶胺、氟噁菌、氟联苯菌(RPA 403397)、flumorf/flumorlin(SYP-L190)、fluoxastrobin(HEC5725)、喹唑菌酮、氟硅唑、氟酰胺、粉唑醇、灭菌丹、藻菌磷、呋氨丙灵、呋吡唑灵(furametapyr)(S-82658)、己唑醇、环戊唑醇、异稻瘟净、异丙定、稻瘟灵、春雷霉素、亚胺菌、代森锰锌、代森锰、mefenxam、丙氧灭绣胺、甲霜灵、环戊唑菌、叉氨苯酰胺(SSF-126)、metrafenone(AC375839)、腈菌唑、田安甲胂铁(甲基胂酸铁)、nicobifen(BAS 510)、orysastrobin、噁霜灵、戊菌唑、戊菌隆、噻菌灵、丙氯灵、百维灵、丙环唑、proquinazid(DPX-KQ926)、prothioconazole(JAU6476)、啶斑肟、pyraclostrobin、二甲嘧菌胺、咯喹酮、喹氧灵、螺噁茂胺、硫、戊唑醇、氟醚唑、涕必灵、溴氟唑菌、甲基托布津、福美双、tiadinil、三唑酮、唑菌醇、三环唑、肟菌酯(trifloxystrobin)、戊叉唑菌、有效霉素和烯菌酮；杀线虫剂如涕灭威、甲氨叉威和克线磷；杀细菌剂如链霉素；杀螨剂如虫螨脒、灭螨猛、乙酯杀螨醇(chlorobenzilate)、三环锡、开乐散、除螨灵、特苯噁唑、喹螨醚、杀螨锡、甲氰菊酯、唑螨酯、噻螨酮、克螨特、哒螨酮和吡螨胺；和生物试剂如包括苏云金杆菌a和苏云金杆菌k在内的苏云金杆菌，苏云金杆菌δ-内毒素、杆状病毒，以及昆虫致病细菌、病毒和真菌。 Examples of these agents or bioactive compounds with compounds of the present invention are formulated together: insecticides such as abamectin, acephate, acetamiprid, amidoflument (S-1955), abamectin, Ai Zhading, azinphos-methyl, bifenthrin, binfenazate, buprofezin, carbofuran, chlorfenapyr, Chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, ring tebufenozide (chromafenozide), clothianidin, one hundred tree Permethrin, β- cyfluthrin, cyhalothrin, λ- cyhalothrin, cypermethrin, cyromazine, deltamethrin, mites sulfur Long, diazinon, fluorouracil kill, dimethoate, evil Mao ether, according to Ma streptozotocin, endosulfan, esfenvalerate, ethiprole, benzene, sulfur Viagra, fenoxycarb, fenpropathrin, Fenpyroximate, fenvalerate, fipronil, flonicamid, fluorine cyanide E Permethrin, fluvalinate, flufenerim (UR-50701), flufenoxuron, FONOFOS, halofenozide, hexaflumuron, imidacloprid, oxadiazole insects, propylamine phosphorus, fluorine propoxyphene urea, horses Pull parathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, monocrotophos, methicillin hydrazide, Nithiazine, novaluron, noviflumuron ( XDE-007), A fork ammonia Viagra, parathion, methyl parathion, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, refused triazine ketones, pyridalyl, pyriproxyfen, rotenone, spinosad 105, spiromesifin (BSN2060), ethylene-propylene parathion, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid (thiacloprid), thiamethoxam (thiamethoxam), sulfur double methomyl, Bisultap, tralomethrin, trichlorfon and insecticidal Long; fungicides such as acibenzolar, azoxystrobin, benomyl , blasticidin, Bordeaux mixture (basic copper sulfate), bromuconazole, chlorine cyproterone amide, captafol, captan, carbendazim, to Mao San, chlorothalonil, copper king, copper, cyflufenamid Qing iprodione, cyproconazole, cyclopropylmethyl pyrimidine, (S) -3,5- dichloro -N- (3- chloro-1-ethyl-1-methyl-2-oxopropyl) -4- dimethylbenzamide (RH7281), double cyanuric bacteria amine (diclocymet) (S-2900), Da Qing bacteria, chlorine Nitramine, oxpoconazole, (S) -3,5- dihydro-5-methyl - 2- (methylthio) -5-phenyl-3- (phenylamino) -4H--imidazol-4-one (RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole -M, more dodine, g blast scattered, epoxiconazole, oxazolone bacteria, fenamidone (fenamidone), iso triarimol, fenbuconazole, fencaramid (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, potato plague tin, tin toadstool, Fluazinam, fluorine bad bacteria, flurbiprofen bacteria (RPA 403397), flumorf / flumorlin (SYP-L190), fluoxastrobin (HEC5725), quinazolinone cycloheximide, Flusilazole, Flutolanil , Flutriafol, folpet, algae bacteria phosphorus, metalaxyl furosemide, furosemide pyrazole Spirit (furametapyr) (S-82658), Hexaconazole, cyclopentyl Hexaconazole, Iprobenfos, isopropyl fixed, rice Isoprothiolane, kasugamycin, imine bacteria, mancozeb, maneb, mefenxam, propoxyphene off embroidered amine, metalaxyl, metconazole, fork benzamide (SSF-126), metrafenone (AC375839 ), myclobutanil, Tian A arsine iron (methyl arsenic acid iron), nicobifen (BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, thiabendazole, prochloraz, one hundred spiritual dimension, propiconazole, proquinazid (DPX-KQ926), prothioconazole (JAU6476), pyrifenox, pyraclostrobin, dimethyl mepanipyrim, pyroquilon, quinoxyfen, snails dioxolyl amines, sulfur, tebuconazole, desflurane azole , thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, triadimefon, azole bacteria alcohol, Tricyclazole, trifloxystrobin (trifloxystrobin), E fork azole bacteria, fungi and allyl validamycin ketone; nematicides such as aldicarb, A fork Granville ammonia and phosphorus grams line; bactericides such as streptomycin; acaricides such as amitraz, Chinomethionate, mites ethyl alcohol (chlorobenzilate), tricyclic tin, dicofol, mites and spirit, especially benzene, oxazole, Fenazaquin, mites tin, fenpropathrin, Fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological reagents such as including a Bacillus thuringiensis and Bacillus thuringiensis k including Bacillus thuringiensis, Bacillus thuringiensis toxins within δ-, baculovirus and insect pathogenic bacteria, viruses and fungi.

有关这些农用保护剂的通用参考文献是The Pesticide Manual，第十二版，CDSTomlin，Ed.，British Crop Protection Council，Farnham，Surrey，UK，2000。 Agricultural protection agents about these common reference is The Pesticide Manual, Twelfth Edition, CDSTomlin, Ed., British Crop Protection Council, Farnham, Surrey, UK, 2000.

用于与式I的化合物混合的优选杀虫剂和杀螨剂包括拟除虫菊酯类如氯氰菊酯、氯氟氰菊酯、百树菊酯和β-氟氯氰菊酯、高氰戊菊酯、杀灭菊酯和四溴菊酯；氨基甲酸酯类如苯硫威、灭多虫、甲氨叉威和硫双灭多威；新烟碱类(neonicotinoids)如噻虫胺、吡虫啉和噻虫啉；神经钠通道阻断剂如噁二唑虫，杀虫大环内酯如艾克敌105、阿维菌素、齐墩螨素、依马菌素；γ-氨基丁酸(GABA)拮抗剂如硫丹、ethiprole和锐劲特；杀虫脲类如氟虫脲和杀虫隆；保幼激素模拟物如噁茂醚和蚊蝇醚；拒嗪酮；和虫螨脒。 Preferred insecticides and acaricides for mixing with a compound of formula I include pyrethroids such as cypermethrin, cyhalothrin, cyfluthrin and β- cyfluthrin, esfenvalerate, killing ju esters and tralomethrin; carbamates such as thiophenol Viagra, methomyl, A fork Granville ammonia and sulfur double methomyl; neonicotinoids (neonicotinoids) as clothianidin, imidacloprid and thiacloprid; nerve sodium channel blockers such as oxadiazole insects, insecticidal macrocyclic lactone as spinosad, avermectin, abamectin, according to Ma streptozotocin; γ- aminobutyric acid (GABA) antagonists such as sulfur Dan, ethiprole and fipronil; insecticidal ureas such as flufenoxuron and insecticidal Long; juvenile hormone mimics such as ether and pyriproxyfen Mau evil; pymetrozine; and amitraz. 用于与本发明的化合物混合的优选生物试剂包括苏云金杆菌和苏云金杆菌δ-内毒素，以及天然存在的和遗传改良的病毒杀虫剂，包括杆状病毒科的成员和昆虫致病真菌。 Preferably biological agents for mixing with compounds of this invention include Bacillus thuringiensis and Bacillus thuringiensis endotoxin within δ-, as well as naturally occurring and genetically modified viral insecticides including members of Baculoviridae and entomopathogenic fungi.

在用于处理茎插的组合物中与式I的化合物混合的优选的植物生长调节剂是1H-吲哚-3-乙酸、1H-吲哚-3-丁酸和1-萘乙酸，以及它们的农业上适用的盐、酯和酰胺衍生物，如1-萘乙酰胺。 In the plant growth regulator for treating stem cutting composition is mixed with a compound of formula I is preferably 1H- indole-3-acetic acid, 1H- indole-3-butyric acid and 1-naphthaleneacetic acid, and their on agriculturally suitable salt, ester and amide derivatives, such as 1-naphthylethyl amides. 用于与式I的化合物混合的优选杀菌剂包括用作种子处理的杀菌剂如福美双、代森锰、代森锰锌和克菌丹。 Preferred fungicides for mixing with a compound of formula I include fungicide used as a seed treatment such as thiram, maneb, mancozeb and captan.

在以下实施例中，所有百分比均以重量计，并且所有配方都用常规方法制备。 In the following examples, all percentages are by weight and all formulations are prepared by a conventional method. 化合物号指索引表A中的化合物。 Compound numbers refer to compounds in Index Table A.

实施例A可湿性散剂化合物208 65.0％ Example A wettable powder Compound 208 65.0%

十二烷基酚聚乙二醇醚 2.0％木质素磺酸钠 4.0％硅铝酸钠 6.0％蒙脱石(煅烧的) 23.0％实施例B颗粒剂化合物486 10.0％硅镁土颗粒(低挥发物，0.71/0.30mm； 90.0％USSNo.25-50筛)实施例C挤压丸化合物509 25.0％无水硫酸钠 10.0％粗木质素磺酸钙 5.0％烷基萘磺酸钠 1.0％钙/镁膨润土 59.0％实施例D乳状浓缩物化合物516 20.0％油溶性磺酸盐和聚氧乙烯醚混合物 10.0％异佛乐酮 70.0％对于生长介质浸液，配方需要，通常在用水稀释后，提供在溶液中的或小到足以在液体中保持分散的颗粒的形式的式I的化合物。 Dodecylphenol polyethylene glycol ether lignin sulfonate 4.0% 2.0% 6.0% sodium aluminosilicate montmorillonite (calcined) 23.0% Example B Compound Granule 486 10.0% attapulgite granules (low volatility matter, 0.71 / 0.30mm; 90.0% USSNo.25-50 sieves) Example C extrudates Compound 509 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium / Example D Emulsion Concentrate Compound of magnesium bentonite 59.0% 516 20.0% embodiments oil soluble sulfonates and polyoxyethylene ethers 10.0% a mixture of isophorone 70.0% for growing medium drenches, the formulation needs, usually after dilution with water, to provide the solution or dispersion of small particles to form a compound of formula I sufficient to maintain in the liquid. 水分散性或水溶性散剂、颗粒剂、片剂、乳状浓缩物、含水混悬剂浓缩物等是适于生长介质水浸液的配方。 Water-soluble or water-dispersible powders, granules, tablets, emulsion concentrates, aqueous suspension concentrates and the like are suitable for growing medium flooding liquid formulation. 对于处理具有相对高的孔隙率的生长介质，如轻质土壤，或包含多孔物质的人工生长介质，如泥煤苔、珍珠岩、蛭石等，浸液是最令人满意的。 For the treatment of growth media having a relatively high porosity, such as light soils or artificial growing medium comprising porous materials such as peat moss, perlite, vermiculite, etc., immersion is the most satisfactory. 也可以将包含式I的化合物的浸液加入液体生长介质中(即水培)，这使得式I的化合物成为液体生长介质的一部分。 Infusion of compounds of formula I can also be added to the liquid containing the growth medium (i.e. hydroponics), which makes the compounds of formula I become part of the liquid growth medium. 本领域技术人员将理解，无脊椎害虫防治功效所需的浸液中的式I的化合物的量(即生物有效量)将随繁殖体的类型、式I的化合物、所需的植物保护的持续时间和范围、要防治的无脊椎害虫和环境因素而变。 Those skilled in the art will appreciate that the amount of compound type (i.e. biologically effective amount) of the desired compound of invertebrate pest control efficacy of immersion in the formula I will vary with the propagule, the Formula I, the desired duration of plant protection timing and extent of invertebrate pest to be controlled and environmental factors change. 浸液中式I的化合物的浓度通常为约0.01ppm至10000ppm，更通常为约1ppm至100ppm。 The concentration of the compound of formula I infusion is typically from about 0.01ppm to 10000ppm, more typically from about 1ppm to 100ppm. 本领域技术人员能够容易地确定所需的植食性无脊椎害虫防治水平所需的生物有效浓度。 Skilled in the art can easily determine the required phytophagous invertebrate pest control level desired biological effective concentration.

对于处理生长介质，也可以通过混合式I的化合物和干燥的散剂或颗粒剂配方而施用之。 For the treatment of growth media, can also be administered by the compound and drying the powders or granules mixed formulations of Formula I. 由于该施用方法不需要首先分散或溶解在水中，因此干燥的散剂或颗粒剂配方不需要具有高分散性或溶解性。 Because this method of application does not require first dispersing or dissolving in water, so the drying of powders or granules formulation required to have high dispersibility or solubility. 尽管在育苗箱中可以处理所有的生长介质，但在农田中由于环境和成本原因，通常仅处理繁殖体附近的泥土。 Although the nursery box can handle all of the growth medium, but in the fields due to environmental and cost reasons, usually only deal with propagules nearby soil. 为了将施用劳动和费用最小化，式I的化合物的配方施用与繁殖体种植(例如播种)同时进行最有效。 In order to minimize the cost of labor and administration, Fertilizers and propagules planted (eg sowing) compounds of Formula I are most effective at the same time. 对于沟中施用，将式I配方(最便利地为颗粒剂配方)直接施用于种植者鞋后。 For ditch administration of formula I formulation (most conveniently a granule formulation) is applied directly to the shoes after the grower. 对于T带施用，将式I配方施用在种植者鞋后和压力机轮后或通常在其前面的行的带。 For T with administration the formula I Fertilizers after growers shoes and belt after the press wheels or usually in front of the line. 本领域技术人员将理解，无脊椎害虫防治功效所需的生长介质场所中的式I的化合物的量(即生物有效量)将随繁殖体类型、式I的化合物、所需的植物保护的持续时间和范围、要防治的无脊椎害虫和环境因素而变。 Those skilled in the art will appreciate that the amount (i.e. biologically effective amount) of the desired compound of invertebrate pest control efficacy of the growth medium of properties of formula I will vary with the type of propagule, the Formula I compound, the duration required for plant protection timing and extent of invertebrate pest to be controlled and environmental factors change. 在繁殖体的生长介质场所中的式I的化合物的浓度通常为约0.0001ppm至100ppm，更通常为约0.01ppm至10ppm。 Concentration of compound in growth medium places propagules of Formula I is generally from about 0.0001ppm to 100ppm, more typically from about 0.01ppm to 10ppm. 本领域技术人员能够容易地确定所需的植食性无脊椎害虫防治水平所需的生物有效量。 Skilled in the art can easily determine the required phytophagous invertebrate pest control levels of biologically effective amount required.

可以通过在式I的化合物溶液或分散体中浸泡繁殖体而直接处理之。 Can be a solution or dispersion in a compound of Formula I directly soaking propagules of treatment. 尽管该施用方法可用于所有类型的繁殖体，但对于给发育中的植物提供无脊椎害虫防治而言，处理大种子(例如平均直径至少为3mm)比处理小种子更有效。 Although this method of administration can be used for all types of propagules, but to provide the developing plant invertebrate pest control, the handling large seeds (e.g., an average diameter of at least 3mm) is more effective than treatment of small seeds. 处理繁殖体如块茎、鳞茎、球茎、根茎、茎插和叶插，除了提供繁殖体处理以外，还能有效处理发育中的植物。 Processing propagules such as tubers, bulbs, corms, rhizomes, stems and leaves inserted plug, besides providing treatment propagules outside, but also effectively deal with the developing plants. 用于生长介质浸液的配方通常也可用于浸泡处理。 Recipe for growth media can often be used for immersion soaking. 浸泡介质包含非植物毒性液体，通常为水基的，尽管其可以包含非植物毒性量的其它溶剂如甲醇、乙醇、异丙醇、乙二醇、丙二醇、碳酸丙烯、苄醇、二元酯、丙酮、乙酸甲酯、乙酸乙酯、环己酮、二甲基亚砜和N-甲基吡咯烷酮，它们可用于提高式I的化合物的溶解性以及渗透进入繁殖体。 Soaking medium comprises a nonphytotoxic liquid, generally water-based, although other solvents which may contain non-phytotoxic amount, such as methanol, ethanol, isopropanol, ethylene glycol, propylene glycol, propylene carbonate, benzyl alcohol, dibasic esters, acetone, methyl acetate, ethyl acetate, cyclohexanone, dimethylsulfoxide and N- methylpyrrolidone, they can be used to improve the compound of formula I of solubility and penetration into the propagule. 表面活性剂可以促进繁殖体湿润和式I的化合物的渗透。 The surfactant can facilitate wetting and penetration of the compound of formula I propagules of. 本领域技术人员将理解，无脊椎害虫防治功效所需的浸泡介质中的式I的化合物的量(即生物有效量)将随繁殖体的类型、式I的化合物、所需的植物保护的持续时间和范围、要防治的无脊椎害虫和环境因素而变。 Those skilled in the art will appreciate that the amount of compound type (i.e. biologically effective amount) of the desired compound of invertebrate pest control efficacy immersion medium of formula I will vary with the propagule, the Formula I, the desired duration of plant protection timing and extent of invertebrate pest to be controlled and environmental factors change. 浸泡液中式I的化合物的浓度通常为约0.01ppm至10000ppm之间，更通常为约1ppm至100ppm。 The concentration of the compound of formula I is generally sock liquid between about 0.01ppm to 10000ppm, more typically from about 1ppm to 100ppm. 本领域技术人员能够容易地确定所需的植食性无脊椎害虫防治水平所需的生物有效浓度。 Skilled in the art can easily determine the required phytophagous invertebrate pest control level desired biological effective concentration. 浸泡时间可以为1分钟至1天甚至更长。 Soaking time may be 1-1 minutes or even longer. 实际上可以在繁殖体萌芽或发芽时将其保持在处理液中(例如直接播种前稻种的发芽)。 Actually sprout or germinate in propagules when it is held in the treatment liquid (such as direct seeding rice before germination). 由于枝条和根的形成经由种皮，因此枝条和根直接与包含式I的化合物的溶液接触。 Since the formation of shoot and root, shoot and root directly contact thus with a compound of formula I containing solution through the seed coat. 对于处理大播种作物如稻的发芽种子，处理时间为约8至48小时，如约24小时，是通常的。 For processing large germinated seeds sown crops such as rice, treatment time is about 8-48 hours, such as about 24 hours, is usual. 对于处理小种子，更短的时间最有用。 For the treatment of small seeds, the most useful shorter time.

也可以用包含生物有效量的式I的化合物的组合物涂覆繁殖体。 The composition may also be coated propagule comprising a biologically effective amount of a compound of formula I. 本发明的涂层能够通过扩散到繁殖体和周围介质中而实现式I的化合物的缓慢释放。 Slow release coating of the present invention can be obtained by diffusion into the propagule and surrounding medium is achieved formula I compound. 涂层包括通过粘结剂如甲基纤维素或阿拉伯胶的作用而粘附到繁殖体上的干粉或粉末。 Coating includes a binder such as by action of methylcellulose or acacia adhered to a dry powder or powder on the propagules. 也可由悬浮在水中的混悬剂浓缩物、水分散性粉末或乳剂，在滚筒装置中将其喷到繁殖体上，然后干燥，而制备涂层。 May also be suspended in water suspension concentrates, water-dispersible powders or emulsions, in the apparatus in which the drum is sprayed onto the propagules, followed by drying, to prepare the coating. 可以将溶解在溶剂中的式I的化合物喷在翻转的繁殖体上，然后蒸发溶剂。 Compounds may be dissolved in a solvent of formula I sprayed on the propagules inverted, and then the solvent was evaporated. 这些组合物优选包括促进涂层粘附到繁殖体的成分。 These compositions preferably comprise a coating adhered to the promotion component propagules. 该组合物还可以含有促进繁殖体湿润的表面活性剂。 The composition may also contain wetting promoting propagules surfactant. 所用溶剂必须对繁殖体无植物毒性；通常用水，但其它具低植物毒性的挥发性溶剂如甲醇、乙醇、乙酸甲酯、乙酸乙酯、丙酮等可以单独或组合使用。 The solvent must be non-phytotoxic to the propagule with; generally water, but other volatile solvents with low phytotoxicity such as methanol, ethanol, methyl acetate, ethyl acetate, acetone and the like may be used alone or in combination. 挥发性溶剂为正常沸点低于约100℃的溶剂。 Volatile solvent for the solvent normal boiling point below about 100 ℃ of. 干燥必须以不伤害繁殖体或诱导过早萌发或发芽的方式进行。 Drying must be carried out in order not to harm the propagules or induce premature germination or sprouting way.

涂层厚度从粘附粉至薄膜至丸剂层约0.5至5mm厚而变。 The thickness of the coating powder from adhering to the thin film to a bolus of about 0.5 to 5mm thick layer becomes. 本发明的繁殖体涂层可以包含多于一种粘合层，其中仅一层需包含式I的化合物。 Propagule coating of the present invention may contain more than one adhesive layer, wherein only one layer of the desired compound of formula I include. 对于小种子而言，通常丸剂是最令人满意的，因为它们提供生物有效量的式I的化合物的能力不受种子表面积的限制，并且粒化小种子也有利于种子运输和栽培工作。 For small seeds, the pellets are generally the most satisfactory, because of their ability to biologically effective amount of a compound of formula I provide unrestricted seed surface area, and the granulation is also conducive to small seeds and planting seed transport work. 由于更大尺寸和表面积，大种子和鳞茎、块茎、球茎、根茎和它们的活插条通常不进行粒化，而用粉末或薄膜涂覆代替。 Due to the larger size and surface area, large seeds and bulbs, tubers, corms, rhizomes and their viable cuttings usually not granulated, but instead coated with powders or thin films.

与本发明的式I的化合物接触的繁殖体包括种子。 Of formula I of the present invention comprises contacting a compound propagule seed. 适宜的种子包括下列植物的种子：小麦、硬质小麦、大麦、燕麦、黑麦、玉米、高梁、稻、茭白、棉花、亚麻、向日葵、大豆、四季豆、菜豆、蚕豆、豌豆、花生、苜蓿、甜菜、莴苣、油菜籽、甘蓝、芜菁、叶芥菜、黑芥、番茄、马铃薯、胡椒、茄子、烟草、黄瓜、香瓜、西瓜、南瓜、胡萝卜、百日菊、大波斯菊、菊花、松虫草、金鱼草、非洲菊、满天星、补血草、矮百合、洋桔梗、西洋蓍草、万寿菊、三色堇、凤仙花、矮牵牛花、天竺葵和紫锦苏。 Suitable seeds include seeds of the following plants: wheat, durum wheat, barley, oats, rye, corn, sorghum, rice, wild rice, cotton, flax, sunflower, soy, beans, beans, beans, peas, peanuts, alfalfa , beets, lettuce, rapeseed, kale, turnip, leaf mustard, black mustard, tomato, potato, pepper, eggplant, tobacco, cucumber, cantaloupe, watermelon, pumpkin, carrots, zinnia, cosmos, chrysanthemum, pine Cordyceps, snapdragons, gerbera, baby's breath, blood grass, dwarf lilies, lisianthus, yarrow, marigold, pansy, impatiens, petunias, geraniums and purple Jin Su. 重要的是棉花、玉米、大豆和稻的种子。 It is important cotton, corn, soybeans and rice seeds. 根据本发明与式I的化合物接触的繁殖体还包括根茎、块茎、鳞茎和球茎，或它们的活的分割部分。 According to the present invention propagule contacted with a compound of formula I also include rhizomes, tubers, bulbs and corms, or viable division section thereof. 适宜的根茎、块茎、鳞茎和球茎，或它们的活的分割部分包括下列植物的：马铃薯、甘薯、山药、洋葱、郁金香、唐菖蒲、百合、水仙、大丽花、鸢尾、藏红花、银莲花、风信子、麝香兰、小苍兰、观赏洋葱、酢浆草、红海葱、仙客来、四萼齿草，条纹红海葱、水芋百合、大岩桐和块茎状秋海棠。 Suitable rhizomes, tubers, bulbs and corms, or a live split section includes the following plants: potatoes, sweet potatoes, yams, onions, tulips, gladioli, lilies, daffodils, dahlias, iris, crocus, anemones, hyacinths musk orchid, freesia, ornamental onion, wood sorrel, Red onions, cyclamen, four calyx teeth grass, striped Red onions, calla lily, gloxinia and tuberous begonias. 重要的是马铃薯、马铃薯、甘薯、洋葱、郁金香、黄水仙、藏红花和风信子的根茎、块茎、鳞茎和球茎，或它们的活的分割部分。 It is important potato, potato, sweet potato, onion, tulips, daffodils, crocus and hyacinth roots, tubers, bulbs and corms, or a live split parts. 根据本发明与式I的化合物接触的繁殖体还包括茎插和叶插。 According to the present invention propagule contacted with a compound of formula I also include stems and leaf cutting interpolation.

与式I的化合物接触的繁殖体的一个实施方案是用包含式I的化合物、其N-氧化物或农业上适用的盐和成膜剂或粘合剂涂覆的繁殖体。 One embodiment of propagules with a compound of formula I is in contact with a compound comprising Formula I, suitable agricultural the N- oxide or a salt thereof and a film former or adhesive coated propagules. 包含生物有效量的式I的化合物、其N-氧化物或农业上适用的盐和成膜剂或粘合剂的本发明的组合物可以进一步包含有效量的至少一种其它生物活性化合物或试剂。 Comprising a biologically effective amount of a compound of formula I, N- oxides or composition thereof agriculturally suitable salt thereof and a film former or adhesive of the present invention may further comprise an effective amount of at least one additional biologically active compound or agent . 重要的组合物包含(除式I组分和成膜剂或粘合剂以外)下组的杀节肢动物剂：拟除虫菊酯类、氨基甲酸酯类、新烟碱类、神经元钠通道阻断剂类、杀虫大环内酯类，γ-氨基丁酸(GABA)拮抗剂类、杀虫脲类和保幼激素模拟物类。 Important compositions comprise (in addition to Formula I component and the film former or adhesive other than) the group arthropodicides: pyrethroids, carbamates, neonicotinoids, neuronal sodium channel blockers agents, insecticidal macrolides, γ- aminobutyric acid (GABA) antagonists, insecticidal ureas and juvenile hormone mimics class. 同样重要的是组合物包含(除式I组分和成膜剂或粘合剂以外)至少一种选自下组的其它生物活性化合物或试剂阿维菌素、乙酰甲胺磷、吡虫清、amidoflument(S-1955)、齐墩螨素、艾扎丁、谷硫磷、氟氯菊酯、binfenazate、噻嗪酮、呋喃丹、氟唑虫清、定虫隆、毒死蜱、甲基毒死蜱、环虫酰肼、噻虫胺、百树菊酯、β-氟氯氰菊酯、氯氟氰菊酯、λ-氯氟氰菊酯、氯氰菊酯、灭蝇胺、溴氰菊酯、杀螨硫隆、二嗪农、氟脲杀、乐果、噁茂醚、依马菌素、硫丹、高氰戊菊酯、ethiprole、苯硫威、双氧威、甲氰菊酯、唑螨酯、杀灭菊酯、锐劲特、flonicamid、氟氰戊菊酯、氟胺氰菊酯、flufenerim(UR-50701)、氟虫脲、地虫磷、特丁苯酰肼、氟铃脲、吡虫啉、噁二唑虫、丙胺磷、氟丙氧脲、马拉硫磷、蜗牛敌、甲胺磷、杀扑磷、灭多虫、蒙五一五、甲氧滴滴涕、久效磷、甲氧苯酰肼、硝虫噻嗪、双苯氟脲、noviflumuron(XDE-007)、甲氨叉威、对硫磷、甲基对硫磷、氯菊酯、甲拌磷、伏杀磷、亚胺硫磷、磷胺、抗蚜威、丙溴磷、拒嗪酮、pyridalyl、蚊蝇醚、鱼藤酮、艾克敌105、spiromesifin(BSN2060)、乙丙硫磷、双苯酰肼、伏虫隆、七氟菊酯、特丁磷、杀虫畏、噻虫啉、噻虫嗪、硫双灭多威、杀虫双、四溴菊酯、敌百虫和杀虫隆、涕灭威、甲氨叉威、克线磷、虫螨脒、灭螨猛、乙酯杀螨醇、三环锡、开乐散、除螨灵、特苯噁唑、喹螨醚、杀螨锡、甲氰菊酯、唑螨酯、噻螨酮、克螨特、哒螨酮、吡螨胺；和生物试剂如包括苏云金杆菌a和苏云金杆菌k在内的苏云金杆菌，苏云金杆菌δ-内毒素、杆状病毒，以及昆虫致病细菌、病毒和真菌。 Equally important is the composition comprising other biologically active compounds or agents avermectin (except Formula I component and the film former or adhesive outside) at least one selected from the group, acephate, acetamiprid , amidoflument (S-1955), abamectin, Yi Zhading, azinphos-methyl, bifenthrin, binfenazate, buprofezin, carbofuran, chlorfenapyr, Chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, Central tebufenozide, clothianidin, cyfluthrin, β- cyfluthrin, cyhalothrin, λ- cyhalothrin, cypermethrin, cyromazine, deltamethrin, mites sulfur Long, two Diazinon, fluorouracil kill, dimethoate, evil Mao ether, according to Ma streptozotocin, endosulfan, esfenvalerate, ethiprole, benzene, sulfur Viagra, fenoxycarb, fenpropathrin, Fenpyroximate kill Ju ester, Fipronil, flonicamid, flucythrinate, fluvalinate, flufenerim (UR-50701), flufenoxuron, FONOFOS, halofenozide, hexaflumuron, imidacloprid, oxadiazole insects, propylamine phosphorus, fluorine propoxyphene urea, malathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, monocrotophos, methicillin hydrazide, nitrate insect thiazide, novaluron, noviflumuron (XDE-007), A fork ammonia Viagra, parathion, methyl parathion, permethrin, phorate, phosalone, phosmet, phosphamidon , pirimicarb, profenofos, pymetrozine, pyridalyl, pyriproxyfen, rotenone, spinosad 105, spiromesifin (BSN2060), ethylene-propylene parathion, tebufenozide, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, thiacloprid, thiamethoxam, thiodicarb methomyl, Bisultap, tralomethrin, trichlorfon and insecticidal Long, aldicarb, A fork Granville ammonia, g-line phosphorus, amitraz, Chinomethionate, mites, ethyl alcohol, cyhexatin, dicofol, mites and spirit, especially benzene, oxazole, Fenazaquin, mites tin, fenpropathrin, Fenpyroximate, hexythiazox, propargite, pyridaben, tebufenpyrad; and biological agents such as Bacillus thuringiensis including a Bacillus thuringiensis and Bacillus thuringiensis including k, within δ- endotoxin of Bacillus thuringiensis, baculovirus and insect pathogenic bacteria , viruses and fungi. 同样重要的组合物包含(除式I组分和成膜剂或粘合剂以外)至少一种选自下组的杀菌剂的其它生物活性化合物或试剂：噻二唑素、腈嘧菌酯、苯菌灵、灭瘟素、波尔多液(碱式硫酸铜)、糠菌唑、氯环丙酰胺、敌菌丹、克菌丹、多菌灵、地茂散、百菌清、王铜、铜盐、cyflufenamid、清菌脲、环唑醇、环丙嘧啶、(S)-3，5-二氯-N-(3-氯-1-乙基-1-甲基-2-氧丙基)-4-甲基苯甲酰胺(RH7281)、双氯氰菌胺(S-2900)、哒菌清、氯硝胺、噁咪唑、(S)-3，5-二氢-5-甲基-2-(甲硫基)-5-苯基-3-(苯氨基)-4H-咪唑-4-酮(RP 407213)、烯酰吗啉、dimoxystrobin、烯唑醇、烯唑醇-M、多果定、克瘟散、氧唑菌、噁唑酮菌、咪唑菌酮、异嘧菌醇、腈苯唑、fencaramid(SZX0722)、拌种咯、苯锈啶、丁苯吗啉、薯瘟锡、毒菌锡、氟啶胺、氟噁菌、氟联苯菌(RPA 403397)、flumorf/flumorlin(SYP-L190)、fluoxastrobin(HEC5725)、喹唑菌酮、氟硅唑、氟酰胺、粉唑醇、灭菌丹、藻菌磷、呋氨丙灵、呋吡唑灵(S-82658)、己唑醇、环戊唑醇、异稻瘟净、异丙定、稻瘟灵、春雷霉素、亚胺菌、代森锰锌、代森锰、mefenxam、丙氧灭绣胺、甲霜灵、环戊唑菌、叉氨苯酰胺(SSF-126)、metrafenone(AC375839)、腈菌唑、田安甲胂铁(甲基胂酸铁)、nicobifen(BAS 510)、orysastrobin、噁霜灵、戊菌唑、戊菌隆、噻菌灵、丙氯灵、百维灵、丙环唑、proquinazid(DPX-KQ926)、prothioconazole(JAU6476)、啶斑肟、pyraclostrobin、二甲嘧菌胺、咯喹酮、喹氧灵、螺噁茂胺、硫、戊唑醇、氟醚唑、涕必灵、溴氟唑菌、甲基托布津、福美双、tiadinil、三唑酮、唑菌醇、三环唑、肟菌酯、戊叉唑菌、有效霉素和烯菌酮(尤其是其中至少一种其它生物活性的化合物或试剂是选自福美双、代森锰、代森锰锌和克菌丹的杀菌剂的组合物)。 Equally important, the composition comprises at least one selected from the group of fungicides (except Formula I component and the film former or adhesive other than) the other biologically active compounds or agents: acibenzolar, azoxystrobin, benomyl, blasticidin, Bordeaux mixture (basic copper sulfate), bromuconazole, chlorine cyproterone amide, captafol, captan, carbendazim, to Mao San, chlorothalonil, king of copper, copper salts, cyflufenamid, clear iprodione, cyproconazole, cyclopropylmethyl pyrimidine, (S) -3,5- dichloro -N- (3- chloro-1-ethyl-1-methyl-2-oxopropyl) -4-methyl-benzamide (RH7281), double cyanuric bacteria amine (S-2900), Da Qing bacteria, chlorine Nitramine, oxpoconazole, (S) -3,5- dihydro-5-methyl - 2- (methylthio) -5-phenyl-3- (phenylamino) -4H--imidazol-4-one (RP 407213), dimethomorph, dimoxystrobin, diniconazole, diniconazole -M, more dodine, g blast scattered, epoxiconazole, oxazolone bacteria, fenamidone, iso triarimol, fenbuconazole, fencaramid (SZX0722), fenpiclonil, fenpropidin, fenpropimorph, Ralstonia solanacearum tin , toadstool tin, Fluazinam, fluorine bad bacteria, flurbiprofen bacteria (RPA 403397), flumorf / flumorlin (SYP-L190), fluoxastrobin (HEC5725), quinazolinone cycloheximide, Flusilazole, Flutolanil, pink azole alcohol, folpet, algae bacteria phosphorus, metalaxyl furosemide, furosemide pyrazole Spirit (S-82658), Hexaconazole, cyclopentyl Hexaconazole, Iprobenfos, isopropyl set, Isoprothiolane, Kasugamycin imine bacteria, mancozeb, maneb, mefenxam, propoxyphene off embroidered amine, metalaxyl, metconazole, fork benzamide (SSF-126), metrafenone (AC375839), myclobutanil, Tian A arsine iron (methyl arsenic acid iron), nicobifen (BAS 510), orysastrobin, oxadixyl, penconazole, pencycuron, thiabendazole, prochloraz, one hundred spiritual dimension, propiconazole, proquinazid ( DPX-KQ926), prothioconazole (JAU6476), pyrifenox, pyraclostrobin, dimethyl mepanipyrim, pyroquilon, quinoxyfen, snails dioxolyl amines, sulfur, tebuconazole, fluorine difenoconazole, thiabendazole, bromine fluorine yl bacteria, thiophanate-methyl, thiram, tiadinil, triadimefon, oxazole bacteria alcohol, tricyclazole, trifloxystrobin, pentyl fork oxazole bacteria, validamycin and alkenyl cycloheximide (especially wherein the at least one other biologically active compound or agent is selected from thiram, composition maneb, mancozeb and captan fungicide).

通常本发明的繁殖体涂层包含式I的化合物、成膜剂或粘合剂。 Typically propagule coating of the invention comprises compounds of formula I, a film former or adhesive. 涂层可以进一步包含配方助剂如分散剂、表面活性剂、载体和任选的消泡剂和染料。 The coating may further comprise formulation aids such as a dispersant, a surfactant, a carrier and optionally antifoam and dye. 本领域技术人员将理解，无脊椎害虫所需功效所需的涂层中的式I的化合物的量(即生物有效量)将随繁殖体的类型、式I的化合物、所需的植物保护的持续时间和范围、要防治的无脊椎害虫和环境因素而变。 Those skilled in the art will appreciate that the amount (i.e. biologically effective amount) of the desired compound invertebrate pest desired effect in the coating of formula I will vary with the type of propagule, compounds of formula I, required for plant protection the duration and scope of invertebrate pest to be controlled and environmental factors change. 涂层需要不抑制繁殖体的发芽或萌芽，并应当在目标无脊椎害虫生命周期的导致植物损伤阶段期间始终有效减少植物损伤。 Coating need not inhibit germination or sprouting propagules and should target invertebrate pest's life cycle is always effective in reducing plant damage cause plant damage during the stage. 包含足够的式I的化合物的涂层可以提供无脊椎害虫防治保护达约120天或者甚至更久。 Coating compounds contain enough formula I can provide invertebrate pest control protection for about 120 days, or even longer. 通常式I的化合物的量为繁殖体重量的约0.001-50％，对于种子而言，更通常为种子重量的约0.01-50％，对大种子而言，最通常为种子重量的约0.1-10％。 Amount of the compound of formula I is generally from about 0.001 to 50% by weight of the propagule, for seeds, the more typically from about 0.01 to 50% of the seed weight, in terms of large seeds, seed weight and most typically from about 0.1 to 10%. 然而，更高量，达约100％或更高是有利的，特别是对于延长无脊椎害虫防治保护用的粒化小种子而言。 However, higher amounts, up to about 100% or more is advantageous, especially for extended invertebrate pest control protection of small seeds, granulated. 对于繁殖体如根茎、块茎、鳞茎和球茎和它们的活插条，以及茎插和叶插而言，通常式I的化合物的量为繁殖体重量的约0.001-5％，更高的百分比用于更小的繁殖体。 For propagules such as the amount of rhizomes, tubers, bulbs and corms, and their live cuttings, and stem and leaf cutting interpolation, the compound of formula I generally ranges from about 0.001 to 5% by weight of the propagule, a higher percentage in smaller propagules. 本领域技术人员能够容易地确定所需的植食性无脊椎害虫防治水平所需的生物有效量。 Skilled in the art can easily determine the required phytophagous invertebrate pest control levels of biologically effective amount required.

繁殖体涂层的成膜剂或粘合剂组分优选由粘合剂聚合物组成，所述粘合剂聚合物可以是天然或合成的，并且对要涂覆的繁殖体无植物毒性作用。 Propagule coating film former or binder component preferably consists of a binder polymer, the binder polymer may be natural or synthetic, and the propagule to be coated on the non-phytotoxic effect. 成膜剂或粘合剂可以选自乙酸乙烯酯、聚乙酸乙烯酯共聚物、水解的聚乙酸乙烯酯、聚乙烯吡咯烷酮-乙酸乙烯酯共聚物、聚乙烯醇、聚乙烯醇共聚物、聚乙烯基甲基醚、聚乙烯基甲基醚-马来酸酐共聚物、蜡、胶乳聚合物、包括乙基纤维素和甲基纤维素、羟甲基纤维素、羟丙基纤维素、羟甲基丙基纤维素的纤维素、聚乙烯吡咯烷酮、藻酸盐、糊精、麦芽糖糊精、多糖、脂肪、油、蛋白质、刺梧桐树胶、加尔胶、黄蓍胶、多糖胶、胶浆、阿拉伯胶、虫胶、偏二氯乙烯聚合物和共聚物、大豆基蛋白聚合物和共聚物、木质素磺酸盐、丙烯酸共聚物、淀粉、聚丙烯酸乙烯酯、玉米醇溶蛋白、明胶、羧甲基纤维素、脱乙酰壳多糖、聚环氧乙烷、丙烯酰亚胺聚合物和共聚物、聚丙烯酸羟乙酯、甲基丙烯酰亚胺单体、藻酸盐、乙基纤维素、聚氯丁二烯和糖浆或它们的混合物。 Film formers or binders may be selected from vinyl acetate, polyvinyl acetate copolymers, hydrolyzed polyvinyl acetate, polyvinyl pyrrolidone - vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers, polyvinyl methyl ether, polyvinyl methyl ether - maleic anhydride copolymer, waxes, latex polymers, including ethyl cellulose and methyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxymethyl propyl cellulose, polyvinylpyrrolidone, alginates, dextrin, maltodextrin, polysaccharides, fats, oils, proteins, karaya gum, gum Calcutta, tragacanth, gum, glue, gum arabic , shellac, vinylidene chloride polymers and copolymers, soybean-based protein polymers and copolymers, lignosulfonates, acrylic copolymers, starches, polyacrylic acid vinyl esters, zein, gelatin, carboxymethyl cellulose, chitosan, polyethylene oxide, acrylimide polymers and copolymers, polyacrylic acid, hydroxyethyl acrylate, methacrylic acid imide monomers, alginate, ethylcellulose, polychloroprene butadiene and syrups or mixtures thereof. 优选的成膜剂和粘合剂包括乙酸乙烯酯的聚合物和共聚物、聚乙烯吡咯烷酮-乙酸乙烯酯共聚物和水溶性蜡。 Preferred film formers and binders include polymers and copolymers of vinyl acetate, polyvinyl pyrrolidone - vinyl acetate copolymer and water-soluble waxes. 特别优选的是聚乙烯吡咯烷酮-乙酸乙烯酯共聚物和水溶性蜡。 Especially preferred are polyvinyl pyrrolidone - vinyl acetate copolymer and water-soluble waxes. 上述聚合物包括那些本领域已知的以及例如AgrimerVA 6和LicowaxKST。 Above polymers include those known in the art and, for example AgrimerVA 6 and LicowaxKST. 配方中的成膜剂或粘合剂的量通常为繁殖体重量的约0.001-100％。 The amount of the binder formulations or film-forming agent is generally from about 0.001 to 100% by weight of the propagule. 对于大种子而言，成膜剂或粘合剂的量通常为种子重量的约0.05-5％；对于小种子而言，该量通常为约1-100％，但在粒化中可高于种子重量的100％。 For large seeds, the amount of film former or adhesive is generally from about 0.05 to 5% of the seed weight; for small seeds, the amount is usually about 1 to 100%, but may be higher than in the granulation 100% of the weight of the seed. 对于其它繁殖体而言，成膜剂或粘合剂的量通常为繁殖体重量的约0.001-2％。 For other propagules, the amount of film former or adhesive is usually about 0.001 to 2% by weight of the propagule.

已知为配方助剂的物质也可以用于本发明的用于无脊椎害虫防治的繁殖体处理涂层中，并且这是本领域技术人员所熟知的。 A substance known as formulation aids may also be used in the present invention is used in propagule invertebrate pest control treatment coating, and it is to those skilled in the art. 配方助剂有助于繁殖体处理的产生或加工，包括但不限于分散剂、表面活性剂、载体、消泡剂和染料。 Formulation aids helps produce propagules treatment or processing, including but not limited to dispersants, surfactants, carriers, antifoams and dyes. 有用的分散剂可以包括高水溶性阴离子表面活性剂，如BorresperseTMCA、MorwetD425等。 Useful dispersants can include highly water-soluble anionic surfactants, such as BorresperseTMCA, MorwetD425 like. 有用的表面活性剂可以包括高水溶性非离子表面活性剂，如PluronicF108、Brij78等。 Useful surfactants can include highly water-soluble nonionic surfactants, such as PluronicF108, Brij78 like. 有用的载体可以包括液体如水和油，它们是水溶性的，如醇。 Useful carriers can include liquids such as water and oils, which are water soluble, such as alcohols. 有用的载体还可以包括填料如木粉、粘土、活性炭、硅藻土、细粒无机固体、碳酸钙等。 Useful carriers can also include fillers such as wood flour, clay, activated carbon, diatomaceous earth, fine particles of inorganic solids, calcium carbonate and the like. 可以使用的粘土和无机固体包括钙膨润土、高岭土、陶土、滑石、珍珠岩、云母、蛭石、二氧化硅、石英粉、蒙脱石及它们的混合物。 Clay and inorganic solids which may be used include calcium bentonite, kaolin, clay, talc, perlite, mica, vermiculite, silicas, quartz powder, montmorillonite and mixtures thereof. 消泡剂可以包括包含聚有机硅氧烷如Rhodorsil416的水分散性液体。 Antifoaming agents may comprise water-dispersible polyorganosiloxane containing liquids such as Rhodorsil416 of. 染料可以包括水分散性液体着色剂组合物如Pro-lzedColorant Red。 Dyes can include water dispersible liquid colorant compositions such as Pro-lzedColorant Red. 本领域技术人员将理解，这是非穷尽的助剂列举，并且根据要涂覆的繁殖体和用于涂覆的式I的化合物，可以使用经认可的其它物质。 Those skilled in the art will appreciate that this is a non-exhaustive lists of additives, and the compound according to propagule to be coated and a coating of the formula I may be used other materials approved. 适宜的配方助剂的实例包括本文和由MC PublishingCompany出版的McCutcheon's 2001，Volume 2：Functional Materials，中所列的。 Suitable examples of formulation aids include herein and published by MC PublishingCompany McCutcheon's 2001, Volume 2: Functional Materials, listed. 配方助剂的用量可以变化，但通常该组分的重量将为繁殖体重量的约0.001-10000％，100％以上的百分比主要用于粒化小种子。 The amount of formulation aids may vary, but generally the weight of the granulated small seeds that component will be about 0.001-10000 propagules wt%, the percentage of 100% is mainly used. 对于未粒化的种子，配方助剂的量通常为种子重量的约0.01-45％，通常为种子重量的约0.1-15％。 For non-granulated seed, the amount of formulation aids is generally from about 0.01-45% of the seed weight, typically from about 0.1 to 15% weight of the seed. 对于除种子以外的繁殖体，配方助剂的量通常为繁殖体重量的约0.001-10％。 For propagules other than seeds, the amount of formulation aids generally is about 0.001 to 10% by weight of the propagule.

施用种子涂层的常规方法可以用于进行本发明的涂覆。 Applying a conventional method may be used for seed coating coating of the invention. 细粉或粉末的可以如下施用：用包含式I的化合物和粘合剂的配方翻转繁殖体，使得细粉或粉末粘附于该繁殖体，并且在包装或运输期间不脱落。 Fine powder or powder may be administered as follows: The formulation comprises a compound of formula I and the binder flip propagules such fine powder or powder adhering to the propagule and not fall off during packaging or transportation. 细粉或粉末也可以如下施用：将细粉或粉末直接加入繁殖体滚筒床，随后将载体液体喷到种子上并干燥。 Fine powder or powder may also be administered as follows: The powder or powder directly into the bed of propagules drum, the carrier liquid is then sprayed onto the seed and drying. 包含式I的化合物的细粉和粉末也可以如下施用：用任选地包含粘合剂溶剂，如水处理(例如浸渍)至少一部分繁殖体，并将经处理的部分浸入所提供的干燥细粉或粉末中。 Fine powder and powder of a compound comprising the formula I can also be administered as follows: optionally contain a binder with a solvent, such as water treatment (e.g., dipping), at least a portion of propagules, and the dried powder of the partially immersed in a treatment or provided powder. 该方法用于涂覆茎插特别有用。 This method is particularly useful for coating stem insertion. 也可以将繁殖体浸入包含式I可湿性粉、溶液、悬乳剂、乳状浓缩物和在水中的乳剂的配方中，然后干燥或直接种植在生长介质中。 Propagule can also comprise Formula I immersed wettable powders, solutions, suspensions, emulsions, emulsion concentrates and emulsions in water formulation, and then dried or directly planted in the growth medium. 繁殖体如鳞茎、块茎、球茎、根茎通常仅需要单一涂层来提供生物有效量的式I的化合物。 Propagules such as bulbs, tubers, corms, rhizomes typically need only a single coating layer to provide a biologically effective amount of a compound of formula I.

也可以通过直接将悬浮液浓缩物喷在繁殖体滚筒床中，然后干燥繁殖体而涂覆繁殖体。 Can also be directly sprayed in the suspension concentrate propagules roller bed of propagules and then drying the coating propagules. 或者，可以将其它配方类型，如可湿性粉末、溶液剂、悬乳剂、乳状浓缩物和在水中的乳剂喷到繁殖体上。 Alternatively, the other formulation types, such as wettable powders, solutions, suspensions emulsions, emulsion concentrates and water in the emulsion is sprayed onto the propagules. 该方法对于将膜施用于种子而言特别有用。 The method is particularly useful for the purposes of the film is applied to the seed. 本领域技术人员可利用多种涂覆机械和方法。 Skilled in the art can utilize a variety of mechanical and coating methods. 适宜的方法包括在P.Kosters等，Seed Treatment：Progress and Prospects，1994 BCPC Monograph No.57和其中列出的参考文献中所列的。 Suitable methods include P.Kosters etc., Seed Treatment: Progress and Prospects, 1994 BCPC Monograph No.57 and wherein the list of references listed. 三种熟知的技术包括使用滚筒涂覆器、流化床技术和喷动床。 Three kinds of well-known techniques, including the use of roller coating, fluidized bed technology and spouted bed. 在涂覆前可对繁殖体如种子预先按大小分级。 Before the coating can be pre-graded by size of propagules such as seeds. 涂覆后，干燥繁殖体，随后任选地通过转移至分级机而根据大小分级。 After coating, drying the propagules, optionally followed by transfer to the classifier according to size fractionation. 这些机械是本领域已知的，例如用于工业中按大小分级玉米种子的典型机械。 These machines are known in the art, for example for the industry by size classification of typical mechanical corn seed.

对于涂覆种子，种子和涂覆物质在任何多种常规种子涂覆装置中混合。 For coating seed, the seed and coating material are mixed in any variety of conventional seed coating apparatus. 滚动速率和涂层施用取决于种子。 Rolling and coating application rate depends on the seed. 对于大的长方形种子如棉花的种子，令人满意的种子涂覆装置包括具有提升轮叶的旋转型盘，提升轮叶转动的rpm足以保持种子滚动，促进均一覆盖。 For large oblong seeds such as seed cotton, a satisfactory seed coating apparatus comprises a lifting vane rotary disc, rotating the lifting vanes rpm is sufficient to maintain the seed roll to promote uniform coverage. 对于以液体施用的种子涂覆配方，种子涂层必须施用足够的时间来干燥，以使种子结块最小化。 For liquid coating formulations administered seeds, seed coating must be applied sufficient time to dry, in order to minimize agglomeration seeds. 使用强迫通风或加热强迫通风可以提高施用速度。 The use of forced ventilation or forced air heating can increase application speed. 本领域技术人员还将认识到，该方法可以是分批法或连续法。 Those skilled in the art will also appreciate that the method may be a batch process or a continuous process. 如名称所暗示的，连续法让种子在整个产物运转期间连续流动。 As the name implies, a continuous process so that the seeds during the entire operation of a continuous flow of product. 新种子在稳定流中进入盘中，以替代从盘中流出的经涂覆的种子。 New seed into the dish steady stream to replace coated seeds outflow from the disk.

本发明的种子涂覆方法不限于薄膜涂覆，也可以包括种子粒化。 Seed coating methods of the present invention is not limited to the thin film coating may also include seed granulation. 粒化方法通常提高种子重量2-4倍，也可以用于改善种子的形状，以用于播种机中。 Granulation method is usually 2-4 times increase seed weight, may also be used to improve the shape of the seed, for use in the planter. 粒化组合物通常含有固体稀释剂，其通常为不溶性颗粒物质，如粘土、重质碳酸钙、粉末二氧化硅等，以提供除粘合剂以外的大部分，所述粘合剂如人造聚合物(例如聚乙烯醇、水解聚乙酸乙烯酯、聚乙烯基甲基醚、聚乙烯基甲基醚-马来酸酐共聚物，和聚乙烯吡咯烷酮)或天然聚合物(例如藻酸盐、刺梧桐树胶、加尔胶、黄蓍胶、多糖胶、粘胶)。 Granulated compositions generally contain a solid diluent, it is generally insoluble particulate matter, such as clay, heavy calcium carbonate, silica powder, etc., to provide most, in addition to the adhesive than the adhesive such as artificial polymerization (e.g. polyvinyl alcohol, hydrolyzed polyvinyl acetate, polyvinyl methyl ether, polyvinyl methyl ether - maleic anhydride copolymers, and polyvinyl pyrrolidone) or natural polymers (e.g., alginate, karaya gums, Gard gum, tragacanth gum, gum, glue). 在构建足够多的层后，干燥涂层并进行丸粒分级。 After building a sufficient number of layers, and the coating was dried pellets graded. 生产丸剂的方法描述于Agrow，The Seed Treatment Market，Chapter 3，PJB Publiction Ltd.，1994。 The method of producing pellets is described in Agrow, The Seed Treatment Market, Chapter 3, PJB Publiction Ltd., 1994.

适于用式I的化合物涂覆繁殖体的组合物组分和方法的进一步描述见美国专利4,443,637、5,494,709、5,527,760、5,834,006、5,849,320、5,876,739、6,156,699、6,199,318、6,202,346和6,230,438，以及欧洲专利公开EP-1,078,563-A1。 Further description of composition components and methods of using the compounds of formula I suitable for coating propagules see U.S. Patent 4,443,637,5,494,709,5,527,760,5,834,006,5,849,320,5,876,739,6,156,699,6,199,318,6,202,346 and 6,230,438, and European Patent Publication EP- 1,078,563-A1.

以下实施例EH说明涂覆种子的方法。 EH following examples illustrate methods for seed coating. 化合物号指索引表A中的化合物。 Compound numbers refer to compounds in Index Table A.

实施例E包含化合物208的组合物涂覆的棉籽批的制备步骤1：包含化合物208的易流动的悬浮液的制备制备含有表7中所列成分的易流动的悬浮液表7易流动的悬浮液中成分的量 Preparation of cottonseed batches Step Example E composition comprising a compound coating 208. 1: Preparation of a suspension table flowable suspension containing compound 208 in Table 7 containing the ingredients listed in pourable flowable suspension 7 the amount of liquid component

AgrimerVA 6是软化点为106℃的高水溶性的成膜粘合剂，其包含聚乙烯吡咯烷酮-乙酸乙烯酯共聚物，由International Specialty Product(ISP)销售。 AgrimerVA 6 is a high softening point of 106 ℃ water soluble film-forming binder comprising polyvinyl pyrrolidone - vinyl acetate copolymer, from International Specialty Product (ISP) sales. LicowaxKST是液滴形成(drop forming)点为59℃的高水溶性的成膜粘合剂，其包含褐煤蜡酸、聚乙二醇酯，由Clariant销售。 LicowaxKST is droplet formation (drop forming) the high point of the water-soluble film-forming binder 59 ℃ comprising montan wax acid, polyethylene glycol esters, sold by Clariant. BorresperseTMCA是软化点为132℃的高水溶性阴离子分散剂，其包含去糖木质素磺酸钙，由Borregaard LignoTech销售。 BorresperseTMCA a softening point of a highly water soluble anionic dispersant 132 ℃ comprising calcium lignosulfonate to sugar, sold by Borregaard LignoTech. PluronicF-108是熔化点为57℃的高水溶性非离子分散剂，其包含聚氧丙烯-聚氧乙烯嵌段共聚物，由BSAF销售。 PluronicF-108 is a high melting point of water-soluble nonionic dispersant 57 ℃ comprising polyoxypropylene - polyoxyethylene block copolymer, sold by BSAF. Brij78是倾点为38℃的高水溶性非离子分散剂，其包含十八烷醇(POE 20)，由Uniqema销售。 Brij78 the pour point of a highly water soluble nonionic dispersant 38 ℃ comprising stearyl alcohol (POE 20), sold by Uniqema. Rhodorsil416是水分散性液体消泡剂，其包含聚硅氧烷和乳化剂，由Rhodia销售。 Rhodorsil416 is a water-dispersible liquid antifoam, comprising a polysiloxane and an emulsifier, sold by Rhodia. Pro-lzedColorant Red是水分散性液体着色剂组合物，其包含红色着色剂、高岭土和非离子表面活性剂，由Gustafson销售。 Pro-lzedColorant Red is a water-dispersible liquid colorant composition comprising a red colorant, kaolin clay and a nonionic surfactant, marketed by Gustafson.

如下制备悬浮液载体(253.20g)：首先将Brij78(6.00g)溶解在温水(210.48g)中，随后剧烈混合在AgrimerVA 6(15.00g)、LicowaxKST(15.00g)、BorresperseTMCA(3.00g)、PluronicF-108(3.00g)、Brij78(6.00g)、Rhodorsil416(0.6g)和Pro-lzedColorant Red(0.12g)中。 Suspension vehicle were prepared as follows (253.20g): First Brij78 (6.00g) was dissolved in warm water (210.48g), followed by vigorously mixing in AgrimerVA 6 (15.00g), LicowaxKST (15.00g), BorresperseTMCA (3.00g), PluronicF-108 (3.00g), Brij78 (6.00g), Rhodorsil416 (0.6g) and Pro-lzedColorant Red in (0.12g). 将化合物208(15.6g)加入烧杯中，随后加入部分经完全混合的悬浮液载体(84.4g)，用刮勺将化合物208混入该悬浮液载体中。 Compound 208 (15.6g) added to the beaker, followed by the addition of part of the thoroughly mixed suspension carrier (84.4g), with a spatula Compound 208 mixed into the suspension carrier. 然后进一步用具有10mm振荡器探棒(generator probe)的Polytron高速旋转定片分散器(由Brinkman Instruments Inc.，Cantiague Rd.，Westbury，NY11590 USA销售)将混合物进一步均化，使化合物208聚集体碎裂。 Then further homogenized with a Polytron oscillator having a 10mm probe (generator probe) piece of high-speed rotation disperser (manufactured by Brinkman Instruments Inc., Cantiague Rd., Westbury, NY11590 USA sales) and the mixture was further homogenized, crushed aggregate Compound 208 crack.

然后将所得浆料转移入运转着的磨中，该磨装有80％容量的0.5-mm，单一大小的(mono-sized)高密度陶瓷研磨介质，通过使冷的33％乙二醇水溶液通过磨室的冷却套管而将其冷却。 The resulting slurry is then transferred into the operation of the mill, the mill is equipped with 80% of the capacity of the 0.5-mm, single sized (mono-sized) high density ceramic grinding media, by cold 33% ethylene glycol aqueous solution by grinding chamber cooling jacket and allowed to cool. 在搅拌器在4300rpm旋转下，使浆料再循环通过磨室13分钟。 Under the agitator rotating at 4300rpm, the slurry is recirculated through the milling chamber 13 minutes. 然后从磨进料漏斗移动循环管端至收集瓶，得到最终的粉红色高度可倾注的易流动的悬浮液(89.5g)。 And from the mill feed funnel moving circulation pipe end to collection bottle to obtain the final pink highly pourable flowable suspension (89.5g).

用激光衍射仪分析悬浮液中经微粉化(磨制)的颗粒的直径。 Analysis diameter suspension micronized (milled) particles with a laser diffractometer. 使用两次测量的平均值，算术平均粒径为2.03μm，90％的颗粒粒径小于5.21μm，10％的颗粒粒径小于0.30μm，中值粒径为1.0μm。 Using the average of two measurements, the arithmetic average particle diameter of 2.03μm, 90% of the particle size of less than 5.21μm, 10% particle size of less than 0.30μm, the median particle diameter of 1.0μm.

步骤2：用包含化合物208的组合物涂覆棉籽将棉籽(Stoneville 4793 RR，122.5g)加入含有两个相反的提升叶片的不锈钢罐(12cm id，11cm深)中，所述提升叶片随罐转动而提升种子。 Step 2: Using a composition comprising Compound 208 Cottonseed The coated cottonseed (Stoneville 4793 RR, 122.5g) was added containing two opposite lifting blades of stainless steel tanks (12cm id, 11cm depth), the lifting blades rotating with the tank and enhance seed. 罐的方向与水平成40-45°角，并以640rpm机械旋转，这在罐内导致良好的混合和翻转运动。 Direction and level tank into a 40-45 ° angle, and 640rpm mechanical rotation, which leads to good mixing and turning motions in the tank.

将步骤1中制备的易流动的悬浮液直接喷到种子的翻转床上，气压供给为10-11psi(69-76kPa)，以产生细小微滴。 The flowable suspension prepared in Step 1 is directly sprayed onto the seed bed is reversed, the air pressure supplied to 10-11psi (69-76kPa), to produce fine droplets. 通过测量容器的重量可以测定喷在种子上的易流动的悬浮液的量。 Can be determined amount of flowable suspension sprayed on the seeds by weight of the measurement reservoir. 随着种子翻转，将手控雾化器指向罐的内部，以直接喷在种子翻转床的中心。 With seed flip manual will point to the internal tank atomizer to spray directly in the center of the seed bed flipped. 喷雾继续到种子表面发粘，导致种子结块。 Continue to spray the seed surface sticky, causing seed caking. 然后关闭雾化器，通过在室温下从装备以控制罐内气流方向的喷嘴将低压气体吹到种子上而快速干燥种子涂层。 Then close the nebulizer, via at room temperature from tank equipped with an air flow direction control nozzle low pressure gas is blown onto the seed and rapid drying seed coating. 翻转的种子的声音提高提供可听到的信号，即种子涂层充分干燥。 Flip seeds provide improved sound audible signal that the seed coating was sufficiently dried. 然后关闭干燥气流，重新开始用手控雾化器喷雾。 Then close the drying gas, restarted manually controlled atomizer spray. 重复喷雾和干燥循环，直到已将所需量的易流动的悬浮液施用于种子上。 Spray and dry cycle was repeated until the desired amount has been flowable suspension applied to the seed. 然后通过暴露于低环境空气流中60小时而完成种子涂层的干燥。 Then by exposure to a low flow of ambient air for 60 hours to complete the drying of the seed coating.

通过在珠磨(bead mill)中将每粒种子浸软，然后加入乙腈萃取溶剂而测定施加于来自每批的十粒种子的化合物208的重量。 By bead mill (bead mill) will each seed soaked, then acetonitrile solvent extraction and determination of ten grains applied to the compound from each batch of 208 seed weight. 离心萃取液，并将等分试样的上清液稀释10000∶1，然后通过LC/MS分析。 The extract was centrifuged, and aliquots of the supernatant was diluted 10000:1, then by LC / MS analysis. 分析结果列于表8。 Analysis results are shown in Table 8.

表8用化合物208组合物涂覆的棉籽的测量 Table 8 Measurement cottonseed with composition was applied of Compound 208

*基于10次重复测定实施例F用包含化合物208、484、486、502、509或515的组合物涂覆的玉米种子批的制备步骤1：包含化合物208、484、486、502、509或515的易流动的悬浮液的制备使用下表9中显示的配方制备六种易流动的悬浮液，每种含有上述六种有效成分化合物中的一种。 * Based on 10 replicate measurements Example F was prepared to step corn seed lot composition comprising a compound coating 208,484,486,502,509 or 515 1: Contains compounds 208,484,486,502,509 or 515 9 display prepared using flowable suspension formulations prepared six table flowable suspensions, each containing any of the six active ingredient compounds is.

表9易流动的悬浮液中的成分的量 Table 9 amounts flowable suspension component

除有效成分化合物以外的所有成分都在实施例E中描述。 All components other than the active ingredient compound are described in Example E.

以实施例E，步骤1所描述的方法制备各化合物的易流动的悬浮液。 In Example E, Step 1. The method described for the preparation of the compounds of flowable suspension. 悬浮液中的颗粒粒径(即Dia，在表10中)也通过实施例E，步骤1中描述的方法分析。 Suspension particle size (i.e. Dia, in Table 10) is also the method described in Step 1 Analysis by Example E,. 湿磨后获得的粒径分布显示于表10中。 Particle size distribution obtained after wet milling are shown in Table 10.

表106种易流动的悬浮液的粒径 Table 106 kinds of flowable suspension particle size

*两次测量的平均值“＜”表示小于步骤2：用包含化合物208、484、486、502或515的单独组合物涂覆玉米种子将玉米种子(Pioneer 3146 Lot#C92FA(亲本)，65g)加入含有两个相反的提升叶片的不锈钢罐(12cm id，11cm深)中，所述提升叶片随罐转动而提升种子。 * Average of two measurements "<" means less than Step 2: Use a separate maize seed coating composition comprising a compound of 208,484,486,502 or 515 maize seeds (Pioneer 3146 Lot # C92FA (parent), 65g) solution containing two opposite lifting blades of stainless steel tanks (12cm id, 11cm depth), the lifting blades rotate with the tank and lifting the seed. 罐的方向与水平成40-45°角，并以110rpm机械旋转，这在罐内导致良好的混合和翻转运动。 Direction and level tank into a 40-45 ° angle, and 110rpm mechanical rotation, which leads to good mixing and turning motions in the tank.

按照实施例E，步骤2中描述的常规方法，将步骤1中制备的6种易流动的悬浮液各自直接喷到玉米种子的翻转床上。 According to a conventional method described in Example E, Step 2 as described in, Step 1 prepared six kinds of flowable suspension sprayed directly to the respective flip corn seed bed. 然后通过让种子在化学通风橱中干燥过夜而完成种子涂层的干燥。 Then by allowing seeds to dry overnight in a chemical fume hood and drying completed seed coating. 玉米种子上每种微粉化的化合物的标称3重量％涂层如表11所示得以实现。 Nominal 3 wt micronized corn seeds of each compound shown in Table 11 as percent of the coating can be achieved.

表11用单独化合物组合物涂覆的玉米种子的测量 Table measures 11 separate compound composition is coated with corn seeds

*基于10次重复测定实施例G用包含化合物208、276或483的组合物涂覆的棉籽批的制备步骤1：包含化合物208、276或483的易流动的悬浮液的制备使用与表9中显示相同的配方制备三种易流动的悬浮液，每种含有上述六种化合物中的一种。 * Based on 10 replicates EXAMPLE G Preparation of cottonseed batches step comprising a compound or composition is applied 208,276 483 1: prepared using the table contains 483 compounds of 208,276 or flowable suspension 9 displayed the same three formulations prepared flowable suspensions, each containing one of the six compounds. 以实施例E，步骤1所描述的方法制备各化合物的易流动的悬浮液。 In Example E, Step 1. The method described for the preparation of the compounds of flowable suspension. 悬浮液中的颗粒粒径(即Dia，在表10中)也通过实施例E，步骤1中描述的方法分析。 Suspension particle size (i.e. Dia, in Table 10) is also the method described in Step 1 Analysis by Example E,. 湿磨后获得的粒径分布显示于表12中。 Particle size distribution obtained after wet milling are shown in Table 12.

表123种易流动的悬浮液的粒径 Table 123 kinds of flowable suspension particle size

*两次测量的平均值“＜”表示小于步骤2：用包含化合物208、276或483的单独组合物涂覆棉籽将棉籽(Stoneville 4793 RR，33g)加入含有两个相反的提升叶片的不锈钢罐(6.5cm id，7.5cm深)中，所述提升叶片随罐转动而提升种子。 * The average of two measurements "<" means less than Step 2: Cottonseed with separate compositions comprising a compound coating will be 208,276 or 483 Cottonseed (Stoneville 4793 RR, 33g) was added containing two opposite lifting blades of stainless steel tank (6.5cm id, 7.5cm deep), the lifting blades rotating with the can ascend seed. 罐的方向与水平成40-45°角，并以100rpm机械旋转，这在罐内导致良好的混合和翻转运动。 Direction and level tank into a 40-45 ° angle, and 100rpm mechanical rotation, which leads to good mixing and turning motions in the tank.

按照实施例E，步骤2中描述的常规方法，将步骤1中制备的3种易流动的悬浮液各自直接喷到翻转的棉籽批上。 According to a conventional method described in Example E, Step 2 as described in, prepared in Step 1 will be three kinds of flowable suspension sprayed directly onto the respective cottonseed batches inverted. 然后通过让种子在化学通风橱中干燥过夜而完成种子涂层的干燥。 Then by allowing seeds to dry overnight in a chemical fume hood and drying completed seed coating. 棉籽上每种微粉化的化合物的标称3重量％涂层如表13所示得以实现。 Nominal 3 wt micronized on cottonseed each compound shown in Table 13.% coating is achieved.

表13用单独化合物组合物涂覆的棉籽的测量 Table 13 compound measured Cottonseed with separate compositions coated

*基于10次重复测定实施例H用包含化合物502的组合物涂覆的玉米种子批的制备步骤1：包含15％w/w化合物502的易流动的悬浮液的制备制备化合物502的15％易流动的悬浮液，除化合物以外，其含有实施例F，表9所列的相同成分。 * Based on 10 replicate measurements of maize seed lot of preparation steps in Example H was coated with a composition comprising a compound 502 of Example 1: Preparation of the compound prepared containing 15% w / w compound of flowable suspension of 502 502 15% Easy flowing suspension, except for compounds containing Example F, the same components in Table 9 are listed. 以实施例E，步骤1所描述的方法制备化合物502的易流动的悬浮液。 In Example E, Step 1 as described in the preparation of compound 502 of flowable suspension. 悬浮液中的颗粒粒径(即Dia，在表10中)也通过实施例E，步骤1中描述的方法分析。 Suspension particle size (i.e. Dia, in Table 10) is also the method described in Step 1 Analysis by Example E,. 湿磨后获得的粒径分布显示于表14中。 Particle size distribution obtained after wet milling are shown in Table 14.

表14易流动的悬浮液的颗径 Particle diameter of Table 14 flowable suspension

*两次测量的平均值“＜”表示小于步骤2：用包含化合物502的组合物涂覆玉米种子将玉米种子(Pioneer 34M94 Hybrid Field Corn，575g)加入含有两个相反的提升叶片的不锈钢罐(17cm id，16cm深)中，所述提升叶片随罐转动而提升种子。 * The average of two measurements "<" means less than Step 2: Corn seeds coated with a composition comprising a compound 502 corn seed (Pioneer 34M94 Hybrid Field Corn, 575g) was added containing two opposite lifting blades of stainless steel tanks ( 17cm id, 16cm depth), the lifting blades rotating with the can ascend seed. 罐的方向与水平成40-45°角，并以200rpm机械旋转，这在罐内导致良好的混合和翻转运动。 Direction and level tank into a 40-45 ° angle, and 200rpm mechanical rotation, which leads to good mixing and turning motions in the tank.

按照实施例E，步骤2中描述的常规方法，将步骤1中制备的15％w/w易流动的悬浮液直接喷到各翻转的玉米种子批上。 According to a conventional method described in Example E, Step Example 2, prepared in the step of 1 15% w / w flowable suspension sprayed directly onto the corn seed lots each flip. 然后通过让种子在化学通风橱中干燥过夜而完成种子涂层的干燥。 Then by allowing seeds to dry overnight in a chemical fume hood and drying completed seed coating. 玉米种子上微粉化的化合物502的标称0.15、0.29、0.58、1.09、1.75重量％涂层如表15所示得以实现。 On corn seed micronized compound 502 wt% of the nominal 0.15,0.29,0.58,1.09,1.75 coating as shown in Table 15 can be achieved. 经涂覆的种子上化合物502的平均Wt.％按照实施例E，步骤2中的方法通过LC/MS测量。 After the coated seeds of the compound average Wt 502% according to the method described in Example E, Step 2 by LC / MS measurement.

表15用化合物502组合物涂覆的玉米种子的测量 Measuring 15 by 502 meter compound composition coated maize seed

*基于10次重复测定以下本发明的生物实施例中的试验说明本发明的方法和组合物对于保护植物免受特定节肢动物害虫侵害的功效。 * Based on 10 replicate measurements of the test organisms in Example embodiments of the invention described below the method and compositions of the present invention for protecting plants from specific arthropod pests effect. 然而，由这些化合物提供的害虫防治保护并不限于这些种类。 However, the pest control protection afforded by these compounds is not limited to these species. 关于化合物的说明，参见索引表A。 About compound instructions, see the index table A. 在以下索引表中使用的缩写如下：t为叔，n为正，i为异，s为仲，c为环，Me为甲基，Et为乙基，Pr为丙基而Bu为丁基；相应地，i-Pr为异丙基，s-Bu为仲丁基等。 Abbreviations used in the following index table as follows: t is tertiary, n is normal, i is iso, s is secondary, c is a ring, Me is methyl, Et is ethyl, Pr is propyl and Bu is butyl; Accordingly, i-Pr is isopropyl, s-Bu is sec-butyl and the like. 缩写“Ex”表示“实施例”，其后跟着的数字表示该化合物在哪个实施例中制备。 Abbreviation "Ex" represents "Example", followed by the subsequent digital representation in which the compound prepared in the Examples.

索引表A Index Table A

除非特别指明，R1、R5和R8为H；除非特别指明，B为O；“CN”通过碳而非氮键合；例如，“CN-Ph”指氰基苯基，不是异氰基苯基。 Unless otherwise indicated, R1, R5 and R8 are H; unless otherwise indicated, B is O; "CN" is bonded through carbon, not nitrogen; e.g., "CN-Ph" refers cyanophenyl, not isocyano phenyl .

化合物 R3R2R4，R5R6R7m.p.(℃)165 Compound R3R2R4, R5R6R7m.p. (℃) 165 H 2-Cl CF32-(3-Cl-吡啶基) ＞250166 Et Et 2-Cl CF32-Cl-Ph 243-247167 Me Me 2-Cl CF32-Cl-Ph 234-235168 Et Et 2-Me CF32-Cl-Ph 237-238169 Me Me 2-Me CF32-Cl-Ph 225-226170 i-Pr H 2-Cl CF32-吡嗪基 242-243171 t-Bu H 2-Me-4-Br CF32-Cl-Ph ＞260172 CH(CH3)CH2OCH3H 2-Me CF32-(3-Cl-吡啶基) 176-177173 CH(CH3)CH2SCH3H 2-Me CF32-(3-Cl-吡啶基) 196-197174 CH(CH3)CH2OCH3H 2-Cl CF32-(3-Cl-吡啶基) 197-198175 CH(CH3)CH2SCH3H 2-Cl CF32-(3-Cl-吡啶基) 202-203176 i-Pr H 2-Me CF32-I-Ph 221-222177 i-Pr H 2-Cl CF32-I-Ph 238-240178 i-Pr H 2-Me CF32-(HC≡C)-Ph 215-217179 i-Pr H 2-Cl CF32-(HC≡C)-Ph 244-246180 i-Pr H 2-Me CF32-Cl-4-F-Ph 203-205181 i-Pr H 2-Cl CF32-Cl-4-F-Ph 218-219182 Et Et 2-Me CF32-Cl-Ph 243-247183 i-Pr H 2-Me CF32，6-二-Me-Ph 259-260184 i-Pr H 2-Cl CF32，6-二-Me-Ph 268-269185 i-Pr H 2-Me CF32，6-二-Cl-4-CN-Ph *186 i-Pr H 2-Me CF32-CN-Ph 225-235187 i-Pr H 2-Me CF32-(CF3O)-Ph 214-215188 i-Pr H 2-Cl CF32-(CF3O)-Ph 223-224189 i-Pr H 2-Me CF32-Br-4-F-Ph 202-203190 i-Pr H 2-Cl CF32-Br-4-F-Ph 222-223191 i-Pr H 2-Me CF32-(3-Me-吡唑基) 205-207192 Me H 2-Cl CF32-(3-Cl-吡啶基) 215-220193 CH2C≡CH H 2-Cl CF32-(3-Cl-吡啶基) 197-198194 Me H 2-Me CF32-(3-Cl-吡啶基) 193-196195 Et H 2-Me CF32-(3-Cl-吡啶基) 204-206196 CH2C≡CH H 2-Me CF32-(3-Cl-吡啶基) 177-178197 i-Pr H 2-Me CF34-(8-Cl-喹啉基) ＞250198 i-Pr H 2-Me CF34-(2-Me-喹啉基) ＞250199 i-Pr H 2-Cl CF34-(2-Me-喹啉基) ＞250 H 2-Cl CF32- (3-Cl- pyridyl)> 250166 Et Et 2-Cl CF32-Cl-Ph 243-247167 Me Me 2-Cl CF32-Cl-Ph 234-235168 Et Et 2-Me CF32-Cl -Ph 237-238169 Me Me 2-Me CF32-Cl-Ph 225-226170 i-Pr H 2-Cl CF32- pyrazinyl 242-243171 t-Bu H 2-Me-4-Br CF32-Cl-Ph> 260172 CH (CH3) CH2OCH3H 2-Me CF32- (3-Cl- pyridyl) 176-177173 CH (CH3) CH2SCH3H 2-Me CF32- (3-Cl- pyridyl) 196-197174 CH (CH3) CH2OCH3H 2- Cl CF32- (3-Cl- pyridyl) 197-198175 CH (CH3) CH2SCH3H 2-Cl CF32- (3-Cl- pyridyl) 202-203176 i-Pr H 2-Me CF32-I-Ph 221-222177 i-Pr H 2-Cl CF32-I-Ph 238-240178 i-Pr H 2-Me CF32- (HC≡C) -Ph 215-217179 i-Pr H 2-Cl CF32- (HC≡C) -Ph 244-246180 i-Pr H 2-Me CF32-Cl-4-F-Ph 203-205181 i-Pr H 2-Cl CF32-Cl-4-F-Ph 218-219182 Et Et 2-Me CF32-Cl- Ph 243-247183 i-Pr H 2-Me CF32,6- two -Me-Ph 259-260184 i-Pr H 2-Cl CF32,6- two -Me-Ph 268-269185 i-Pr H 2-Me CF32 , 6--Cl-4-CN-Ph * 186 i-Pr H 2-Me CF32-CN-Ph 225-235187 i-Pr H 2-Me CF32- (CF3O) -Ph 214-215188 i-Pr H 2-Cl CF32- (CF3O) -Ph 223-224189 i-Pr H 2-Me CF32-Br-4-F-Ph 202-203190 i-Pr H 2-Cl CF32-Br-4-F-Ph 222- 223191 i-Pr H 2-Me CF32- (3-Me- pyrazolyl) 205-207192 Me H 2-Cl CF32- (3-Cl- pyridyl) 215-220193 CH2C≡CH H 2-Cl CF32- ( 3-Cl- pyridyl) 197-198194 Me H 2-Me CF32- (3-Cl- pyridyl) 193-196195 Et H 2-Me CF32- (3-Cl- pyridyl) 204-206196 CH2C≡CH H 2-Me CF32- (3-Cl- pyridyl) 177-178197 i-Pr H 2-Me CF34- (8-Cl- quinolinyl)> 250198 i-Pr H 2-Me CF34- (2-Me- quinolinyl)> 250199 i-Pr H 2-Cl CF34- (2-Me- ​​quinolinyl)> 250

*1H NMR数据参见索引表B索引表B化合物1H NMR数据(CDCl3溶液，除非另外指明)a185 (DMSO-d6)δ1.03(d，6H)，2.18(s，3H)，3.92(m，1H)，7.22-7.30(m，2H)，7.35(m，1H)，7.62(dd，1H)，7.81(s，1H)，8.02(d，1H)，8.15(dd，1H)，8.55(dd，1H)，10.34(s，1H). * 1H NMR data refer to the index table Index Table B Compound B 1H NMR Data (CDCl3 solution unless otherwise indicated) a185 (DMSO-d6) δ1.03 (d, 6H), 2.18 (s, 3H), 3.92 (m, 1H ), 7.22-7.30 (m, 2H), 7.35 (m, 1H), 7.62 (dd, 1H), 7.81 (s, 1H), 8.02 (d, 1H), 8.15 (dd, 1H), 8.55 (dd, 1H), 10.34 (s, 1H).

217 (DMSO-d6)δ1.01(d，6H)，2.16(s，3H)，3.92(m，1H)，7.27(m，2H)，7.35(m，1H)，7.89(s，1H)，7.96(m，1H)，8.37(s，2H)，10.42(s，1H). 217 (DMSO-d6) δ1.01 (d, 6H), 2.16 (s, 3H), 3.92 (m, 1H), 7.27 (m, 2H), 7.35 (m, 1H), 7.89 (s, 1H), 7.96 (m, 1H), 8.37 (s, 2H), 10.42 (s, 1H).

241 (DMSO-d6)δ1.04(d，6H)，4.0(m，1H)，7.4(m，2H)，7.5(m，1H)，7.6(m1H)，7.78(d，2H)，8.0(d，2H)，8.2(d，1H)，10.7(bs，1H). 241 (DMSO-d6) δ1.04 (d, 6H), 4.0 (m, 1H), 7.4 (m, 2H), 7.5 (m, 1H), 7.6 (m1H), 7.78 (d, 2H), 8.0 ( d, 2H), 8.2 (d, 1H), 10.7 (bs, 1H).

242 (DMSO-d6)δ1.16(d，6H)，4.1(m，1H)，5.9(d，1H)，7.1(m，1H)，7.2(m，3H)，7.69(s，1H)，7.73(s，1H)，10.45(s，1H). 242 (DMSO-d6) δ1.16 (d, 6H), 4.1 (m, 1H), 5.9 (d, 1H), 7.1 (m, 1H), 7.2 (m, 3H), 7.69 (s, 1H), 7.73 (s, 1H), 10.45 (s, 1H).

243 (DMSO-d6)δ1.0(d，6H)，3.9(m，1H)，7.4(m，2H)，7.6(m，1H)，7.8(m，2H)，8.0(d，1H)，8.1(d，1H)，8.3(s，1H)，10.6(s，1H)244 (DMSO-d6)δ1.0(d，6H)，4.0(m，1H)，7.1(m，1H)，7.43(m，2H)，7.5(m，4H)，7.66(m，2H)，10.6(s，1H). 243 (DMSO-d6) δ1.0 (d, 6H), 3.9 (m, 1H), 7.4 (m, 2H), 7.6 (m, 1H), 7.8 (m, 2H), 8.0 (d, 1H), 8.1 (d, 1H), 8.3 (s, 1H), 10.6 (s, 1H) 244 (DMSO-d6) δ1.0 (d, 6H), 4.0 (m, 1H), 7.1 (m, 1H), 7.43 (m, 2H), 7.5 (m, 4H), 7.66 (m, 2H), 10.6 (s, 1H).

247 (DMSO-d6)δ1.02(d，6H)，2.18(s，3H)，3.9-4.0(m，1H)，7.2(m，1H)，7.4(m，1H)，7.8-7.9(m，2H)，8.0(d，2H)，8.3(s，1H)，10.3(s，1H). 247 (DMSO-d6) δ1.02 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (m, 1H), 7.2 (m, 1H), 7.4 (m, 1H), 7.8-7.9 (m , 2H), 8.0 (d, 2H), 8.3 (s, 1H), 10.3 (s, 1H).

248 (DMSO-d6)δ1.02(d，6H)，2.18(s，3H)，3.9-4.0(m，1H)，7.2(m，1H)，7.4(m，1H)，7.8-7.9(m，2H)，8.0(d，2H)，8.3(s，1H)，10.3(s，1H). 248 (DMSO-d6) δ1.02 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (m, 1H), 7.2 (m, 1H), 7.4 (m, 1H), 7.8-7.9 (m , 2H), 8.0 (d, 2H), 8.3 (s, 1H), 10.3 (s, 1H).

249 (DMSO-d6)δ1.04(d，6H)，4.0(m，1H)，7.4(m，2H)，7.76(s，1H)，7.7(m，1H)，7.74(m，1H)，7.9(m，1H)，7.97(d，1H)，8.07(s，1H)，8.2(m，1H)，10.7(bs，1H). 249 (DMSO-d6) δ1.04 (d, 6H), 4.0 (m, 1H), 7.4 (m, 2H), 7.76 (s, 1H), 7.7 (m, 1H), 7.74 (m, 1H), 7.9 (m, 1H), 7.97 (d, 1H), 8.07 (s, 1H), 8.2 (m, 1H), 10.7 (bs, 1H).

264 (DMSO-d6)δ1.0(d，6H)，2.01(s，3H)，2.17(s，3H)，3.9(m，1H)，7.3(m，2H)，7.3-7.4(m，1H)，7.8-7.9(s，1H)，7.9-8.0(m，2H)，8.1-8.2(s，1H)，10.3-10.4(s，1H). 264 (DMSO-d6) δ1.0 (d, 6H), 2.01 (s, 3H), 2.17 (s, 3H), 3.9 (m, 1H), 7.3 (m, 2H), 7.3-7.4 (m, 1H ), 7.8-7.9 (s, 1H), 7.9-8.0 (m, 2H), 8.1-8.2 (s, 1H), 10.3-10.4 (s, 1H).

273 (DMSO-d6)δ1.21(d，6H)，2.24(s，3H)，4.1-4.3(m，1H)，5.9(d，1H)，7.02(d，1H)，7.1-7.6(m，7H)，7.78(s，1H)，10.0(br s，1H) 273 (DMSO-d6) δ1.21 (d, 6H), 2.24 (s, 3H), 4.1-4.3 (m, 1H), 5.9 (d, 1H), 7.02 (d, 1H), 7.1-7.6 (m , 7H), 7.78 (s, 1H), 10.0 (br s, 1H)

化合物1H NMR数据(CDCl3溶液，除非另外指明)a274 (DMSO-d6)δ1.03(d，6H)，1.94(s，3H)，2.14(s，3H)，3.9-4.0(m，1H)，7.1-7.4(m，8H)，7.8(s，1H)，7.9-8.0(d，1H)，10.0(s，1H). Compound 1H NMR Data (CDCl3 solution unless otherwise indicated) a274 (DMSO-d6) δ1.03 (d, 6H), 1.94 (s, 3H), 2.14 (s, 3H), 3.9-4.0 (m, 1H), 7.1-7.4 (m, 8H), 7.8 (s, 1H), 7.9-8.0 (d, 1H), 10.0 (s, 1H).

275 (DMSO-d6)δ1.04(d，6H)，2.18(s，3H)，3.9-4.0(m，1H)，7.2-7.4(m，6H)，7.4-7.6(m，2H)，7.9(s，1H)，7.9-8.0(d，1H)，10.1(br s，1H). 275 (DMSO-d6) δ1.04 (d, 6H), 2.18 (s, 3H), 3.9-4.0 (m, 1H), 7.2-7.4 (m, 6H), 7.4-7.6 (m, 2H), 7.9 (s, 1H), 7.9-8.0 (d, 1H), 10.1 (br s, 1H).

278 δ1.20(d，6H)，2.19(s，3H)，4.2(m，1H)，5.9-6.0(d，1H)，7.1-7.5(m，8H)，10.4-10.5(s，1H). 278 δ1.20 (d, 6H), 2.19 (s, 3H), 4.2 (m, 1H), 5.9-6.0 (d, 1H), 7.1-7.5 (m, 8H), 10.4-10.5 (s, 1H) .

314 (DMSO-d6)δ1.03(d，6H)，2.18(s，3H)，3.31(s，3H)，3.9-4.0(m，1H)，7.2-7.3(m，2H)，7.3-7.4(m，1H)，7.81(s，1H)，7.9(d，1H)，8.0(br d，1H)，8.1(dd，1H)，8.3(d，1H)，10.3(s，1H). 314 (DMSO-d6) δ1.03 (d, 6H), 2.18 (s, 3H), 3.31 (s, 3H), 3.9-4.0 (m, 1H), 7.2-7.3 (m, 2H), 7.3-7.4 (m, 1H), 7.81 (s, 1H), 7.9 (d, 1H), 8.0 (br d, 1H), 8.1 (dd, 1H), 8.3 (d, 1H), 10.3 (s, 1H).

398 δ2.57(t，2H)，3.57(q，2H)，6.25(t，1H)，7.18-7.53(m，8H)，9.17(s，1H)399 δ1.23(d，6H)，4.13(m，1H)，5.92(d，1H)，7.35(m，1H)，7.39(s，1H)7.42(m，2H)，7.92(d，1H)，8.51(d，1H)，10.23(br s，1H). 398 δ2.57 (t, 2H), 3.57 (q, 2H), 6.25 (t, 1H), 7.18-7.53 (m, 8H), 9.17 (s, 1H) 399 δ1.23 (d, 6H), 4.13 (m, 1H), 5.92 (d, 1H), 7.35 (m, 1H), 7.39 (s, 1H) 7.42 (m, 2H), 7.92 (d, 1H), 8.51 (d, 1H), 10.23 (br s, 1H).

402 δ1.13(d，6H)，4.15(m，1H)，5.99(d，1H)，7.40(m，1H)，7.41(m，1H)，7.63(m，1H)，7.80(s，1H)，7.90(d，1H)，8.48(d，1H)，10.2(br s，1H). 402 δ1.13 (d, 6H), 4.15 (m, 1H), 5.99 (d, 1H), 7.40 (m, 1H), 7.41 (m, 1H), 7.63 (m, 1H), 7.80 (s, 1H ), 7.90 (d, 1H), 8.48 (d, 1H), 10.2 (br s, 1H).

562 δ1.22(d，6H)，2.18(s，3H)，4.15(m，1H)，4.37(s，1H)，5.91(d，1H)，7.20(m，4H)，7.30(m，1H)，7.40(m，1H)，7.52(m，2H)，7.96(s，1H)，10.23(s，1H). 562 δ1.22 (d, 6H), 2.18 (s, 3H), 4.15 (m, 1H), 4.37 (s, 1H), 5.91 (d, 1H), 7.20 (m, 4H), 7.30 (m, 1H ), 7.40 (m, 1H), 7.52 (m, 2H), 7.96 (s, 1H), 10.23 (s, 1H).

563 (DMSO-d6)δ1.05(d，6H)，2.15(s，3H)，3.74(s，2H)，3.93(m，1H)，7.26-7.70(m，8H)，8.05(s，1H)，8.35(br s，2H)，10.45(s，1H). 563 (DMSO-d6) δ1.05 (d, 6H), 2.15 (s, 3H), 3.74 (s, 2H), 3.93 (m, 1H), 7.26-7.70 (m, 8H), 8.05 (s, 1H ), 8.35 (br s, 2H), 10.45 (s, 1H).

572 δ1.20(d，6H)，2.01(s，3H)，2.72(d，3H)，4.13(m，1H)，6.01(d，1H)，6.45(s，1H)，7.17(m，5H)，7.51(m，2H)，7.63(m，1H)，10.41(s，1H)，586 (DMSO-d6)δ1.04(d，6H)，2.32(s，3H)，3.91(m，1H)，7.44-7.64(m，4H)，7.77(s，1H)，8.07(d，1H)，8.27(d，1H)，8.42(d，1H)，10.6(s，1H). 572 δ1.20 (d, 6H), 2.01 (s, 3H), 2.72 (d, 3H), 4.13 (m, 1H), 6.01 (d, 1H), 6.45 (s, 1H), 7.17 (m, 5H ), 7.51 (m, 2H), 7.63 (m, 1H), 10.41 (s, 1H), 586 (DMSO-d6) δ1.04 (d, 6H), 2.32 (s, 3H), 3.91 (m, 1H ), 7.44-7.64 (m, 4H), 7.77 (s, 1H), 8.07 (d, 1H), 8.27 (d, 1H), 8.42 (d, 1H), 10.6 (s, 1H).

590 (DMSO-d6)δ1.03(d，6H)，3.88(m，1H)，7.65(dd，1H)，7.88(s，1H)，8.18(s，1H)，8.22(d，1H)，8.48-8.57(m，3H)，10.95(s，1H). 590 (DMSO-d6) δ1.03 (d, 6H), 3.88 (m, 1H), 7.65 (dd, 1H), 7.88 (s, 1H), 8.18 (s, 1H), 8.22 (d, 1H), 8.48-8.57 (m, 3H), 10.95 (s, 1H).

592 δ1.24(d，6H)，4.22(m，1H)，5.98(br d，1H)，7.30-7.55(m，6H)，7.78(d，1H)，7.99(d，1H)，11.15(s，1H). 592 δ1.24 (d, 6H), 4.22 (m, 1H), 5.98 (br d, 1H), 7.30-7.55 (m, 6H), 7.78 (d, 1H), 7.99 (d, 1H), 11.15 ( s, 1H).

603 δ2.16(s，3H)，7.1-7.3(不明显，1H)，7.40(d，1H)，7.47(dd，1H)，7.93(dd，1H)，8.03(d，1H)，8.5(dd，1H). 603 δ2.16 (s, 3H), 7.1-7.3 (obvious, 1H), 7.40 (d, 1H), 7.47 (dd, 1H), 7.93 (dd, 1H), 8.03 (d, 1H), 8.5 ( dd, 1H).

610 (DMSO-d6)δ1.04(m，6H)，4.08(s，3H) 8.18(m，2H)，8.22(d，1H)，8.47(dd，1H)，8.58(d，1H)，9.17(d，1H)，9.39(d，1H)，11.48(s，1H). 610 (DMSO-d6) δ1.04 (m, 6H), 4.08 (s, 3H) 8.18 (m, 2H), 8.22 (d, 1H), 8.47 (dd, 1H), 8.58 (d, 1H), 9.17 (d, 1H), 9.39 (d, 1H), 11.48 (s, 1H).

611 (DMSO-d6)δ1.04(m，6H)，2.50(s，3H)，4.09(s，3H)，8.12(d，1H)，8.17(s，1H)，8.34(d，1H)，8.37-8.52(m，2H)，9.15(d，1H)，9.37(d，1H)，11.11(s，1H). 611 (DMSO-d6) δ1.04 (m, 6H), 2.50 (s, 3H), 4.09 (s, 3H), 8.12 (d, 1H), 8.17 (s, 1H), 8.34 (d, 1H), 8.37-8.52 (m, 2H), 9.15 (d, 1H), 9.37 (d, 1H), 11.11 (s, 1H).

638 δ1.30(t，3H)，2.32(s，3H)，3.55(q，2H)，6.23(br t，1H)，7.30(s，1H)，7.42(dd，1H)，7.91(d，1H)，8.20(表观s，2H)，8.52(d，1H)，10.92(s，1H). 638 δ1.30 (t, 3H), 2.32 (s, 3H), 3.55 (q, 2H), 6.23 (br t, 1H), 7.30 (s, 1H), 7.42 (dd, 1H), 7.91 (d, 1H), 8.20 (apparent s, 2H), 8.52 (d, 1H), 10.92 (s, 1H).

化合物1H NMR数据(CDCl3溶液，除非另外指明)a639 δ2.21(s，3H)，2.90(s，3H)，3.12(s，3H)，7.42(m，2H)，7.92(d，1H)，7.92(d，1H)，8.00(d，1H)，8.50(d，1H)，9.92(br s，1H). Compound 1H NMR Data (CDCl3 solution unless otherwise indicated) a639 δ2.21 (s, 3H), 2.90 (s, 3H), 3.12 (s, 3H), 7.42 (m, 2H), 7.92 (d, 1H), 7.92 (d, 1H), 8.00 (d, 1H), 8.50 (d, 1H), 9.92 (br s, 1H).

640 δ2.32(s，3H)，4.02(t，2H)，5.18-5.30(m，2H)，5.82-5.98(m，1H)，7.37(s，1H)，7.43(dd，1H)，7.50(br t，1H)，7.92(d，1H)，8.17(s，1H)，8.37(d，1H)，8.52(d，1H)，11.12(br s，1H). 640 δ2.32 (s, 3H), 4.02 (t, 2H), 5.18-5.30 (m, 2H), 5.82-5.98 (m, 1H), 7.37 (s, 1H), 7.43 (dd, 1H), 7.50 (br t, 1H), 7.92 (d, 1H), 8.17 (s, 1H), 8.37 (d, 1H), 8.52 (d, 1H), 11.12 (br s, 1H).

641 δ0.91(t，3H)，1.63(m，2H)，2.31(s，3H)，3.40(q，2H)，6.83(br t，1H)，7.35(s，1H)，7.42(dd，1H)，7.91(d，1H)，8.17(d，1H)，8.24(d，1H)，8.52(d，1H)，11.03(s，1H). 641 δ0.91 (t, 3H), 1.63 (m, 2H), 2.31 (s, 3H), 3.40 (q, 2H), 6.83 (br t, 1H), 7.35 (s, 1H), 7.42 (dd, 1H), 7.91 (d, 1H), 8.17 (d, 1H), 8.24 (d, 1H), 8.52 (d, 1H), 11.03 (s, 1H).

642 δ1.38(d，3H)，2.14(s，3H)，2.35(s，3H)，2.72(m，2H)，4.38(m，1H)，6.93(br d，1H)，7.33(s，1H)，7.43(dd，1H)，7.91(d，1H)，8.18(d，1H)，8.28(d，1H)，8.52(d，1H)，10.93(s，1H). 642 δ1.38 (d, 3H), 2.14 (s, 3H), 2.35 (s, 3H), 2.72 (m, 2H), 4.38 (m, 1H), 6.93 (br d, 1H), 7.33 (s, 1H), 7.43 (dd, 1H), 7.91 (d, 1H), 8.18 (d, 1H), 8.28 (d, 1H), 8.52 (d, 1H), 10.93 (s, 1H).

643 (DMSO-d6)δ2.32(s，3H)，2.70(s，3H)，7.63(m，2H)，7.78(br s，1H)，8.18(br s，1H)，8.21(d，1H)，8.27(br s，1H)，8.58(m，2H). 643 (DMSO-d6) δ2.32 (s, 3H), 2.70 (s, 3H), 7.63 (m, 2H), 7.78 (br s, 1H), 8.18 (br s, 1H), 8.21 (d, 1H ), 8.27 (br s, 1H), 8.58 (m, 2H).

644 (DMSO-d6)δ1.25(s，9H)，2.31(s，3H)，7.64(dd，1H)，7.79(s，1H)，8.03(br s，2H)，8.22(d，1H)，8.28(s，1H)，8.54(d，1H)，10.62(s，1H). 644 (DMSO-d6) δ1.25 (s, 9H), 2.31 (s, 3H), 7.64 (dd, 1H), 7.79 (s, 1H), 8.03 (br s, 2H), 8.22 (d, 1H) , 8.28 (s, 1H), 8.54 (d, 1H), 10.62 (s, 1H).

654 δ2.33(s，3H)，2.75(br s，6H)，6.9(br s，1H)，7.33(s，1H)，7.43(dd，1H)，7.91(d，1H)，8.19(br s，1H)，8.23(s，1H)，8.50(d，1H)，10.70(br s，1H). 654 δ2.33 (s, 3H), 2.75 (br s, 6H), 6.9 (br s, 1H), 7.33 (s, 1H), 7.43 (dd, 1H), 7.91 (d, 1H), 8.19 (br s, 1H), 8.23 ​​(s, 1H), 8.50 (d, 1H), 10.70 (br s, 1H).

735 δ1.39(d，6H)，2.81(d，3H)，4.95(m，1H)，6.59(s，1H)，6.62(q，1H)，7.12(s，1H)，7.24(s，1H)，7.26(t，1H)，7.80(d，1H)，8.40(d，1H)，9.56(br s，1H). 735 δ1.39 (d, 6H), 2.81 (d, 3H), 4.95 (m, 1H), 6.59 (s, 1H), 6.62 (q, 1H), 7.12 (s, 1H), 7.24 (s, 1H ), 7.26 (t, 1H), 7.80 (d, 1H), 8.40 (d, 1H), 9.56 (br s, 1H).

772 δ1.24(d，6H)，2.22(s，3H)，4.20(m，1H)，6.10(d，1H)，7.35(s，1H)，7.44(t，1H)，7.55(s，2H)，7.87(s，1H)，8.48(d，1H)，10.7(s，1H). 772 δ1.24 (d, 6H), 2.22 (s, 3H), 4.20 (m, 1H), 6.10 (d, 1H), 7.35 (s, 1H), 7.44 (t, 1H), 7.55 (s, 2H ), 7.87 (s, 1H), 8.48 (d, 1H), 10.7 (s, 1H).

780 δ2.91(d，3H)，6.3(m，1H)，6.77(d，1H)，7.3(不清楚，1H)，7.3-7.4(m，2H)，7.8-7.9(d，1H)，8.5(d，1H)，9.6-9.7(br s，1H). 780 δ2.91 (d, 3H), 6.3 (m, 1H), 6.77 (d, 1H), 7.3 (unclear, 1H), 7.3-7.4 (m, 2H), 7.8-7.9 (d, 1H), 8.5 (d, 1H), 9.6-9.7 (br s, 1H).

802 (DMSO-d6)δ7.1(d，1H)，7.5-7.7(m，3H)，7.8(m，2H)，8.1-8.2(d，1H)，8.5(d，1H)，10.5(br s，1H). 802 (DMSO-d6) δ7.1 (d, 1H), 7.5-7.7 (m, 3H), 7.8 (m, 2H), 8.1-8.2 (d, 1H), 8.5 (d, 1H), 10.5 (br s, 1H).

803 (DMSO-d6)δ1.03(d，6H)，3.9(m，1H)，7.1(d，1H)，7.4-7.5(d，1H)，7.6(dd，1H)，7.8(d，1H)，8.2(d，1H)，8.2(m，1H)，8.5(d，1H)，10.5(br s，1H). 803 (DMSO-d6) δ1.03 (d, 6H), 3.9 (m, 1H), 7.1 (d, 1H), 7.4-7.5 (d, 1H), 7.6 (dd, 1H), 7.8 (d, 1H ), 8.2 (d, 1H), 8.2 (m, 1H), 8.5 (d, 1H), 10.5 (br s, 1H).

804 δ2.78(s，3H)，3.04(s，3H)，6.9(d，1H)，7.1(d，1H)，7.29(d，1H)，7.3-7.4(dd，1H)，7.8-7.9(d，1H)，8.5(d，1H)，9.8(br s，1H). 804 δ2.78 (s, 3H), 3.04 (s, 3H), 6.9 (d, 1H), 7.1 (d, 1H), 7.29 (d, 1H), 7.3-7.4 (dd, 1H), 7.8-7.9 (d, 1H), 8.5 (d, 1H), 9.8 (br s, 1H).

805 δ2.18(s，3H)，5.7(br s，1H)，6.2(br s，1H)，6.7(d，1H)，7.3(m，1H)，7.3-7.4(dd，1H)，7.8-7.9(d，1H)，8.4-8.5(d，1H)，10.0(br s，1H). 805 δ2.18 (s, 3H), 5.7 (br s, 1H), 6.2 (br s, 1H), 6.7 (d, 1H), 7.3 (m, 1H), 7.3-7.4 (dd, 1H), 7.8 -7.9 (d, 1H), 8.4-8.5 (d, 1H), 10.0 (br s, 1H).

806 δ1.23(d，6H)，2.19(s，3H)，4.2(m，1H)，5.9(br s，1H)，6.7(d，1H)，7.21(d，1H)，7.26(不清楚，1H)，7.3-7.4(dd，1H)，7.8-7.9(d，1H)，8.4-8.5(d，1H)，10.1(br s，1H). 806 δ1.23 (d, 6H), 2.19 (s, 3H), 4.2 (m, 1H), 5.9 (br s, 1H), 6.7 (d, 1H), 7.21 (d, 1H), 7.26 (not clear , 1H), 7.3-7.4 (dd, 1H), 7.8-7.9 (d, 1H), 8.4-8.5 (d, 1H), 10.1 (br s, 1H).

化合物1H NMR数据(CDCl3溶液，除非特别指明)a807 δ2.20(s，3H)，2.96(d，3H)，6.1(br s，1H)，6.65(d，1H)，7.2(d，1H)，7.26(不清楚，1H)，7.3-7.4(dd，1H)，7.8-7.9(d，1H)，8.4-8.5(d，1H)，10.1(brs，1H). Compound 1H NMR Data (CDCl3 solution, unless otherwise indicated) a807 δ2.20 (s, 3H), 2.96 (d, 3H), 6.1 (br s, 1H), 6.65 (d, 1H), 7.2 (d, 1H) , 7.26 (unclear, 1H), 7.3-7.4 (dd, 1H), 7.8-7.9 (d, 1H), 8.4-8.5 (d, 1H), 10.1 (brs, 1H).

808 δ2.06(s，3H)，2.78(s，3)，3.08(s，3H)，6.9(d，1H)，7.0(s，1H)，7.1(s，1H)，7.3-7.4(dd，1H)，7.8-7.9(d，1H)，8.4-8.5(d，1H)，9.7-9.8(br s，1H). 808 δ2.06 (s, 3H), 2.78 (s, 3), 3.08 (s, 3H), 6.9 (d, 1H), 7.0 (s, 1H), 7.1 (s, 1H), 7.3-7.4 (dd , 1H), 7.8-7.9 (d, 1H), 8.4-8.5 (d, 1H), 9.7-9.8 (br s, 1H).

814 (DMSO-d6)δ2.65(d，3H)，7.52(d，1H)，7.6-7.8(m，2H)，7.9(d，1H)，8.0-8.1(t，1H)，8.3-8.4(m，1H)，8.4(d，1H)，10.7(br s，1H). 814 (DMSO-d6) δ2.65 (d, 3H), 7.52 (d, 1H), 7.6-7.8 (m, 2H), 7.9 (d, 1H), 8.0-8.1 (t, 1H), 8.3-8.4 (m, 1H), 8.4 (d, 1H), 10.7 (br s, 1H).

838 (DMSO-d6)δ2.18(s，3H)，7.41(d，1H)，7.5(m，2H)，7.67(s，1H)，7.7(m，1H)，7.8(s，1H)，8.0-8.1(t，1H)，8.4(d，1H)，10.4-10.5(br s，1H). 838 (DMSO-d6) δ2.18 (s, 3H), 7.41 (d, 1H), 7.5 (m, 2H), 7.67 (s, 1H), 7.7 (m, 1H), 7.8 (s, 1H), 8.0-8.1 (t, 1H), 8.4 (d, 1H), 10.4-10.5 (br s, 1H).

839 (DMSO-d6)δ2.18(s，3H)，2.66(d，3H)，7.35(d，1H)，7.49(d，1H)，7.69(s，1H)，7.7-7.8(m，1H)，8.0-8.1(t，1H)，8.3(m，1H)，8.4(d，1H)，10.4-10.5(br s，1H). 839 (DMSO-d6) δ2.18 (s, 3H), 2.66 (d, 3H), 7.35 (d, 1H), 7.49 (d, 1H), 7.69 (s, 1H), 7.7-7.8 (m, 1H ), 8.0-8.1 (t, 1H), 8.3 (m, 1H), 8.4 (d, 1H), 10.4-10.5 (br s, 1H).

840 δ2.00(s，3H)，2.75(s，3H)，3.09(s，3H)，6.99(d，1H)，7.03(s，1H)，7.4-7.5(m，1H)，7.5-7.6(t，1H)，7.76(d，1H)，8.4(d，1H)，10.4-10.5(br s，1H). 840 δ2.00 (s, 3H), 2.75 (s, 3H), 3.09 (s, 3H), 6.99 (d, 1H), 7.03 (s, 1H), 7.4-7.5 (m, 1H), 7.5-7.6 (t, 1H), 7.76 (d, 1H), 8.4 (d, 1H), 10.4-10.5 (br s, 1H).

841 (DMSO-d6)δ1.02(d，6H)，2.19(s，3H)，3.9(m，1H)，7.30(s，1H)，7.48(d，1H)，7.6-7.8(m，2H)，8.0(t，1H)，8.1(d，1H)，8.4(d，1H)，10.4(br s，1H). 841 (DMSO-d6) δ1.02 (d, 6H), 2.19 (s, 3H), 3.9 (m, 1H), 7.30 (s, 1H), 7.48 (d, 1H), 7.6-7.8 (m, 2H ), 8.0 (t, 1H), 8.1 (d, 1H), 8.4 (d, 1H), 10.4 (br s, 1H).

842 (DMSO-d6)δ7.56(d，1H)，7.6(s，1H)，7.7-7.8(m，2H)7.9(m，2H)，8.0-8.1(t，1H)，8.4(d，1H)，10.6-10.7(br s，1H). 842 (DMSO-d6) δ7.56 (d, 1H), 7.6 (s, 1H), 7.7-7.8 (m, 2H) 7.9 (m, 2H), 8.0-8.1 (t, 1H), 8.4 (d, 1H), 10.6-10.7 (br s, 1H).

843 δ2.79(s，3H)，3.08(s，3H)，7.09(d，1H)，725(d，1H)，7.4-7.5(m，1H)，7.5-7.6(t，1H)，7.78(s，1H)，8.4(d，1H)，10.5(br s，1H). 843 δ2.79 (s, 3H), 3.08 (s, 3H), 7.09 (d, 1H), 725 (d, 1H), 7.4-7.5 (m, 1H), 7.5-7.6 (t, 1H), 7.78 (s, 1H), 8.4 (d, 1H), 10.5 (br s, 1H).

844 (DMSO-d6)δ1.01(d，6H)，3.9(m，1H)，7.46(d，1H)，7.7(m，1H)，7.8(s，1H)，7.85(d，1H)，8.0(t，1H)，8.2-8.3(d，1H)，8.4(d，1H)，10.6-10.7(br s，1H). 844 (DMSO-d6) δ1.01 (d, 6H), 3.9 (m, 1H), 7.46 (d, 1H), 7.7 (m, 1H), 7.8 (s, 1H), 7.85 (d, 1H), 8.0 (t, 1H), 8.2-8.3 (d, 1H), 8.4 (d, 1H), 10.6-10.7 (br s, 1H).

845 (DMSO-d6)δ7.39(s，1H)，7.55(d，1H)，7.4(s，1H)，7.4-7.5(m，1H)，7.8(s，1H)，7.85(d，1H)，8.0(t，1H)，8.4(d，1H)，10.5(br s，1H). 845 (DMSO-d6) δ7.39 (s, 1H), 7.55 (d, 1H), 7.4 (s, 1H), 7.4-7.5 (m, 1H), 7.8 (s, 1H), 7.85 (d, 1H ), 8.0 (t, 1H), 8.4 (d, 1H), 10.5 (br s, 1H).

846 (DMSO-d6)δ2.66(d，3H)，7.40(s，1H)，7.51(d，1H)，7.6-7.7(m，1H)，7.84(d，1H)，8.0(t，1H)，8.3-8.4(m，1H)，8.4(d，1H)，10.5-10.6(br s，1H). 846 (DMSO-d6) δ2.66 (d, 3H), 7.40 (s, 1H), 7.51 (d, 1H), 7.6-7.7 (m, 1H), 7.84 (d, 1H), 8.0 (t, 1H ), 8.3-8.4 (m, 1H), 8.4 (d, 1H), 10.5-10.6 (br s, 1H).

847 δ2.80(s，3H)，3.07(s，3H)，7.10(s，1H)，7.31(d，1H)，7.35(s，1H)，7.4(m，1H)，7.5-7.6(t，1H)，8.4(d，1H)，9.5(br s，1H). 847 δ2.80 (s, 3H), 3.07 (s, 3H), 7.10 (s, 1H), 7.31 (d, 1H), 7.35 (s, 1H), 7.4 (m, 1H), 7.5-7.6 (t , 1H), 8.4 (d, 1H), 9.5 (br s, 1H).

848 (DMSO-d6)δ1.02(d，6H)，3.9(m，1H)，7.45(表观s，2H)，7.6-7.7(m，1H)，7.84(d，1H)，7.9-8.0(t，1H)，8.2(d，1H)，8.36(d，1H)，10.5(br s，1H). 848 (DMSO-d6) δ1.02 (d, 6H), 3.9 (m, 1H), 7.45 (apparent s, 2H), 7.6-7.7 (m, 1H), 7.84 (d, 1H), 7.9-8.0 (t, 1H), 8.2 (d, 1H), 8.36 (d, 1H), 10.5 (br s, 1H).

849 (DMSO-d6)δ2.17(s，3H)，7.33(s，1H)，7.4(d，1H)，7.5(m，2H)，7.6-7.7(m，1H)，7.9(s，1H)，8.0(t，1H)，8.4(d，1H)，10.3(br s，1H). 849 (DMSO-d6) δ2.17 (s, 3H), 7.33 (s, 1H), 7.4 (d, 1H), 7.5 (m, 2H), 7.6-7.7 (m, 1H), 7.9 (s, 1H ), 8.0 (t, 1H), 8.4 (d, 1H), 10.3 (br s, 1H).

850 (DMSO-d6)δ2.17(s，3H)，2.67(d，3H)，7.3-7.4(m，2H)，7.5(d，1H)，7.6-7.7(m，1H)，8.0(t，1H)，8.2-8.3(m，1H)，8.4(d，1H)，10.3(br s，1H). 850 (DMSO-d6) δ2.17 (s, 3H), 2.67 (d, 3H), 7.3-7.4 (m, 2H), 7.5 (d, 1H), 7.6-7.7 (m, 1H), 8.0 (t , 1H), 8.2-8.3 (m, 1H), 8.4 (d, 1H), 10.3 (br s, 1H).

化合物1H NMR数据(CDCl3溶液，除非另外指明)a851 δ2.08(s，3H)，2.79(s，3H)，3.09(s，3H)，6.99(d，1H)，7.11(s，1H)，7.28(d，1H)，7.4(m，1H)，7.5-7.6(t，1H)，8.3-8.4(d，1H)，9.8(br s，1H). Compound 1H NMR Data (CDCl3 solution unless otherwise indicated) a851 δ2.08 (s, 3H), 2.79 (s, 3H), 3.09 (s, 3H), 6.99 (d, 1H), 7.11 (s, 1H), 7.28 (d, 1H), 7.4 (m, 1H), 7.5-7.6 (t, 1H), 8.3-8.4 (d, 1H), 9.8 (br s, 1H).

852 (DMSO-d6)δ1.03(d，6H)，2.17(s，3H)，3.9(m，1H)，7.3(d，1H)，7.37(s，1H)，7.5(d，1H)，7.6-7.7(m，1H)，7.9-8.0(t，1H)，8.1(d，1H)，8.3-8.4(d，1H)，10.2-10.3(dr s，1H). 852 (DMSO-d6) δ1.03 (d, 6H), 2.17 (s, 3H), 3.9 (m, 1H), 7.3 (d, 1H), 7.37 (s, 1H), 7.5 (d, 1H), 7.6-7.7 (m, 1H), 7.9-8.0 (t, 1H), 8.1 (d, 1H), 8.3-8.4 (d, 1H), 10.2-10.3 (dr s, 1H).

a1H NMR数据为ppm来自四甲基硅烷低磁场。 a1H NMR data in ppm downfield from tetramethylsilane. 偶联用以下符号表示：(s)-单峰，(d)-双峰，(t)-三重峰，(q)-四重峰，(m)-多重峰，(dd)-双重的双峰，(dt)-双重的三重峰，(br s)-宽单峰。 Coupled with the following notation: (s) - a single peak, (d) - doublet, (t) - triplet, (q) - quartet, (m) - multiplet, (dd) - double double peak, (dt) - double triplet, (br s) - broad singlet.

本发明的生物实施例试验A将如实施例E中所述制备的来自标称1％、标称2％和标称3％浓度批的用化合物208的组合物涂覆的棉籽和用以对照的未经处理的种子种植在无菌黄樟土(Sassafras soil)罐中，并在28℃ 16小时光照和24℃8小时黑暗和50％相对湿度的生长箱中生长。 EXAMPLE A test organisms embodiment of the present invention will be described as prepared in Example E from nominal 1%, 2% and Nominal 3% concentration batches of nominal composition coated cottonseed and compound 208 for Comparative Examples without seed treatment planted in sterile soil sassafras (Sassafras soil) pots and grown at 28 ℃ 16 hours of light and 24 ℃ 8 hours of darkness and 50% relative humidity growth chamber. 31天后，从每个种子批中选择都具有真叶的两株植物，除去它们的子叶。 31 days later, select seeds from each batch of two plants have true leaves, remove their cotyledons. 将银叶粉虱(Bemisia argentifolii)成虫加于植物上产卵，然后将罩有薄纸的塑料圆筒与罐适合。 The silverleaf whitefly (Bemisia argentifolii) spawning adults is applied to the plant, then cover with plastic cylinder has a tissue suitable tank. 三天后，除去成虫，检查叶子以确定卵沉积。 Three days later, the adults was removed, leaves checked to determine egg deposition. 15天后(约卵孵化后六天)，从植物上除去受侵染的叶子，并通过计数叶子下面的死蛹和活蛹而确定49天结果。 15 days later (after about six days the eggs hatch), remove the leaves from the plants infested, and by counting the dead leaves beneath live pupae and pupae and 49 days to determine the outcome. 再将银叶粉虱成虫引入植物叶子的上面进行第二轮产卵，并且如前相同地将罩有薄纸的塑料圆筒与罐适合。 Then silverleaf whitefly adults above the leaves of plants were introduced a second round of spawning, and have to be the same as before tissue plastic cylinder cover for the tank. 三天后，除去成虫，检查叶子以确定卵沉积。 Three days later, the adults was removed, leaves checked to determine egg deposition. 十四天后(约卵孵化后六天)，从植物上除去受侵染的叶子，并通过计数叶子下面的死蛹和活蛹而确定66天的结果。 After fourteen days (after about six days the eggs hatch), remove the leaves from the plants infested, and by counting the leaves below the living dead pupae and pupae and 66 days to determine the outcome. 两个级别时间的结果在表A中概括。 The results are summarized in the two-level time Table A.

表A通过用化合物208的组合物涂覆棉籽而防治银叶粉虱 Table A Compound 208 by using the composition is coated cottonseed and prevention silverleaf whitefly

该试验表明本发明的种子涂层可以在播种后超过9周保护棉花植物免受同翅目害虫银叶粉虱的侵害。 The tests showed that the seed coating of the present invention may be more than nine weeks after sowing cotton to protect plants from pests Homopteran silverleaf whitefly damage.

试验B将如实施例E描述的方法制备的来自标称1％、标称2％和标称3％浓度的用化合物208的组合物涂覆的棉籽和用作对照的未经处理的种子种植在10-cm的无菌黄樟土罐中，并在25℃下16小时光照和8小时黑暗和50％相对湿度的生长箱中生长。 Test B The method described in Example E was prepared from the embodiment of nominal 1%, Nominal 2% and Nominal 3% concentration of the coating composition of Compound 208 Cottonseed planting the seeds and used as a control untreated in 10-cm pots sterile sassafras soil and grown at 25 ℃ under 16 h light and 8 h dark and 50% relative humidity in a growth chamber. 播种后14天，从一些植株上采集叶片，剪成3至4片，放置于生长箱中经覆盖的16孔(16-well)半透明塑料盘中，每孔放一片。 14 days after sowing, the plants collected from some blade, cut 3-4, placed in the growth chamber through 16 holes covered (16-well) translucent plastic dish, put a piece of each hole. 将烟草蚜虫(Heliothisvirescens)的二龄幼虫加到叶片上(1幼虫/孔，6-10幼虫/处理/叶片类型)，侵染后48小时和96小时测定害虫死亡率。 The tobacco budworm (Heliothisvirescens) second instar larvae was added to the blade (1 larva / well, 6-10 larvae / treatment / leaf type), 48 hours and 96 hours after infection, pest mortality was measured. 播种64天后从其它植物采集叶片，剪成3-4片，放置于生长箱中经覆盖的16孔半透明塑料盘中，每孔放一片。 64 days after sowing collected from leaves of other plants, cut into 3-4 pieces, placed in a growth chamber covered by a translucent plastic trays 16 holes, each hole put one. 将烟草蚜虫的二龄幼虫加到叶片上(1幼虫/孔，6-16幼虫/处理/叶片位置)，侵染后72小时和96小时测定害虫死亡率。 Second instar larvae of the tobacco budworm is applied to the blade (1 larva / well, 6-16 larvae / treatment / leaf location), 72 hours and 96 hours after infection, pest mortality was measured. 结果概括于表B1和B2中。 The results are summarized in Tables B1 and B2.

表B1通过用化合物208的组合物涂覆棉籽在播种后14天防治烟草蚜虫 Table B1 by compound composition is coated cottonseed 208 in 14 days after sowing tobacco prevention and control aphids

表B2通过用化合物208的组合物涂覆棉籽在播种后64天防治烟草蚜虫 Table B2 compound 208 by coating compositions cottonseed at 64 days after planting tobacco prevention and control aphids

*棉花植株上剪下叶片的位置。 * Cut the leaves on cotton plants location.

该试验表明，本发明的种子涂层可以保护棉花植物免受鳞翅目害虫烟草蚜虫的侵害超过播种后9周。 The experiment showed that the seed coating of the present invention can protect cotton plants from 9 weeks after the lepidopteran pest tobacco budworm than against sowing.

试验C将如实施例E所述制备的用化合物208处理的棉籽(标称3％批)和如实施例G所述制备的用化合物276、486和502处理的棉籽，以及用作对照的未经处理的种子种植在无菌黄樟土或黑色石首鱼土(Drummer soil)罐中。 Cottonseed (Nominal 3% batch) treated with compounds 208 Test C to E prepared as described in Example cottonseed treated with compounds 276,486 and 502 as prepared in Example G and a, and is not used as a control The treated seeds were planted in sterile sassafras soil or black kingfish soil (Drummer soil) tank. 植物在温室中生长，当它们开始发芽(方形)时，取样。 Plants grown in the greenhouse, when they begin to sprout (square), the sampling. 从第二节点的叶和大于15cm2的末端叶取样(植物约有5片叶)。 From the second node is greater than the end of the leaves and leaf sampling 15cm2 (plant about 5 leaves). 将来自各植株的经修剪的叶剪成4片，将各片置于具有一只烟草蚜虫二龄幼虫的孔中。 The plants were trimmed from each leaf cut 4, each of the slices placed in the wells with one second instar tobacco budworm larvae in. 取样后96小时记录幼虫死亡率。 96 hours after sampling larval mortality was recorded.

表C摄食在两种土壤类型中生长的经种子处理的叶的幼虫死亡率 Table C intake and growth in both soil types by seed treatment leaves larval mortality

试验D将如实施例F所述制备的用化合物208、484、486、502、509和515处理的玉米种子种植在黄樟土罐中。 Test D as described in Example F was prepared using the compound 208,484,486,502,509 and 515 corn seed treatment were planted in sassafras soil tank. 植株在温室中生长至轮生体高度(第9片叶)，用25只草地粘虫(一龄幼虫)侵染轮生体。 Plants grown in the greenhouse to whorl height (9th leaf), with 25 S.frugiperda (first instar larvae) infested whorls. 侵染后六天，记录与摄食相关的植株损伤。 Six days after infection, feeding records related to plant damage. 植株损害以0-100％评定(0表示未摄食)。 Assess the damage to plants from 0-100% (0 means no feeding).

表D在经不同种子处理的玉米植株上幼虫取食引起的植株损伤百分比 Table D Percentage plant damage on corn plants treated with different seed treatment caused larvae

试验E将如实施例H所述制备的以五级(标称1.75％、1.09％、0.58％、0.29％和0.15％)用化合物502处理的玉米种子种植在邻近Newark，DE和Donna，TX的农田中。 Test E The prepared as described in Example H to five (nominally 1.75%, 1.09%, 0.58%, 0.29% and 0.15%) planted with maize seeds treated compound 502 in adjacent Newark, DE and Donna, TX of farmland. 当植株生长的第5片叶至少10cm长时，将其剪下。 When the plants grow at least 5 leaves 10cm long, will it cut. 从至少16株植物每级取一片经修剪的叶，并置于具有一只二龄草地粘虫幼虫的孔中。 At least 16 plants from each grade to take a leaf trimmed and placed with a S.frugiperda second instar larvae in a hole. 侵染后72小时记录幼虫死亡率。 72 hours after infection larval mortality records.

测量Donna位点的玉米植株以确定植株生长。 Donna measurement sites to determine the plants grow corn plants. 将叶片叠近管中，记录管中由地面至叶片最顶端的高度。 The blade stack near tube, the tube from the ground to the recording top of the blade height.

表E1在用化合物502处理的种子的玉米的第5片叶上摄食引起的幼虫死亡率 Larval mortality Table E1 in the seeds treated with Compound 502 Corn leaf feeding caused by the fifth

表E2在Donna，TX用化合物502处理种子的玉米的植株高度 Table E2 in Donna, TX 502 seeds treated with a compound of corn plant height

从表E2可以看出，在该试验中用化合物502处理似乎促进植株生长。 As can be seen from Table E2, with the test compound (502) seems to promote plant growth.