哌嗪衍生物及其在防治害虫中的用途 Piperazine derivatives and their use in controlling pests

[0001] 本申请是发明名称为“哌嗪衍生物及其在防治害虫中的用途”的中国发明专利申请N0.200580021850.9的分案申请，其申请日是2005年05月12日，优先权日是2004年05月28日。 [0001] This application is a divisional application Title Chinese invention patent applications N0.200580021850.9 is "piperazine derivatives and their use in controlling pests", the filing date is May 12, 2005, the priority date It is May 28, 2004.

[0002] 本发明涉及哌嗪衍生物，制备它们的方法，包含它们的杀昆虫、杀螨虫、杀软体动物和杀线虫的组合物以及使用它们杀灭和防治昆虫、螨虫、软体动物和线虫的方法。 [0002] The present invention relates to piperazine derivatives, their preparation, including their insecticidal, acaricidal, molluscicidal and nematicidal compositions and use them to kill and control insects, mites, molluscs and nematodes Methods.

[0003] 例如在US331845中公开了哌嗪衍生物具有抗原虫(antiprotazoal)特性以及在EP103464中公开了嘧啶基哌嗪化合物具有杀菌特性。 [0003] In the example disclosed in US331845 piperazine derivatives having antiprotozoal (antiprotazoal) discloses the characteristics and pyrimidinyl piperazine compound having fungicidal properties are in EP103464.

[0004] 现在令人惊奇地发现一些哌嗪具有杀昆虫特性。 [0004] It has now surprisingly been found that some of the piperazine has insecticidal properties.

[0005] 因此本发明提供了一种杀灭和防治昆虫、螨虫、线虫或软体动物的方法，其包括对害虫、害虫的栖息地或易受害虫侵害的植物施用杀昆虫、杀螨、杀线虫或杀软体动物的有效量的式(I)化合物或其盐或N-氧化物: [0005] The present invention therefore provides a killing and controlling insects, mites, nematodes or molluscs which comprises insects, pests or habitat of plants susceptible to pests applying insecticides, nematicidally or molluscicidally effective amount of a Formula (I) or a salt thereof or N- oxide:

[0006] [0006]

[0007] Y是单键、C=0、C=S或S(O)ni，其中m是0、1或2 ;所述环 [0007] Y is a single bond, C = 0, C = S or S (O) ni, wherein m is 0, 1 or 2; the ring

[0008] [0008]

[0009] 是6元芳环或是5或6元杂芳环； [0009] 6-membered aromatic ring or a 5- or 6-membered heterocyclic aromatic ring;

[0010] R1是氢、任选取代的烷基、任选取代的烷氧羰基、任选取代的烷基羰基、氨基羰基、任选取代的烷基氨基羰基、任选取代的二烷基氨基羰基、任选取代的芳基、任选取代的杂芳基、任选取代的烷氧基、任选取代的芳氧基、任选取代的杂芳氧基、任选取代的杂环氧基、氰基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的环烯基、甲酰基、任选取代的杂环基、任选取代的烷硫基、NO或NR13R14,其中R13和R14独立地是氢、C0R15、任选取代的烷基、任选取代的芳基、任选取代的杂芳基、任选取代的杂环基或R13和R14与它们所连接N原子一起形成-N=C (R16) -NR17R18基团，或R13和R14与它们所相连的N原子一起形成五、六或七元杂环，其中所述杂环可含有一个或两个进一步选自0、N、或S的杂原子并且其可任选被一个或两个C^6烷基取代；R15是H、任选取代的烷基、任选取代的烷氧基、任选取代的芳基、任选取代的芳氧基、任选取代的杂芳基、任选取代的杂芳氧基或NR19R2° ;R16、R17和R18各自独立地是H或低级烷基；R19和R2tl独立地是任选取代的烷基、任选取代的芳基或者任选取代的杂芳基；[0011] R2是H、羟基、任选取代的烷氧基或者任选取代的烷基；或者R1和R2与基团Y和N一起形成5-或6-元杂环，所述杂环可任选含有一个进一步选自O、N或S的杂原子并且其可任选被Cy烷基、CV4卤代烷基或卤素取代。 [0010] R1 is hydrogen, optionally substituted alkyl, optionally substituted alkoxycarbonyl, optionally substituted alkylcarbonyl, aminocarbonyl, optionally substituted alkylaminocarbonyl, optionally substituted dialkylamino carbonyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocyclyloxy , a cyano group, an optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, formyl, optionally substituted heterocyclyl, optionally substituted alkoxy alkylthio, NO or NR13R14, wherein R13 and R14 are independently hydrogen, C0R15, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl or R13 and R14 as N atom to which they are connected together to form -N = C (R16) -NR17R18 group, or R13 and R14 with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring, wherein said heterocyclic ring may contain one or two further selected from 0, N, or S heteroatom and which may be optionally substituted with one or two C ^ 6 alkyl; R15 is H, optionally substituted alkyl, optionally substituted alkoxy , optionally substituted aryl, optionally substituted aryl group, optionally substituted heteroaryl, optionally substituted heteroaryloxy or NR19R2 °; R16, R17 and R18 are each independently H or lower alkyl group; R19 and R2tl are independently optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; [0011] R2 is H, hydroxy, optionally substituted alkoxy or optionally substituted alkyl group; or R1 and R2 groups Y and N together form a 5- or 6-membered heterocyclic ring, the heterocyclic ring may optionally contain a further selected from O, N or S heteroatoms and which may optionally Cy is alkyl, CV4 haloalkyl or halogen.

[0012] R4各自独立地为卤素、硝基、氰基、任选取代的Ci_8烷基、任选取代的C2_6烯基、任选取代的C2_6炔基、任选取代的烧氧擬基、任选取代的烷基擬基、任选取代的烷基氣基擬基、任选取代的二烷基氨基羰基、任选取代的C3_7环烷基、任选取代的芳基、任选取代的杂芳基、任选取代的杂环基、任选取代的烷氧基、任选取代的芳氧基、任选取代的杂芳氧基、任选取代的烷硫基或R21R22N,其中R21和R22独立地是氢、Ci_8烷基、C3_7环烷基、C3_6烯基、C3_6炔基、C3_7环烷基(C1J烷基、C2_6卤代烷基、C^6烷氧基(CV6)烷基、C^6烷氧羰基或者R21和R22与它们所相连的N原子一起形成五、六或七元杂环，所述杂环可含有一个或两个进一步选自O、N、或S的杂原子并且其可任选被一个或两个CV6烷基取代，或2个相邻基团R4与它们所相连的碳原子一起形成4、5、6或7元碳环或杂环，所述碳环或杂环可任选被卤素取代；n是0、1、2、3 或4。 [0012] R4 is independently halogen, nitro, cyano, optionally substituted Ci_8 alkyl, optionally substituted C2_6 alkenyl, optionally substituted C2_6 alkynyl, optionally substituted burn oxygen intends group, any It intends an alkyl group optionally substituted, an optionally substituted alkyl group quasi gas-yl, optionally substituted dialkylaminocarbonyl group, an optionally substituted C3_7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl aryl, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio or R21R22N, wherein R21 and R22 are independently hydrogen, Ci_8 alkyl, C3_7 cycloalkyl, C3_6 alkenyl, C3_6 alkynyl, C3_7 cycloalkyl (C1J alkyl, C2_6 haloalkyl, C ^ 6 alkoxy (CV6) alkyl, C ^ 6 alkoxycarbonyl, or R21 and R22 with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring, the heterocyclic ring may further contain one or two selected from O, N, or S heteroatom and which may be optionally substituted with one or two substituents CV6 alkyl, or 2 adjacent groups R4 together with the carbon atom to which they are attached form a 5, 6 or 7-membered carbocyclic or heterocyclic ring, said carbocyclic or heterocyclic ring It may optionally be substituted by halogen; n is 0,1,2,3 or 4.

[0013] R8是任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的环烷基、任选取代的芳基、任选取代的烷氧基、任选取代的芳氧基、任选取代的烷氧羰基、任选取代的烷基擬基或任选取代的烯基擬基； [0013] R8 is an optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted alkoxy, either optionally substituted aryloxy, optionally substituted alkoxycarbonyl, an optionally substituted alkyl group or an optionally substituted Quasi alkenyl group Quasi;

[0014] Ra各自独立地是卤素、羟基、氰基、任选取代的Ci_8烷基、任选取代的C2_6烯基、任选取代的C2_6炔基、任选取代的烧氧擬基、任选取代的烷基擬基、任选取代的烷基氣基擬基、任选取代的二烷基氨基羰基、任选取代的C3_7环烷基、任选取代的芳基、任选取代的杂芳基、任选取代的杂环基、任选取代的烷氧基、任选取代的芳氧基、任选取代的杂芳氧基、任选取代的烷硫基、任选取代的芳硫基或R23R24N,其中R23和R24独立地是氢、Ci_8烷基、C3_7环烷基、C3-6烯基、C3_6炔基、C3_7环烷基(Cu)烷基、C2_6卤代烷基、C^6烷氧基(Cu)烷基、C1^烧氧羰基或R23和R24和与它们所相连的N原子一起形成五、六或七元杂环，所述杂环可含有一或二个进一步选自O、N或S的杂原子并且其可任选被一个或两个(；_6烷基取代，或与同一个碳原子相连的两个Ra基团是=0、=S、=NRb, =CRcRd,其中Rb、Re和Rd独立地是H或任选取代的烷基$是0、1、2、3、或4。 [0014] Ra is independently halo, hydroxy, cyano, optionally substituted Ci_8 alkyl, optionally substituted C2_6 alkenyl, optionally substituted C2_6 alkynyl, optionally substituted burning oxygen quasi-yl, optionally Quasi substituted alkyl group, an optionally substituted alkyl group quasi gas-yl, optionally substituted dialkylaminocarbonyl group, an optionally substituted C3_7 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl group, optionally substituted heterocyclyl, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted alkylthio, optionally substituted arylthio group or R23R24N, wherein R23 and R24 are independently hydrogen, Ci_8 alkyl, C3_7 cycloalkyl, C3-6 alkenyl, C3_6 alkynyl, C3_7 cycloalkyl (Cu) alkyl, C2_6 haloalkyl, C ^ 6 alkoxy yl (Cu) alkyl, C1 ^ burning oxycarbonyl group or R23 and R24 and the N atom to which they are attached form a five, six or seven-membered heterocyclic ring, the heterocyclic ring may further contain one or two selected from O, N or S heteroatom and which may be optionally substituted with one or two (; _6 alkyl, or with a carbon atom with two Ra groups are = 0, = S, = NRb, = CRcRd, wherein Rb, Re and Rd are independently H or optionally substituted alkyl Yes 0,1,2,3, or 4.

[0015] 式(I)化合物可以各种几何或光学异构体或互变异构形式存在。 Compound [0015] of formula (I) can be various geometric or optical isomers or tautomeric forms. 本发明涵盖了所有的这些异构体、互变异构体和它们以各种比例的混合物以及同位素的形式例如氘代的化合物。 The present invention encompasses all of these isomers, tautomers compounds and their mixtures and in the form of various proportions of isotopes such as deuterium generation.

[0016] 单独的烷基或作为大基团(例如烷氧基、烧氧擬基、烷基擬基、烷基氣基擬基、_.烧基氨基羰基)的一部分的烷基可以各自是直链或支链的，例如是甲基、乙基、正丙基、正丁基、正戍基、正己基、异丙基；正丁基、仲丁基、异丁基、特丁基或者新戍基。 [0016] alone or as large alkyl groups (e.g., alkoxy, oxo burning intended group, an alkyl group proposed, an alkyl group proposed gas-based, _. Burned yl aminocarbonyl) alkyl portion may each be straight-chain or branched, e.g. methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, isopropyl; n-butyl, sec-butyl, isobutyl, t-butyl, or The new garrison base. 合适的烷基是C1-C12烷基，但优选C1-Cltl、更优选C1-C8、甚至更优选C1-C6和最优选C1-C4的烷基。 Suitable alkyl groups are C1-C12 alkyl, but preferably C1-Cltl, more preferably C1-C8, even more preferably C1-C6 and most preferably C1-C4 alkyl group.

[0017] 如果存在，烷基部分(单独或作为大基团例如烷氧基、烧氧擬基、烷基擬基、烷基氣基羰基、二烷基氨基羰基的一部分)上任选的取代基包括选自卤素、硝基、氰基、ncs-、c3_7环烷基(其任选被CV6烷基或卤素取代)、c5_7环烯基(其任选被Cu烷基或卤素取代)、羟基、Cp1(!烷氧基、(Cho)烷氧基(C1-KI)烷氧基、二(。卜4)烷基甲硅烷(C^6)烷氧基、Cp6烧氧擬基(C1,)烷氧基、C1,卤代烷氧基、芳基(Cy)烷氧基(其中芳基任选被取代)、C3_7环烷基氧基(其中环烷基任选被Cu烷基或卤素取代)、C2_10稀氧基、C2_1(l块氧基、SH、C1,烧硫基、C1-J0卤代烧硫基、芳基(CV4)烧硫基(其中芳基是任选被取代的)、C3_7环烷基硫基(其中环烧基任选被Cu烷基或卤素取代)、二(Cu)烷基甲娃烷基(CV6)烧硫基、芳硫基(其中芳基是任选被取代的)、C1^6烷基磺酰基、C1^6卤代烷基磺酰基、C1^6烷基亚磺酰基、C1^6卤代烷基亚磺酰基、芳基磺酰基(其中芳基可以是任选被取代的)、三(Cm)烷基甲硅烷基、芳基二(CV4)烷基甲硅烷基、(Cu)烷基二芳基甲硅烷基、三芳基甲硅烷基、C1,烷基羰基、HO2C, C1,烷氧羰基、氨基羰基、CV6烷基氨基羰基、二((V6烷基)氨基羰基、N-(C^烷基)-N-(C^烷氧基)氨基羰基、Ch6烷基羰氧基、芳基羰氧基(其中芳基是任选被取代的)、二(CV6)烷基氨基羰基氧基、肟例如=NO烷基、=NO卤代烷基和=NO芳基(其是任选被取代的)、芳基(其是任选被取代的)、杂芳基(其是任选被取代的)、杂环基(其是任选被Cm烷基或卤素取代的)、芳氧基(其中芳基是任选被取代的)、杂芳氧基(其中杂芳基是任选被取代的)、杂环氧基(其中杂环基任选被Cu烷基或卤素取代)、氣基、Cu烷基氣基、_.(CV6)烷基氣基、Cu烷基擬基氣基、N-(CV6)烷基羰基-N-(CV6)烷基氨基、c2_6烯基羰基、C2_6炔基羰基、C3_6烯氧基羰基、C3_6炔氧基羰基、芳氧羰基(其中芳基任选被取代)和芳基羰基(其中芳基任选被取代)中的一种或多种。 [0017] If present, the alkyl moiety (either alone or as large groups such as alkoxy, oxygen burning intended group, an alkyl group intends, gas-alkyl-carbonyl, part dialkylaminocarbonyl group) optionally substituted on the selected from the group comprising halogen, nitro, cyano, ncs-, c3_7 cycloalkyl (optionally substituted with alkyl or halogen CV6), c5_7 cycloalkenyl (which is optionally substituted Cu alkyl or halogen), hydroxy , Cp1 (! alkoxy, (Cho) alkoxy (C1-KI) alkoxy, di (. Bu 4) alkylsilyl (C ^ 6) alkoxy, Cp6 burning oxygen quasi-yl (C1, ) alkoxy, C1, haloalkoxy, aryl (Cy) alkoxy (wherein the aryl group is optionally substituted), C3_7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with alkyl or halogen substituted Cu) , C2_10 dilute group, C2_1 (l block group, SH, C1, burning thio, C1-J0 haloalkyl burn group, an aryl group (CV4) thio burn (where the aryl group is optionally substituted), C3_7 cycloalkyl group (wherein the cycloalkyl group is optionally substituted with burning Cu alkyl or halogen), di (Cu) alkylsilyl group Wa (CV6) burning thio, arylthio (where the aryl group is optionally substituted with substituted), C1 ^ 6 alkylsulfonyl group, C1 ^ 6 haloalkylsulfonyl, C1 ^ 6 alkylsulfinyl, C1 ^ 6 haloalkoxy alkylsulfinyl, arylsulfonyl (where the aryl group can be optionally substituted), tris (Cm) alkylsilyl, diaryl (CV4) alkylsilyl, (Cu) alkyl diaryl silyl, triaryl silyl, C1, alkylcarbonyl , HO2C, C1, alkoxycarbonyl, aminocarbonyl, CV6 alkylaminocarbonyl, di ((V6 alkyl) aminocarbonyl, N- (C ^ alkyl) -N- (C ^ alkoxy) aminocarbonyl, Ch6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di (CV6) alkylaminocarbonyl group, oxime such as = NO-alkyl, = NO = NO haloalkyl and aryl (which is optionally substituted), aryl (which is optionally substituted), heteroaryl (which is optionally substituted), a heterocyclic group (which is optionally substituted by alkyl or halogen Cm a), aryloxy (where the aryl group is optionally substituted), heteroaryloxy (wherein the heteroaryl group is optionally substituted), heterocyclic groups (wherein heterocyclyl is optionally substituted Cu alkyl or halogen), gas-based, Cu alkyl group air, _. (CV6) alkyl group gas, Cu alkyl group intends gas group, N- (CV6) alkylcarbonyl -N- (CV6) alkylamino, c2_6 alkenylcarbonyl group, C2_6 alkynyl carbonyl, C3_6 alkenyloxy carbonyl, C3_6 alkynyl group, a carbonyl group, an aryloxycarbonyl group (wherein the aryl group is optionally substituted) and arylcarbonyl (where the aryl group is optionally substituted) in a or more.

[0018] 烯基和炔基部分可以是直链或支链形式，并且烯基部分可以适当地是(E)-或(Z)-构型。 [0018] Alkenyl and alkynyl moieties can be straight-chain or branched-chain, and the alkenyl moieties may suitably be (E) - or (Z) - configuration. 例如为乙烯基、烯丙基和炔丙基。 For example, vinyl, allyl and propargyl.

[0019] 如果存在，烯基或炔基上可带有任意取代基，这些取代基包括上面烷基部分所给出的那些任意取代基。 [0019] When present, the alkenyl or alkynyl group may be optionally substituted with a group, any of these substituents include those given above, the alkyl portion of the substituent.

[0020] 在本说明书范围内酰基是任选取代的CV6烷基羰基(例如乙酰基)、任选取代的c2_6烯基羰基、任选取代的C2_6炔基羰基、任选取代的芳羰基(例如苯甲酰基)或任选取代的杂芳擬基。 [0020] In the context of this specification acyl is optionally substituted CV6 alkylcarbonyl (e.g. acetyl), optionally substituted c2_6 alkenyl carbonyl, optionally substituted C2_6 alkynyl carbonyl, optionally substituted arylcarbonyl (e.g. benzoyl) or optionally substituted heteroaryl group proposed.

[0021] 卤素是氟、氯、溴或碘。 [0021] Halogen is fluorine, chlorine, bromine or iodine.

[0022] 卤代烷基是被一个或多个相同或不同的卤素原子取代的烷基，例如CF3、CF2Cl,CF3CH2 或CHF2CH2。 [0022] haloalkyl is substituted with one or more identical or different halogen atoms, alkyl groups, for example CF3, CF2Cl, CF3CH2 or CHF2CH2.

[0023] 在本申请说明书范围内术语“芳基”、“芳环”和“芳环系”是指可以是单_、双-或三环的环系。 [0023] In the present specification within the scope of the term "aryl", "aromatic ring" and "aromatic ring system" is one that can be _ single, double - or tricyclic ring system. 这类环的例子包括苯基、萘基、蒽基、茚基或菲啶基。 Examples of such rings include phenyl, naphthyl, anthryl, indenyl, or phenanthridinyl. 芳基优选是苯基。 Aryl is preferably phenyl. 另外，术语“杂芳基”、“杂芳环”或“杂芳环”或“杂芳环系”是指含有至少一个杂原子并且由具有单环或两个或多个稠环组成的芳环系。 Further, the term "heteroaryl", "heteroaromatic ring" or "heteroaromatic ring" or "heteroaromatic ring system" refers to containing at least one hetero atom and having a single ring or two or more fused aromatic rings ring system. 优选的是，单环可含至多三个和双环体系至多四个杂原子，所述杂原子优选选自氮、氧和硫。 Preferably, a monocyclic ring may contain up to three and bicyclic systems up to four heteroatoms, preferably a heteroatom selected from nitrogen, oxygen and sulfur. 这类基团的例子包括呋喃基、噻吩基、吡咯基、吡唑基、咪唑基、1，2，3-三唑基、1，2，4-三唑基、噁唑基、异噁唑基、噻唑基、异噻唑基、1，2，3-噁二唑基、I, 2，4-噁二唑基、I, 3，4-噁二唑基、I, 2，5-噁二唑基、I, 2，3-噻二唑基、I, 2，4-噻二唑基、1，3，4-噻二唑、1，2，5-噻二唑、吡啶基、嘧啶基、哒嗪基、吡嗪基、1，2，3-三嗪基、1，2，4-三嗪基、1，3，5-三嗪基、苯并呋喃基、苯并异呋喃基、苯并噻吩噻吩基、苯并异噻吩基、吲哚基、异氮茚基、吲唑基、苯并噻唑基、苯并异噻唑基、苯并噁唑基、苯并异噁唑基、苯并咪唑基、2，I, 3-苯并噁二唑、喹啉基、异喹啉基、噌啉基、酞嗪基、喹唑啉基、喹喔啉基、萘啶基、苯并三嗪基、嘌呤基、蝶啶基和中氮茚基。 Examples of such groups include the furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazole, 1,2,4-triazole, oxazolyl, isoxazolyl group, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, I, 2,4- oxadiazolyl, I, 3,4- oxadiazolyl, I, 2,5- oxadiazol oxazolyl, I, 2,3- thiadiazolyl, I, 2,4- thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyrimidinyl , pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzofuranyl, benzo furanyl isobutyl, benzothiophene thienyl, benzoisoxazole thienyl, indolyl, iso-indolizinyl, indazolyl, benzothiazolyl, benzisothiazole group, benzoxazolyl, benzisoxazolyl, benzene and imidazolyl, 2, I, 3- benzo oxadiazole, quinolinyl, isoquinolinyl, cinnolinyl, phthalazine group, quinazolinyl, quinoxalinyl, naphthyridinyl, benzotriazole triazine, purinyl, pteridinyl and indolizinyl. 优选的杂芳基的例子包括吡啶基、嘧啶基、三嗪基、噻吩基、呋喃基、噁唑基、异噁唑基、2，I, 3-苯并噁二唑基和噻唑基。 Examples of preferred heteroaryl groups include pyridyl, pyrimidinyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl, 2, I, 3- benzo-oxadiazolyl and thiazolyl.

[0024] 术语杂环和杂环基是指含有至多10个原子的包括一个或多个(优选一个或两个)选自0、S和N的杂原子的非芳族环。 [0024] The term heterocyclic refers to a heterocyclic group of up to 10 atoms including one or more (preferably one or two) selected from 0, S and non-aromatic ring of the N heteroatom. 这类环的例子包括1，3-二氧戊烷、四氢呋喃和吗啉。 Examples of such rings include 1,3-dioxolane, tetrahydrofuran and morpholine. [0025] 如果存在，杂环基上可带有任意取代基，这些取代基包括Cp6烷基和Cu卤代烷基以及上面对烷基部分所给出的那些任意取代基。 [0025] if present, may be heterocyclic group optionally having a substituent, these substituents include Cu Cp6 alkyl and haloalkyl, and those on the face of any given portion of the alkyl substituents.

[0026] 环烷基包括环丙基、环戊基和环己基。 [0026] Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

[0027] 环烯基包括环戊烯基和环己烯基。 [0027] cycloalkenyl groups include cyclopentenyl and cyclohexenyl.

[0028] 如果存在，环烷基或环烯基上可带有任意取代基，这些取代基包括Cu烷基以及上面对烷基部分所给出的那些任意取代基。 [0028] If there is, the cycloalkyl or cycloalkenyl group which may have optionally a substituent, these substituents include an alkyl group, and Cu on the face of those given in the alkyl portion of any substituent.

[0029] 碳环包括芳基、环烷基和环烯基。 [0029] include carbocyclic aryl, cycloalkyl and cycloalkenyl. 如果存在，芳基或杂芳基上任选的取代基独立地选自卤素、硝基、氰基、NCS-、C1^6烷基、C1^卤代烷基、CV6烷氧基(Cu)烷基、c2_6烯基、c2_6卤代烯基、C2_6炔基、C3_7环烷基(其任选被Cu烷基或卤素取代)、C5_7环烯基(任选被Cu烧基或卤素取代)、羟基、C1,烷氧基、C1,烷氧基(C1,)烷氧基、二(Cu)烷基甲娃烷基(Cp6)烷氧基、CV6烧氧擬基(C1,)烷氧基、C1,卤代烷氧基、芳基(CV4)烷氧基(其中芳基任选被C1-S烷基或卤素取代)、C3_7环烷基氧基(其中环烷基任选被Cu烷基或卤素取代)、C2_10稀氧基、C2_10块氧基、SH> C1,烧硫基、C1^0卤代烧硫基、芳基(CV4)烧硫基、C3_7环烷基硫基(其中环烷基任选被Cu烷基或卤素取代)、二(CV4)烷基甲娃烷基(CV6)烧硫基、芳硫基、Cu烧基磺酰基、(V6卤代烷基磺酰基、Cu烷基亚磺酰基、CV6卤代烷基亚磺酰基、芳基磺酰基、三((V4)烷基甲硅烷基、芳基二(CV4)烷基甲硅烷基、(CV4)烷基二芳基甲硅烷基、三芳基甲硅烷基、C1,烷基羰基、HO2CC1,烷氧羰基、氨基羰基、Ch6烷基氨基羰基、二(C^6烷基)氨基羰基、N-(Cu烷基)-N-((V3烷氧基)氨基羰基、C1^6烷基羰氧基、芳基羰氧基、二(CV6)烷基氨基羰基氧基、芳基(其任选被Cu烷基或卤素取代)、杂芳基(其任选被Cu烷基或卤素取代)、杂环基(其任选被CV6烷基或卤素取代)、芳氧基(其任选被Cu烷基或卤素取代)、杂芳氧基(其任选被Cu烷基或卤素取代)、杂环氧基(其中杂环基任选被CV6烷基或卤素取代)、氨基、C1^6烷基氨基、二(CV6)烷基氨基、CV6烷基羰基氨基、N-(Cp6)烷基羰基-N-(Cp6)烷基氨基、芳基羰基(其中芳基任选被CV6烷基或卤素取代)或者芳基或杂芳基上两相邻位置可成环形成5、6或7元碳环或杂环，所述`碳环或杂环任选被卤素或Cu烷基取代。更进一步的芳基或杂芳基的取代基包括芳基羰基氨基(其中芳基被(V6烷基或卤素取代)、(C1^6)烷氧羰基氨基(Cu)烷氧羰基-N-(CV6)烷基氨基、芳氧基羰基氨基(其中芳基被Ch6烷基或卤素取代)、芳氧羰基-N- (CV6)烷基氨基(其中芳基被Cu烷基或卤素取代)、烷基磺酰氨基(其中芳基被Cu烷基或卤素取代)、芳基磺酰基-N-(Ch6)烷基氨基(其中芳基被Cu烷基或卤素取代)、芳基-N- (CV6)烷基氨基(其中芳基被Ch6烷基或卤素取代)、芳基氨基(其中芳基被(V6烷基或卤素取代)、杂芳基氨基(其中杂芳基被Cu烷基或卤素取代)、杂环氨基(其中杂环基被Cu烷基或卤素取代)、氣基擬基氣基、CV6烷基氣基擬基氣基、_.(C^6)烷基氣基擬基氨基、芳基氨基羰基氨基(其中芳基被Ch6烷基或卤素取代)、芳基-N- (C1^6)烷基氨基羰基氨基(其中芳基被Ch6烷基或卤素取代XCh烷基氨基羰基-N-(U烷基氨基、二(U烷基氨基羰基-N-(C1J烷基氨基、芳基氨基羰基-N-(Ch)烷基氨基(其中芳基被CV6烷基或卤素取代)和芳基-N-(C1J烷基氨基羰基-N-(C1J烷基氨基(其中芳基被Cm烷基或卤素取代)。 If present, an aryl group or a heteroaryl group optionally substituted independently selected from halogen, nitro, cyano, NCS-, C1 ^ 6 alkyl, C1 ^ haloalkyl, CV6 alkoxy (Cu) alkyl , c2_6 alkenyl, c2_6 halogenated alkenyl, C2_6 alkynyl, C3_7 cycloalkyl (optionally substituted Cu alkyl or halogen), C5_7 cycloalkenyl group (optionally substituted by halo group or burn Cu), a hydroxyl group, C1, alkoxy, C1, alkoxy (C1,) alkoxy, di (Cu) alkylsilyl group Wa (Cp6) alkoxy, CV6 burning oxygen quasi-yl (C1,) alkoxy, C1 , haloalkoxy, aryl (CV4) alkoxy (wherein aryl is optionally substituted with C1-S alkyl or halogen), C3_7 cycloalkyloxy (where the cycloalkyl is optionally substituted with alkyl or halogen Cu ), C2_10 dilute group, C2_10 block group, SH> C1, burning thio, C1 ^ 0 haloalkyl group burn, an aryl group (CV4) burning thio, C3_7 cycloalkyl group (wherein the cycloalkyl either optionally substituted Cu alkyl or halogen), di (CV4) alkylsilyl group Wa (CV6) burning thio, arylthio, Cu burning sulfonyl, (V6 haloalkylsulfonyl, Cu alkylsulfinyl , CV6 haloalkyl alkylsulfinyl, arylsulfonyl, tris ((V4) alkylsilyl, diaryl (CV4) alkylsilyl, (CV4) alkyl diaryl silyl, triaryl silyl, C1, alkylcarbonyl, HO2CC1, alkoxycarbonyl, aminocarbonyl, Ch6 alkylaminocarbonyl, di (C ^ 6 alkyl) aminocarbonyl, N- (Cu alkyl) -N - ((V3 alkyl oxy) aminocarbonyl, C1 ^ 6 alkylcarbonyloxy, arylcarbonyloxy, di (CV6) alkylaminocarbonyl group, an aryl group (which is optionally substituted Cu alkyl or halogen), heteroaryl (Cu which is optionally substituted with alkyl or halogen), heterocyclyl (optionally substituted by alkyl or halogen CV6 substituted), aryloxy (optionally substituted Cu alkyl or halogen), heteroaryloxy ( Cu which is optionally substituted alkyl or halogen), heterocyclyloxy (where the heterocyclyl group is optionally substituted CV6 alkyl or halogen), amino, C1 ^ 6 alkylamino, di (CV6) alkylamino, CV6 On alkylcarbonylamino, N- (Cp6) alkylcarbonyl -N- (Cp6) alkylamino, arylcarbonyl (where the aryl group is optionally substituted CV6 alkyl or halogen), or an aryl or heteroaryl two phases ortho position can be formed into a ring 5, 6 or 7-membered carbocyclic or heterocyclic ring, said carbocyclic or heterocyclic ring is optionally 'substituted with halo or Cu alkyl. Further substituents for aryl or heteroaryl include aryl carbonyl amino group (wherein the aryl group is (V6 alkyl or halo-substituted), (C1 ^ 6) alkoxycarbonyl amino (Cu) alkoxycarbonyl -N- (CV6) alkylamino group, an aryloxycarbonyl amino group (wherein aryl alkyl groups or halo substituted Ch6), an aryloxycarbonyl group -N- (CV6) alkylamino (where the aryl group is substituted Cu alkyl or halogen), an alkylsulfonyl group (wherein the aryl group is an alkyl group or a halogen Cu substituted), an arylsulfonyl group -N- (Ch6) alkylamino (where the aryl group is substituted Cu alkyl or halogen), aryl -N- (CV6) alkylamino (where the aryl group is an alkyl group or a halogen Ch6 substituted), arylamino (where the aryl group is (V6 substituted alkyl or halogen), heteroaryl amino (where the heteroaryl is substituted Cu alkyl or halogen), a heterocyclic amino group (wherein the heterocyclic group is an alkyl group Cu or halogen), gas-gas-based group intends group, CV6 alkyl group quasi gas-gas-based group, _. (C ^ 6) alkyl group quasi gas-amino, arylaminocarbonyl amino group (wherein the aryl group is Ch6 or halo-substituted), aryl -N- (C1 ^ 6) alkylaminocarbonyl amino (wherein the aryl group is substituted with alkyl or halogen XCh Ch6 alkylaminocarbonyl -N- (U alkylamino, di (U group aminocarbonyl -N- (C1J alkylamino, arylamino carbonyl -N- (Ch) alkylamino (where the aryl group is substituted CV6 alkyl or halogen) and aryl -N- (C1J alkylaminocarbonyl group -N - (C1J alkylamino (where the aryl group is substituted with alkyl or halogen Cm).

[0030] 对苯基部分、杂环基和杂芳基被取代的情况，优选所述取代基独立地选自卤素、C1-S烷基、C1^卤代烷基、C^6烷氧基(Cp6)烷基、Cu烷氧基、C1^卤代烷氧基、C1^烧硫基、(V6卤代烷硫基、CV6烷基亚磺酰基、CV6卤代烷基亚磺酰基、C1^6烷基磺酰基、C1^6卤代烷基磺酰基、c2_6烯基、C2_6卤代烯基、C2_6炔基、C3_7环烷基、硝基、氰基、CO2H, C1^6烷基羰基、CV6烷氧羰基、R25R26N或R27R28NC(O)中的一种或多种；其中R25、R26、R27和R28独立地是氢或CV6烷基。进一步优选的取代基是芳基和杂芳基。 [0030] The phenyl moieties, heterocyclyl and heteroaryl group is substituted, the preferred substituents are independently selected from halogen, C1-S alkyl, C1 ^ haloalkyl, C ^ 6 alkoxy (Cp6 ) alkyl, Cu alkoxy, C1 ^ haloalkoxy, C1 ^ burning thio, (V6 haloalkylthio, CV6 alkylsulfinyl, CV6 haloalkyl alkylsulfinyl, C1 ^ 6 alkylsulfonyl group, C1 ^ 6 haloalkylsulfonyl, c2_6 alkenyl, C2_6 haloalkyl alkenyl, C2_6 alkynyl, C3_7 cycloalkyl, nitro, cyano, CO2H, C1 ^ 6 alkylcarbonyl, CV6 alkoxycarbonyl, R25R26N or R27R28NC ( O) in one or more; in which R25, R26, R27 and R28 are independently hydrogen or alkyl CV6 further preferred substituents are aryl and heteroaryl.

[0031] 卤代烯基是其中被一个或多个相同或不同的卤素原子取代的烯基。 [0031] haloalkenyl which is substituted by one or more identical or different halogen atoms, an alkenyl group.

[0032] 应理解的是二烷基氨基取代基包括那些与它们所相连的N原子一起形成五、六或七元杂环的二烷基，其中所述杂环可含有一个或两个进一步选自O、N或S的杂原子并且它可任选被一个或两个独立地选自(CV6)烷基的取代基取代。 [0032] It should be understood that dialkylamino substituents include those with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring together with dialkyl, wherein said heterocyclic ring may further contain one or two selected from Since O, N or S atom and which may optionally substituted with one or two independently selected (CV6) alkyl substituents. 如果杂环是通过N原子上的两个基团形成的，则所形成的环合适的是吡咯、哌啶、硫吗啉和吗啉，其中各自可被一个或两个独立地选自(C1J烷基的基团取代。 If the heterocyclic ring through two groups formed on the N atom, the ring formed is suitable pyrrole, piperidine, thiomorpholine and morpholine, each of which may be one or two independently selected (C1J substituted alkyl groups.

[0033] 优选烷基部分上任选取代的取代基包括选自卤素、硝基、氰基、HO2C, C1,烷氧基(其任选被C1,烷氧基取代)、芳基(Cu)烷氧基、C1^0烧硫基、C1,烧擬基、C1,烧氧擬基、(V6烷基氨基羰基、二(C^6烷基)氨基羰基、(C1J烷基羰基氧基、任选取代的苯基、杂芳基、芳氧基、芳基擬氧基、杂芳氧基、杂环基、杂环氧基、C3_7环烷基(其任选被(Cu)烷基或卤素取代)、C3_7环烷基氧基、C5_7环烯基、Cu烷基横酸基、Cu烷基亚横酸基、二(Cu)烷基甲娃烷基、三(Cu)烷基甲硅烷基(C1J烷氧基、芳基二(CV4)烷基甲硅烷基、(Cu)烷基二芳基甲娃烷基和二芳基甲娃烷基中的一种或多种。 [0033] Preferably the alkyl moiety is optionally substituted with substituents selected from the group comprising halogen, nitro, cyano, HO2C, C1, alkoxy (optionally substituted by C1, alkoxy), aryl (Cu) alkoxy, C1 ^ 0 burn thio, C1, burning quasi-yl, C1, burning oxygen quasi-yl, (V6 alkylaminocarbonyl, di (C ^ 6 alkyl) aminocarbonyl, (C1J alkylcarbonyloxy, optionally substituted phenyl, heteroaryl, aryloxy, aryl group proposed, heteroaryloxy, heterocyclyl, heterocyclyloxy, C3_7 cycloalkyl (optionally substituted by (Cu) alkyl or halogen-substituted), C3_7 cycloalkyl group, C5_7 cycloalkenyl, Cu cross acid alkyl group, Cu alkylsilylene cross acid group, a di (Cu) A baby alkyl group, three (Cu) alkylsilyl group (C1J alkoxy, aryl, di (CV4) alkylsilyl, the (Cu) alkyl diaryl A baby and diaryl alkyl group of one or more carboxylic baby.

[0034] 优选烯基或炔基上任选的取代基包括卤素、芳基和C3_7环烷基中的一种或多种。 The [0034] preferred alkenyl or alkynyl optional substituents include halogen, C3_7 cycloalkyl, aryl and one or more.

[0035] 优选杂环基任选的取代基是Cu烷基。 [0035] Preferably heterocyclyl is optionally substituted Cu alkyl group.

[0036] 优选环烷基任选的取代基包括卤素、氰基和CV3烷基。 [0036] cycloalkyl preferably optional substituents include halogen, cyano and alkyl CV3.

[0037] 优选环烯基任选的取代基包括Cu烷基、卤素和氰基。 [0037] Preferably cycloalkenyl Cu optional substituents include alkyl, halogen and cyano.

[0038] 基团T、Y、Ra、R1、R2、R4和R8在任一种组合中的优选基团如下所示。 [0038] group T, Y, Ra, R1, R2, R4 and R8 in any combination of preferred groups as shown below.

[0039] 优选Y是单键、C=O或C=S。 [0039] Preferably Y is a single bond, C = O or C = S.

[0040] 更优选Y是单键或C=O。 [0040] More preferably Y is a single bond or C = O.

[0041] 最优选Y是C=O。 [0041] Most preferably Y is C = O.

[0042] 优选R1是氧、C^6烷基、Cp6氛基烷基、C1^卤代烷基、C3_7环烷基(Cu)烷基、Cp6烷氧基(Cu)烷基、杂芳基(CV6)烷基(其中杂芳基可任选被卤素、硝基、氰基、Ch6烷基、CV6卤代烷基、(V6烷氧基、C^6卤代烷氧基、(；_6烷基磺酰基、(V6烷基亚磺酰基、C^6烷硫基、(V6烷氧基羰基、CV6烷基羰基氨基、芳基羰基取代，或杂芳环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、芳基(Cu)烷基(其中芳基可任选被卤素、硝基、氰基、C1^6烷基、C1^6卤代烷基、C1^6烷氧基、C1^6卤代烷氧基、CV6烷基磺酰基、C1^6烷基亚磺酰基、C1-S烧硫基、Cu烷氧基擬基、C^6烷基擬基氣基、芳基擬基取代，或芳基上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、C1^6烷基羰基氨基(Cu)烷基、芳基(其可任选被卤素、硝基、氰1基、C1^烷基、C^6卤代烷基、C1^烷氧基、C^6卤代烷氧基、C1^烷基横酸基、CV6烷基亚横酸基、Cu烧硫基、Cu烷氧基擬基、CV6烷基擬基氣基、芳基擬基取代，或芳基上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、杂芳基(其可任选被卤素、硝基、氛基、C1^烷基、C^6卤代烷基、C1^烷氧基、C^6卤代烷氧基、C1^烷基横酸基、CV6烷基亚横酸基、Cu烧硫基、Cu烷氧基擬基、CV6烷基擬基氣基、芳基擬基取代，或杂芳基上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、C1^6烷氧基、C1-S卤代烷氧基、苯氧基(其中苯基任选被卤素、C^4烷基、Cu烷氧基、Cu卤代烷基、C^4齒代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳氧基(任选被卤素、硝基、氰基、Cu烷基、Cp6卤代烷基、Cu烷氧基或Cu卤代烷氧基取代)、杂环氧基(任选被卤素、CV6烷基、CV6卤代烷基、Cu烷氧基或Cu卤代烷氧基取代)、氛基、C2_6烯基、C2_6炔基、C3_6环烧基、C5_7环烯基、杂环基(任选被卤素、硝基、氛基、C^6烷基、Cp6卤代烷基、C^6烷氧基或CV6卤代烷氧基取代)、C1^6烷硫基、Cu卤代烷硫基或NR13R14,其中R13和R14独立地是氢、C1^6烷基、CV6卤代烷基、Cu烷氧基(CV6)烷基、苯基(其可任选被卤素、Cu烷基、Cu烷氧基、Cp4卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基、二烷基氨基或Cy烷氧羰基取代)、苯基(Cu)烷基(其中苯基可任选被卤素、C^4烷基、CV4烷氧基、CV4卤代烷基、C^4卤代烧氧基、CN、NO2、芳基、杂芳基、氨基、二烷基氨基、CV6烷基磺酰基、CV6烷氧羰基取代，或苯环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、杂芳基(Cu)烷基(其中杂芳基可任选被卤素、硝基、氛基、C1^烷基、Cp6卤代烷基、C^6烷氧基、Cu卤代烷氧基、C1-S烷基横酸基、CV6烷基亚横酸基、Cu烧硫基、Cu烷氧基擬基、CV6烷基擬基氣基、芳基擬基取代，或杂芳环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)或杂芳基(其可任选被卤素、硝基、氰1基、C1^烷基、Cp6卤代烷基、C1^烷氧基或Cu卤代烷氧基、C^4烷氧基擬基、C^6烷基擬基氣基、苯氧基擬基氣基(其中苯基任选被卤素、Cu烷基、Cu烧氧基、Cy卤代烷基、CV4卤代烷氧基、cn、no2、芳基、杂芳基、氨基或二烷基氨基取代)、氨基、(V6烷基氨基或苯氨基(其中苯基任选被卤素、CV4烷基、Ci_4烷氧基、Ci_4卤代烷基、Ci_4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)取代)。 [0042] Preferably, R1 is oxygen, C ^ 6 alkyl, Cp6 atmosphere alkyl, C1 ^ haloalkyl, C3_7 cycloalkyl (Cu) alkyl, Cp6 alkoxy (Cu) alkyl, heteroaryl (CV6 ) alkyl (wherein the heteroaryl may be optionally substituted by halogen, nitro, cyano, Ch6 alkyl, CV6 haloalkyl, (V6 alkoxy, C ^ 6 haloalkoxy, (; _ 6 alkylsulfonyl, ( V6 alkylsulfinyl, C ^ 6 alkylthio, (V6 alkoxycarbonyl, CV6 alkylcarbonylamino group, a substituted arylcarbonyl group, or a heteroaromatic ring two adjacent positions may form a ring formed 5, 6 or 7 membered optionally substituted carbocyclic or heterocyclic halogen), aryl (Cu) alkyl (where the aryl group is optionally substituted by halogen, nitro, cyano, C1 ^ 6 alkyl, C1 ^ 6 haloalkyl, C1 ^ 6 alkoxy, C1 ^ 6 haloalkoxy, CV6 alkylsulfonyl, C1 ^ 6 alkylsulfinyl group, C1-S alkylthio burning, Cu quasi alkoxy group, C ^ 6 alkyl group intends gas group, a substituted aryl group intended, or two adjacent positions on the aryl group may be a 5, 6 or 7-membered ring formed optionally substituted by halogen carbocyclic or heterocyclic ring), C1 ^ 6 alkylcarbonylamino (Cu) alkyl group, an aryl group (which may be optionally substituted by halogen, nitro, a cyano group, C1 ^ alkyl, C ^ 6 haloalkyl, C1 ^ alkoxy, C ^ 6 haloalkoxy, C1 ^ alkyl acid groups cross- , CV6 alkylsilylene cross acid group, Cu burning sulfur, Cu alkyl group intends group, CV6 alkyl group proposed gas-based, quasi-substituted aryl, or two adjacent positions on the aryl group may form a ring form 5,6 optionally substituted by halogen or 7-membered carbocyclic or heterocyclic ring substituted), heteroaryl (which may be optionally substituted by halogen, nitro, atmosphere group, C1 ^ alkyl, C ^ 6 haloalkyl, C1 ^ alkoxy, C ^ 6 haloalkoxy, C1 ^ alkyl cross acid group, CV6 alkylsilylene cross acid group, Cu burning sulfur, Cu alkyl group intends group, CV6 alkyl group proposed gas-based, quasi-substituted aryl, or the heteroaryl two adjacent positions may form a ring formed by 5, 6 or 7-membered optionally halogen-substituted carbocyclic or heterocyclic), C1 ^ 6 alkoxy, C1-S haloalkoxy, phenoxy (wherein phenyl optionally substituted by halogen, C ^ 4 alkyl, Cu alkoxy, Cu haloalkyl, C ^ 4 alkoxy group tooth, CN, NO2, aryl, heteroaryl, amino or dialkylamino) , heteroaryloxy (optionally substituted by halogen, nitro, cyano, Cu alkyl, Cp6 haloalkyl, Cu Cu alkoxy or haloalkoxy group), a heterocyclic oxy group (optionally substituted by halogen, CV6 alkyl , CV6 haloalkyl, Cu Cu alkoxy or haloalkoxy group), group atmosphere, C2_6 alkenyl, C2_6 alkynyl, C3_6 cycloalkyl group burning, C5_7 cycloalkenyl, heterocyclyl (optionally substituted by halogen, nitro, atmosphere group, C ^ 6 alkyl, Cp6 haloalkyl, C ^ 6 alkoxy or haloalkoxy CV6 substituted), C1 ^ 6 alkylthio, Cu haloalkylthio or NR13R14, wherein R13 and R14 are independently hydrogen, C1 ^ 6 alkyl, CV6 haloalkyl, Cu alkoxy (CV6) alkyl, phenyl (which may be optionally substituted by halogen, Cu alkyl, Cu alkoxy, Cp4 haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino or alkoxycarbonyl group substituted Cy), phenyl (Cu) alkyl (wherein the phenyl group optionally substituted by halogen, C ^ 4 alkyl, CV4 alkyl group, CV4 haloalkyl, C ^ 4 haloalkoxy group burning, CN, NO2, aryl, heteroaryl, amino, dialkylamino, CV6 alkylsulfonyl, CV6 substituted alkoxycarbonyl group, or a benzene ring Two adjacent positions may form a ring formed 6 or 7 membered carbocyclic or heterocyclic ring optionally substituted by halo-substituted), heteroaryl (Cu) alkyl (wherein the heteroaryl may be optionally substituted by halogen, nitro, atmosphere group, C1 ^ alkyl, Cp6 haloalkyl, C ^ 6 alkoxy, Cu haloalkoxy, C1-S alkyl cross acid group, CV6 alkylsilylene cross acid group, Cu burning sulfur, Cu alkoxy proposed group, CV6 alkyl group proposed gas-based, quasi-substituted aryl or heteroaryl ring two adjacent positions may form a 6 or 7 membered ring optionally substituted by a halogen carbocyclic or heterocyclic) or heteroaryl group (which may be optionally substituted by halogen, nitro, a cyano group, C1 ^ alkyl, Cp6 haloalkyl, C1 ^ alkoxy or Cu haloalkoxy, C ^ 4 alkoxy group intends, C ^ 6 alkyl Quasi-based gas, phenoxy group intends gas group (wherein the phenyl group optionally substituted by halogen, Cu alkyl, Cu burning group, Cy haloalkyl, CV4 haloalkoxy, cn, no2, aryl, heteroaryl, substituted amino or dialkylamino), amino, (V6 alkylamino or phenylamino (wherein the phenyl group optionally substituted by halogen, CV4 alkyl, Ci_4 alkoxy, Ci_4 haloalkyl, Ci_4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino) substituted).

[0043] 更优选的R1是Cu烷基、Cu卤代烷基、Cu烷氧基(U烷基、杂芳基(U烷基(其中杂芳基可任选被卤素、硝基、氰1基、C^6烷基、Cp6卤代烷基、C^6烷氧基、Cu卤代烧氧基、(V6烷基磺酰基、CV6烷基羰基取代，或杂芳环上两相邻位置可成环形成任选被卤素取代的5、6或7元碳环或杂环)、苯基(Cu)烷基(其中苯基可任选被卤素、C^4烷基、CV4烷氧基、CV4卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基、二烷基氨基、C1^6烷基磺酰基、CV6烷氧羰基取代，或苯环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、苯基(其可任选被被卤素、CV4烷基、Cu烷氧基、Cp4卤代烷基、Cu卤代烷氧基、CN、NO2、芳基、杂芳基、氣基、二烷基氣基、Cu烷基横酸基、C^6烧氧擬基取代，或苯环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)、杂芳基(其可任选被卤素、硝基、氰基、C1^烷基、C^6卤代烷基、C1^烷氧基、C^6卤代烷氧基、C^6烷基横酸基、C1^烷氧基擬基取代，或杂芳环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环XCh烷氧基、Cu卤代烷氧基、C2_6烯基、杂环基(其任选被卤素、氛基、C^6烷基、Cp6卤代烷基、C^6烷氧基或Cu卤代烷氧基取代)、C1^6烷硫基、Cu卤代烷硫基或NR13R14,其中R13和R14独立地是氢、C1^6烷基或CV6卤代烷基、C1^6烷氧基(C1J烷基、C2_6烷基羰基、苯基羰基(其中苯基可任选被卤素、CV4烷基、Cy烷氧基、Cy卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氣基或二烷基氣基取代)、苯基(Cu)烷基(其中苯基可任选被卤素、Cu烷基、CV4烧氧基、C1^4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基、二烷基氨基、C1^6烷基磺酰基、CV6烷氧基羰基取代，或苯环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)或杂芳基(Cu)烷基(其中杂芳基可任选被卤素、硝基、氰基、CV6烷基、C1^6卤代烷基、C1^烷氧基、C^6卤代烷氧基、C1^烷基横酸基、C^6烷基亚横酸基、C^6烧硫基、C1^烧氧基羰基、CV6烷基羰基氨基、芳基羰基取代，或杂芳环上两相邻位置可成环形成5、6或7元任选被卤素取代的碳环或杂环)。 [0043] More preferred R1 is an alkyl group Cu, Cu haloalkyl, Cu alkoxy (U alkyl, heteroaryl (U alkyl (wherein the heteroaryl may be optionally substituted by halogen, nitro, cyano group 1, C ^ 6 alkyl, Cp6 haloalkyl, C ^ 6 alkoxy, haloalkoxy burn the Cu group, (V6 alkylsulfonyl, CV6 substituted alkylcarbonyl group, or two adjacent positions heteroaromatic ring can form a ring formed optionally substituted by halogen, 6- or 7-membered carbocyclic or heterocyclic ring), phenyl (Cu) alkyl (wherein the phenyl group optionally substituted by halogen, C ^ 4 alkyl, CV4 alkoxy, CV4 haloalkyl , C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino, C1 ^ 6 alkylsulfonyl, CV6 substituted alkoxycarbonyl group, or two adjacent positions on the phenyl ring can be a 5, 6 or 7-membered ring formed optionally substituted by halogen carbocyclic or heterocyclic ring), a phenyl group (which may optionally be substituted with halogen, CV4 alkyl, Cu alkoxy, Cp4 haloalkyl, Cu haloalkoxy, CN, NO2, aryl, heteroaryl, gas, dialkyl gas-based, Cu cross acid alkyl group, C ^ 6 burn oxygen quasi-substituted, or two adjacent positions on the phenyl ring can be formed into a ring 5, 6 or 7-membered carbocyclic or heterocyclic ring optionally substituted with halogen), heteroaryl (which may be optionally substituted by halogen, nitro, cyano, C1 ^ alkyl, C ^ 6 haloalkyl, C1 ^ alkoxy , C ^ 6 haloalkoxy, C ^ 6 alkyl cross acid group, C1 ^ alkoxy substituted intended, or heteroaromatic ring two adjacent positions may form a 5,6 or 7-membered ring optionally substituted by halogen carbocyclic or heterocyclic XCh alkoxy, Cu haloalkoxy, C2_6 alkenyl group, a heterocyclic group (optionally substituted by halogen, atmosphere group, C ^ 6 alkyl, Cp6 haloalkyl, C ^ 6 alkoxy, or Cu haloalkoxy substituted), C1 ^ 6 alkylthio, Cu haloalkylthio or NR13R14, wherein R13 and R14 are independently hydrogen, C1 ^ 6 alkyl or CV6 haloalkyl, C1 ^ 6 alkoxy (C1J alkyl , C2_6 alkylcarbonyl, phenylcarbonyl (where the phenyl group is optionally substituted by halogen, CV4 alkyl, Cy-alkoxy, Cy haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, gas-gas or dialkylamino group-substituted), phenyl (Cu) alkyl (wherein the phenyl group optionally substituted by halogen, Cu alkyl, CV4 burn group, C1 ^ 4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino, dialkylamino, C1 ^ 6 alkylsulfonyl, CV6 substituted alkoxycarbonyl group, or two adjacent positions on the phenyl ring may be a 5, 6 or 7 ring forming Mototo substituted by halogen selected from carbocyclic or heterocyclic) or heteroaryl (Cu) alkyl (wherein the heteroaryl may be optionally substituted by halogen, nitro, cyano, CV6 alkyl, C1 ^ 6 haloalkyl, C1 ^ alkoxy group, C ^ 6 haloalkoxy, C1 ^ alkyl cross acid group, C ^ 6 alkylsulfinyl cross acid group, C ^ 6 burning sulfur, C1 ^ burn butoxycarbonyl, CV6 alkylcarbonylamino, aryl carbonyl substituted, or heteroaryl ring on two adjacent positions may form a 5,6 or 7-membered ring optionally substituted by a halogen carbocyclic or heterocyclic).

[0044] 甚至更优选的R1是Cu烷基、CV6卤代烷基、杂芳基(Cu)烷基(其中杂芳基可任选被卤素、氰基、CV6烷基、CV6卤代烷基取代，并且所述杂芳基是噻唑、吡啶、嘧啶、吡嗪或哒嗪)、杂芳基(其可任选被卤素、氰基、Ch6烷基、CV6卤代烷基取代，并且所述杂芳基是吡啶、嘧啶、2，I, 3-苯并噁二唑、批嗪或#嗪)、C1^6烷氧基、CV6烷氧基(U烷基、Cu烷基氨基、CV6烷氧基(CV6)烷基氣基或杂芳基(Cu)烷基氣基(其中所述杂芳基可任选被卤素、氛基、(V6烷基、Cu卤代烷基取代，并且所述杂芳基是噻唑、吡啶、嘧啶、吡嗪或哒嗪)。 [0044] Even more preferably, R1 is a Cu alkyl, CV6 haloalkyl, heteroaryl (Cu) alkyl (wherein the heteroaryl may be optionally substituted by halogen, cyano, CV6 alkyl, CV6 haloalkyl, and the said heteroaryl groups are thiazole, pyridine, pyrimidine, pyrazine or pyridazine), heteroaryl (which may be optionally substituted by halogen, cyano, Ch6 alkyl, CV6 haloalkyl substituted, and the heteroaryl is pyridine, pyrimidine, 2, I, 3- benzo oxadiazole, batch # piperazine or piperazine), C1 ^ 6 alkoxy, CV6 alkoxy (U alkyl, Cu alkylamino, CV6 alkoxy (CV6) alkyl group or heteroaryl group gas (Cu) gas alkyl group (wherein said heteroaryl may optionally be substituted by halogen, atmosphere group, (V6 alkyl, Cu haloalkyl substituted, and the heteroaryl is thiazole, pyridine , pyrimidine, pyrazine or pyridazine).

[0045] 最优选的是R1为吡啶基(任选被卤素、CV3烷基或Cu卤代烷基取代)，特别是卤代吡啶。 [0045] Most preferably R1 is pyridyl (optionally substituted by halogen, CV3 alkyl or haloalkyl substituted Cu), especially halogenated pyridine.

[0046] 优选的是R2为氧、羟基、C^6烷基或Cp6卤代烷基。 [0046] R2 is preferably oxygen, hydroxy, C ^ 6 alkyl or haloalkyl Cp6.

[0047] 最优选的是R2为氧、C^4烷基或CV4卤代烷基。 [0047] Most preferably R2 is oxygen, C ^ 4 alkyl or haloalkyl CV4.

[0048] 更优选的是R2为氢或Ch烷基。 [0048] More preferably, R2 is hydrogen or an alkyl group Ch.

[0049] 仍更优选的是R2独立地是氢或甲基。 [0049] Still more preferably R2 is independently hydrogen or methyl.

[0050] 最优选的R2是氢。 [0050] Most preferably R2 is hydrogen.

[0051] 优选的是R4各自独立地为卤素、氛基、Cu烷基、Ck卤代烷基、CV6氛基烷基、Cp6烧氧基(C1-J烷基、C3_7环烷基(Cp6)烷基、C5_6环烯基(Cp6)烷基、C3_6稀氧基(Cp6)烷基、C3_6炔氧基(Cu)烷基、芳氧基(Cu)烷基、Ch6羧基烷基、CV6烷基羰基(CV6)烷基、c2_6烯基羰基(CV6)烷基、C2_6炔基擬基(Cp6)烷基、CV6烧氧擬基(Cp6)烷基、C3_6稀氧基擬基(CV6)烧基、C3_6炔基擬基(CV6)烷基、芳氧基擬基(Cu)烷基、CV6烧硫基(CV6)烷基、Cu烷基亚横酰基(CV6)烷基、CV6烷基磺酰基(CV6)烷基、氨基羰基(CV6)烷基、CV6烷基氨基羰基(Cu)烷基、二(Cu)烷基氨基羰基(Cu)烷基、苯基(CV4)烷基(其中苯基任选被卤素、Cy烷基、(V4烷氧基、CV4卤代烷基、Cy卤`代烷氧基、cn、no2、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳基(U烷基(其中杂芳基任选被卤素、硝基、氰基、CV6烷基、CV6卤代烷基、Ch6烷氧基或CV6卤代烷氧基取代)、杂环基(CV4)烷基(其中杂环基任选被卤素、硝基、氛基、CV6烷基、C1-S卤代烷基、Cu烷氧基或Cp6卤代烷氧基取代)、C2_6烯基、氣基擬基(C2_6)烯基、Cu烷基氨基羰基(c2_6)烯基、二(U烷基氨基羰基(c2_6)烯基、苯基(c2_4)烯基(其中苯基任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氣基取代)、C2_6炔基、二甲娃烷基(C2_6)炔基、氣基擬基(C2_6)炔基、Cu烷基氣基擬基(C2_6)炔基、_.(C^6)烷基氣基擬基(C2_6)炔基、Cu烧氧擬基、C3_7环烷基、C3_7卤代环烷基、Ch氰1基环烷基、Cu烷基(C3_7)环烷基、Cu烷基(C3_7)卤代环烷基、苯基(任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳基(被卤素、硝基、氰基、Cu烷基、CV6卤代烷基、Ch6烷氧基或Cu卤代烷氧基取代)、杂环基(其中杂环基任选被卤素、硝基、氛基、C^6烷基、C1^卤代烷基、C^6烷氧基或CV6卤代烷氧基取代)，或2个相邻的R4与它们所相连的碳原子一起形成4、5、6或7元碳环或杂环，所述杂环或碳环可任选被卤素、Ci_8烷氧基、Ch6卤代烷氧基、苯氧基(任选被卤素、硝基、氰基、(V6烷基、CV6卤代烷基、Ch6烷氧基或Cu卤代烷氧基取代)、杂芳氧基(任选被卤素、硝基、氰基、Cu烷基、Cu卤代烷基、C1^6烷氧基或CV6卤代烷氧基取代)、C1^8烷硫基或r19r2°n取代，其中R19和R2°独立地是氢、CV8烷基、C3_7环烷基、C3_6烯基、C3_6炔基、C2_6卤代烷基、CV6烷氧羰基或R19和R2°与它们所相连的N原子一起形成五、六或七元杂环，所述杂环可进一步含有一个或两个选自O、N或S的杂原子并且其任选被一个或两个Cp6烷基取代；n是0、1、2 或3。 [0051] Preferably each R4 is independently halogen, group atmosphere, Cu alkyl, Ck haloalkyl, CV6 alkyl group atmosphere, Cp6 burn group (C1-J alkyl, C3_7 cycloalkyl (Cp6) alkyl , C5_6 cycloalkenyl (Cp6) alkyl, C3_6 alkoxy dilute (Cp6) alkyl, C3_6 alkynyloxy (Cu) alkyl, aryloxy (Cu) alkyl, Ch6 carboxyalkyl, CV6 alkylcarbonyl ( CV6) alkyl, c2_6 alkenylcarbonyl group (CV6) alkyl, C2_6 alkynyl group proposed (Cp6) alkyl, CV6 burning oxygen quasi-yl (Cp6) alkyl, C3_6 alkoxy thin quasi-yl (CV6) firing group, C3_6 Quasi alkynyl group (CV6) alkyl, aryloxy group proposed (Cu) alkyl, CV6 burning thio (CV6) alkyl, Cu alkylsulfinyl group horizontal (CV6) alkyl, CV6 alkylsulfonyl (CV6 ) alkyl, aminocarbonyl (CV6) alkyl, CV6 alkylaminocarbonyl (Cu) alkyl, di (Cu) alkylaminocarbonyl (Cu) alkyl, phenyl (CV4) alkyl (wherein phenyl is optionally It is halogen, Cy alkyl, (V4 alkoxy, CV4 haloalkyl, Cy 'halo alkoxy group, cn, no2, aryl, heteroaryl, amino or dialkylamino), heteroaryl (U alkyl (wherein the heteroaryl is optionally substituted by halogen, nitro, cyano, CV6 alkyl, CV6 haloalkyl, Ch6 CV6 alkoxy or haloalkoxy), heterocyclyl (CV4) alkyl (wherein the heterocycle group optionally substituted by halogen, nitro, atmosphere group, CV6 alkyl, C1-S haloalkyl, Cu Cp6 alkoxy or haloalkoxy), C2_6 alkenyl, gas-based quasi-yl (C2_6) alkenyl, Cu alkoxy aminocarbonyl group (c2_6) alkenyl, di (U alkylaminocarbonyl (c2_6) alkenyl, phenyl (c2_4) alkenyl (wherein the phenyl group optionally substituted by halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl , CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino group substituted with the gas), C2_6 alkynyl, baby dimethyl alkyl (C2_6) alkynyl, gas-based quasi-yl (C2_6) alkynyl group, Cu alkyl group quasi gas-yl (C2_6) alkynyl, _. (C ^ 6) alkyl group quasi gas-yl (C2_6) alkynyl, Cu quasi burning oxygen group, C3_7 cycloalkyl, C3_7 cycloalkyl halo group, Ch cyano cycloalkyl group 1, Cu alkyl (C3_7) cycloalkyl, Cu alkyl (C3_7) halocycloalkyl, phenyl (optionally substituted by halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl (substituted by halogen, nitro, cyano, Cu alkyl, CV6 haloalkyl, Ch6 Cu alkoxy or haloalkoxy group), a heterocyclic group (wherein the heterocyclic group is optionally substituted by halogen, nitro, atmosphere group, C ^ 6 alkyl, C1 ^ haloalkyl, C ^ 6 alkoxy or haloalkoxy CV6 alkoxy group), or two adjacent R4 together with the carbon atom to which they are attached form a 5, 6 or 7-membered carbocyclic or heterocyclic ring, the heterocyclic or carbocyclic ring optionally substituted with halogen, Ci_8 alkoxy group, Ch6 haloalkoxy, phenoxy (optionally substituted by halogen, nitro, cyano, (V6 alkyl, CV6 haloalkyl, Ch6 Cu alkoxy or haloalkoxy), heteroaryloxy (either is selected from halo, nitro, cyano, Cu alkyl, Cu haloalkyl, C1 ^ alkoxy or CV6 substituted 6 haloalkoxy group), C1 ^ 8 alkylthio or substituted r19r2 ° n, wherein R2 ° and R19 independently is hydrogen, CV8 alkyl, C3_7 cycloalkyl, C3_6 alkenyl, C3_6 alkynyl, C2_6 haloalkyl, CV6 alkoxycarbonyl or R19 and R2 ° N atom to which they are attached form a five, six or seven-membered heteroaryl ring, the heterocyclic ring may further contain one or two heteroatoms selected from O, N or S heteroatoms and optionally substituted by one or two substituents Cp6 alkyl; n is 2 or 3.

[0052] 甚至更优选R4各自独立地是卤素、氰基、C1^8烷基、C^8卤代烷基、C1^8氰基烷基、CV6烷氧基(CV6)烷基、C2_6炔基、二甲娃烷基(C2_6)炔基、Cu烷氧基擬基、C3_7环烷基、Cp3烷基(C3_7)环烷基、苯基(任选被卤素、Cu烷基、Cp4烷氧基、Cp4卤代烷基、Cu卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、杂环基(任选被卤素、硝基、氰基、Cu烷基、C1-S卤代烷基、C1^烷氧基或Cu卤代烷氧基取代)、C1^烷氧基、C^6卤代烷氧基、苯氧基(任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳氧基(任选被卤素、硝基、氰基、Cu烷基、CV3卤代烷基、Cu烷氧基或CV3卤代烷氧基取代)、二(Ci_8)烷氨基或2个相邻的R4与它们所相连的碳原子一起形成 [0052] Even more preferably R4 is independently halo, cyano, C1 ^ 8 alkyl, C ^ 8 haloalkyl, C1 ^ 8 cyanoalkyl, CV6 alkoxy (CV6) alkyl, C2_6 alkynyl, baby dimethyl alkyl (C2_6) alkynyl, Cu alkoxy group intends, C3_7 cycloalkyl, Cp3 alkyl (C3_7) cycloalkyl, phenyl (optionally substituted by halogen, Cu alkyl, Cp4 alkoxy, Cp4 haloalkyl, Cu haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heterocyclyl (optionally substituted by halogen, nitro, cyano, Cu alkyl, C1- S haloalkyl, C1 ^ alkoxy or haloalkoxy substituted Cu), C1 ^ alkoxy, C ^ 6 haloalkoxy, phenoxy (optionally substituted by halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl group, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryloxy (optionally substituted by halogen, nitro, cyano, Cu alkyl, CV3 haloalkyl , Cu CV3 alkoxy or haloalkoxy substituent), di (Ci_8) alkylamino or 2 adjacent R4 together with the carbon atom to which they are attached together form

4、5、6或7元碳环或杂环，所述杂环或碳环可任选被卤素取代；n是0、1、2或3。 5, 6 or 7-membered carbon ring or heterocyclic ring or carbon ring may be optionally substituted by halogen; n is 2 or 3.

[0053] 甚至更优选的R4各自独立地是卤素、氛基、CV8烷基、Cu卤代烷基、Ci_8氛基烷基、C1-S烷氧基(CV6)烷基、C2_6炔基、杂环基(任选被Cu烷基取代)、C1^烷氧基、Cu 1¾代烧氧基、苯氧基(任选被卤素、氰基、CV3烷基或CV3卤代烷基取代)、杂芳氧基(任选被卤素、氰基、CV3烷基或Cu卤代烷基取代)、二(Ci_8)烷基氨基或2个相邻的R4与它们所相连的碳原子一起形成4、5、6或7元碳环或杂环，所述杂环或碳环可任选被卤素取代；n是0、1、2或3。 [0053] Even more preferably, R4 is independently halo, atmosphere group, CV8 alkyl, Cu haloalkyl, Ci_8 atmosphere alkyl, C1-S alkoxy (CV6) alkyl, C2_6 alkynyl group, a heterocyclic group (optionally substituted Cu alkyl), C1 ^ alkoxy, Cu 1¾ behalf burn group, a phenoxy group (optionally substituted by halogen, cyano, CV3 CV3 alkyl or haloalkyl), heteroaryloxy ( optionally substituted by halogen, cyano, CV3 Cu alkyl or haloalkyl), di (Ci_8) alkylamino or 2 adjacent R4 together with the carbon atom to which they are attached form a 5, 6 or 7-membered carbon or a heterocyclic ring, the heterocyclic or carbocyclic ring which may optionally be substituted by halogen; n is 2 or 3.

[0054] 仍然优选的是R4独立地是氟、氯、溴、氰基、C1^4烷基、Cy卤代烷基、C1^4氰基烷基或Ch烷氧基(Ch)烷基；11是0、1、2或3，优选0、1或2。 [0054] Still preferably R4 is independently fluoro, chloro, bromo, cyano, C1 ^ 4 alkyl, Cy-haloalkyl, C1 ^ 4 cyanoalkyl or alkoxy Ch (Ch) alkyl; 11 2 or 3, preferably 0, 1 or 2.

[0055] 最优选的是R4各自独立地是氟、氯、溴、CV4烷基或Ch卤代烷基；n是1、2或3，优选I或2。 [0055] Most preferred is R4 is independently fluoro, chloro, bromo, CV4 Ch alkyl or haloalkyl; n is 1, 2 or 3, preferably I or 2.

[0056] 优选R8是C1,烷基、C1,卤代烷基、芳基(C1J烷基(其中芳基任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳基(Cu)烷基(其中杂芳`基任选被卤素、Cy烷基、Ch烷氧基、C1^4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、芳基羰基-(C1J烷基(其中所述芳基可任选被卤素、CV4烷基、Cy烷氧基、Cy卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代，和所述烷基可任选被芳基取代)、C2_8烯基、C2_8卤代烯基、芳基(C2_6)_烯基(其中芳基任选被卤素、Cy烷基、Cy烷氧基、Cy卤代烷基、Cy卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基、CV6烷氧基羰基取代，或两相邻取代基可成环形成5、6或7元碳环或杂环)、杂芳基(C2_6)_烯基(其中杂芳基任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基、C^6烷氧基羰基取代，或两相邻取代基可成环形成5、6或7元碳环或杂环)、C2_6炔基、苯基(C2_6)炔基(其中苯基任选被卤素、CV4烷基、Cy烷氧基、Cy卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氣基或二烷基氣基取代)、C3_7环烷基、Cu烧氧擬基、Cu烷基擬基、Cu卤代烷基擬基或芳基(C2_6)烯基擬基(其中芳基可任选被卤素、Cu烷基、Cu烷氧基、Cu卤代烷基、C1^4卤代烷氧基、CN、N02、芳基、杂芳基、氨基或二烷基氨基取代)或-C(R51) (R52)-[CR53=CR54]Z-R55，其中z是I或2，R51和R52各自独立地是H、卤素或CV2烷基，R53和R54各自独立地是H、卤素、C1^4烷基或CV4卤代烷基以及R55是任选取代的芳基或任选取代的杂芳基。 [0056] R8 is preferably C1, alkyl group, C1, haloalkyl, aryl (C1J alkyl (wherein aryl is optionally substituted with halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl, CV4 haloalkoxy, CN , NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl (Cu) alkyl (wherein the heteroaryl group is optionally substituted with halo ', Cy alkyl, Ch alkoxy, C1 ^ 4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), arylcarbonyl - (C1J alkyl (wherein the aryl group may be optionally substituted with halogen, CV4 alkyl group, Cy alkoxy, Cy haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino-substituted, and the alkyl group may be optionally substituted aryl) , C2_8 alkenyl, C2_8 haloalkenyl, aryl (C2_6) _ alkenyl (wherein the aryl group is optionally substituted with halogen, Cy alkyl, Cy-alkoxy, Cy haloalkyl, Cy haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino, CV6 substituted alkoxycarbonyl group, or two adjacent substituents may form a ring formed 5, 6 or 7-membered carbocyclic or heterocyclic ring), heteroaryl (C2_6) _ alkenyl (wherein the heteroaryl is optionally substituted with halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino, C ^ 6 alkoxycarbonyl substituted, or two adjacent substituents may form a ring formed 5, 6 or 7-membered carbocyclic or heterocyclic ring), C2_6 alkynyl, phenyl (C2_6) alkynyl (wherein the phenyl group optionally substituted by halogen , CV4 alkyl, Cy-alkoxy, Cy haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, gas-gas or dialkylamino group-substituted), C3_7 cycloalkyl, Cu burning Quasi-yl oxy, Cu alkyl group proposed, Cu haloalkyl group or an aryl group intended (C2_6) alkenyl group proposed (wherein the aryl group may be optionally substituted with halogen, Cu alkyl, Cu alkoxy, Cu haloalkyl, C1 ^ 4 haloalkoxy, CN, N02, aryl, heteroaryl, amino or dialkylamino) or -C (R51) (R52) - [CR53 = CR54] Z-R55, wherein z is I or 2, R51 and R52 are each independently H, halogen or CV2 alkyl, R53 and R54 are each independently H, halogen, C1 ^ 4 CV4 alkyl or haloalkyl and R55 is optionally substituted aryl or optionally substituted heteroaryl aryl.

[0057] 更优选的是R8是苯基(CV4)烷基(其中苯基任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、Cy卤代烷氧基、CN、N02、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳基(C1J烷基(其中杂芳基任选被卤素、CV4烷基、CV4烷氧基、Ch卤代烷基、Ch卤代烷氧基、CN、N02、#基、杂芳基、氨基或二烷基氨基取代)、苯基(C2_6)烯基(其中苯基任选被卤素、Cy烷基、CV4烷氧基、C1^4卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)、杂芳基(C2_6)烯基(其中杂芳基任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)或苯基(C2_6)炔基(其中苯基任选被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代)或-C (R51) (R52)-[CR53=CR54] Z-R55，其中z是I或2，R51和R52各自独立地是H、卤素或CV2烷基，R53和R54各自独立地是H、卤素、CV4烷基或Cy卤代烷基以及R55是任选取代的芳基或任选取代的杂芳基。 [0057] More preferably R8 is phenyl (CV4) alkyl (wherein the phenyl group optionally substituted by halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl, Cy haloalkoxy, CN, N02, aryl, heteroaryl, amino or dialkylamino), heteroaryl (C1J alkyl (wherein the heteroaryl is optionally substituted with halo, CV4 alkyl, CV4 alkoxy, Ch haloalkyl, Ch haloalkoxy, CN, N02, # group, heteroaryl, amino or dialkylamino), phenyl (C2_6) alkenyl (wherein the phenyl group optionally substituted by halogen, Cy alkyl, CV4 alkoxy, C1 ^ 4 haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino), heteroaryl (C2_6) alkenyl (wherein the heteroaryl is optionally substituted with halogen, CV4 alkyl, CV4 alkyl group, CV4 haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino) or phenyl (C2_6) alkynyl (wherein the phenyl group optionally substituted by halogen, alkyl CV4, CV4 alkoxy, CV4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino) or -C (R51) (R52) - [CR53 = CR54] Z-R55, where z is I or 2, R51 and R52 are each independently H, halogen or CV2 alkyl, R53 and R54 are each independently H, halogen, CV4 Cy alkyl or haloalkyl and R55 is any optionally substituted aryl or optionally substituted heteroaryl.

[0058]最优选的R8 是-C (R51) (R52) - [CR53=CR54] Z_R55，其中z 是I 或2，优选I，R51 和R52 各自独立地是H或CV2烷基，R53和R54各自独立地是H、卤素、CV4烷基或Cy卤代烷基以及R55是被卤素、CV4烷基、CV4烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氣基取代的苯基或被卤素、C^4烷基、C^4烷氧基、C^4卤代烷基、C^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代的杂芳基。 [0058] Most preferably R8 is -C (R51) (R52) - [CR53 = CR54] Z_R55, where z is I or 2, preferably I, R51 and R52 are each independently H or alkyl CV2, R53 and R54 are each independently H, halo, CV4 alkyl or haloalkyl and R55 Cy is halogen, CV4 alkyl, CV4 alkoxy, CV4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, gas or dialkyl amino group or a halogen-substituted phenyl, C ^ 4 alkyl, C ^ 4 alkoxy, C ^ 4 haloalkyl, C ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl group, an amino group or a dialkylamino-substituted heteroaryl.

[0059] 优选R51和R52是氢。 [0059] Preferably R51 and R52 are hydrogen.

[0060] 优选R53和R54是氢或卤素，尤其是氢。 [0060] R53 and R54 are preferably hydrogen or halogen, especially hydrogen.

[0061] 优选R55是被一至三个选自卤素、C1^4烷基、CV4烷氧基、Cy卤代烷基、C1^4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基的取代基取代的苯基。 [0061] R55 preferably is substituted by one to three substituents selected from halo, C1 ^ 4 alkyl, CV4 alkoxy, Cy haloalkyl, C1 ^ 4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or di alkylamino substituted phenyl substituents.

[0062] 优选Ra各自独立地是卤素、氰基、烷基、羟基或两个Ra基团与它们所相连的碳原子一起形成=0、=S、=NRb, =CRcRd,其中Rb、Re和Rd独立地是H或任选被取代的烷基，以及P是0、1或2。 [0062] Preferably Ra is independently halo, cyano, alkyl, hydroxy or two Ra groups together with the carbon atom to which they are attached form = 0, = S, = NRb, = CRcRd, wherein Rb, Re, and Rd are independently H or an optionally substituted alkyl, and P is 0, 1 or 2.

[0063] 最优选的是Ra各自独立地是氟、甲基、羟基或两个Ra基团与它们所相连的碳原子一起形成羰基，以及P是0、1或2。 [0063] Most preferred are Ra is independently fluoro, methyl, hydroxy or two Ra groups together with the carbon atom to which they are attached together form a carbonyl group, and P is 0, 1 or 2.

[0064] 最优选的是P为O。 [0064] Most preferred are P is O.

[0065] 优选的环 [0065] Preferred ring

[0066] [0066]

[0067] 是6-元芳环或5或6元杂芳环，其中环原子各自独立地为CH、S、N、NR4、0或CR4，条件是至少一个环原子不是CH或CR4且环中至多存在一个O或S原子。 [0067] is a 6-membered aromatic ring or a 5- or 6-membered heteroaromatic ring, wherein the ring atoms are each independently CH, S, N, NR4,0 or CR4, provided that at least one ring atom is not CH or CR4 and ring exist at most one O or S atom.

[0068] 更优选的环 [0068] More preferably, the ring

[0069] [0069]

[0070] 是苯、吡啶、嘧啶、吡嗪、哒嗪、三嗪、呋喃、噻吩、吡咯、咪唑、吡唑、噁唑、噻唑、异噁唑、异噻唑、[I, 2，3]三唑，[I, 2，3]噁二唑或[I, 2，3]噻二唑。 [0070] is benzene, pyridine, pyrimidine, pyrazine, pyridazine, triazine, furan, thiophene, pyrrole, imidazole, pyrazole, oxazole, thiazole, isoxazole, isothiazole, [I, 2,3] three oxazole, [I, 2,3] oxadiazole or [I, 2,3] thiadiazole.

[0071] 最优选的是环[0072] [0071] Most preferably, the ring [0072]

广一^^ A wide ^^

[0073] 为苯环或吡啶环。 [0073] is a benzene ring or a pyridine ring.

[0074] 一些式(I)的化合物是新的并因此形成本发明的另一个方面。 [0074] Some of the compounds of formula (I) are novel and thus form a further aspect of the present invention. 一种式I'的新化 One compound of formula I 'of Xinhua

合物 Compound

[0075] [0075]

[0076]其中 R1、R2、R4、Ra、t、y、n和p 如式I 中所定义，R8 是_C (R51) (R52)-[CR53=CR54] Z_R55，其中z是1或2，优选1，R51和R52各自独立地是H或CV2烷基，R53和R54各自独立地是H、卤素、Ch烷基或Cu卤代烷基以及R55是被卤素、C^4烷基、Cu烷氧基、Cu卤代烷基、C^4齒代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代的苯基或被卤素、C1^4烷基、Cy烷氧基、CV4卤代烷基、CV4卤代烷氧基、CN、NO2、芳基、杂芳基、氨基或二烷基氨基取代的杂芳基。 [0076] wherein R1, R2, R4, Ra, t, y, n and p are as defined in formula I, R8 is _C (R51) (R52) - [CR53 = CR54] Z_R55, wherein z is 1 or 2 , preferably 1, R51 and R52 are each independently H or alkyl CV2, R53 and R54 are each independently H, halo, Ch Cu alkyl or haloalkyl and R55 is halogen, C ^ 4 alkyl, Cu alkoxy group, Cu haloalkyl, C ^ 4 alkoxy group tooth, CN, NO2, aryl, heteroaryl, amino or dialkylamino or halo-substituted phenyl, C1 ^ 4 alkyl, Cy alkoxy , CV4 haloalkyl, CV4 haloalkoxy, CN, NO2, aryl, heteroaryl, amino or dialkylamino-substituted heteroaryl.

[0077] 通过下表1至XXV中的化合物来举例说明本发明化合物。 [0077] The following table 1 of compound XXV to illustrate the compounds of the present invention.

[0078] 表1中提供了897种式Ia的化合物 [0078] Table 1 provides 897 compounds of formula Ia

[0079] [0079]

[0080] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0080] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0081]表1 [0081] Table 1

[0082] [0082]

[0092] [0092]

[0100] [0100]

[0107] 表1I中提供了897种式Ib的化合物 [0107] Table 1I provides 897 compounds of formula Ib

[0108] [0108]

[0109] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [0109] where the definition of R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0110] 表1II中提供了897种式Ic的化合物 [0110] Table 1II provides 897 compounds of formula Ic

[0111] [0111]

[0112] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0112] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0113] 表1V中提供了897种式Id的化合物 [0113] Table 1V provides 897 compounds of formula Id

[0114] [0114]

[0115] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0115] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0116] 表V中提供了897种式Ie的化合物 [0116] Table V provides 897 compounds of formula Ie

[0117] [0117]

(Ie) (Ie)

[0118] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [01] which defines R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0119] 表VI中提供了897种式If的化合物 [0119] Table VI provides 897 compounds of formula If

[0120] [0120]

[0121] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0121] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0122] 表VII中提供了897种式Ig的化合物 [0122] Table VII provides 897 compounds of formula Ig

[0123] [0123]

[0124] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0124] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0125] 表VIII中提供了897种式Ih的化合物 [0125] Table VIII provides 897 compounds of formula Ih

[0126] [0126]

[0127] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [0127] where the definition of R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0128] 表1X中提供了897种式Ii的化合物 [0128] Table 1X provides a compound of Formula Ii 897 kinds of

[0129] [0129]

[0130] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0130] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0131] 表X提供了897种式Ij的化合物 [0131] Table X provides 897 compounds of formula Ij

[0132] [0132]

[0133] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0133] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0134] 表XI提供了897种式Ik的化合物 [0134] Table XI provides 897 compounds of formula Ik

[0135] [0135]

[0136] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [0136] where the definition of R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0137] 表XII提供了897种式Il的化合物 [0137] Table XII provides 897 compounds of formula Il

[0138] [0138]

[0139] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0139] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0140] 表XIII提供了897种式Im的化合物 [0140] Table XIII provides 897 compounds of formula Im

[0141] [0141]

[0142] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0142] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0143] 表XIV提供了897种式In的化合物 [0143] Table XIV provides 897 compounds of formula In

[0144] [0144]

[0145] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [0145] where the definition of R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0146] 表XV提供了897种式1的化合物 [0146] Table XV provides 897 kinds of compounds of Formula 1

[0147] [0147]

[0148] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0148] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0149] 表XVI提供了897种式Ip的化合物 [0149] Table XVI provides 897 compounds of formula Ip

[0150] [0150]

[0151] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0151] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0152] 表XVII提供了897种式Iq的化合物 [0152] Table XVII provides 897 compounds of formula Iq

[0153] [0153]

[0154] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0154] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0155] 表XVIII提供了897种式Ir的化合物 [0155] Table XVIII provides 897 compounds of formula Ir

[0156] [0156]

[0157] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [0157] where the definition of R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0158] 表XIX提供了897种式Is的化合物 [0158] Table XIX provides 897 compounds of formula Is

[0159] [0159]

[0160] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0160] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0161] 表XX提供了897种式It的化合物 [0161] Table XX provides 897 compounds of formula It

[0162] [0162]

[0163] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0163] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0164] 表XXI提供了897种式Iu的化合物 [0164] Table XXI provides 897 compounds of formula Iu

[0165] [0165]

[0166] 其中R8、R4a、R4\ R4c和R4d的定义如表1中所示。 [0166] where the definition of R8, R4a, R4 \ R4c and R4d are as shown in Table 1.

[0167] 表XXII中提供了897种式Iv的化合物 [0167] Table XXII provides 897 compounds of formula Iv

[0168] [0168]

[0169] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0169] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0170] 表XXIII中提供了897种式Iw的化合物 [0170] Table XXIII provides 897 compounds of formula Iw

[0171] [0171]

[0172] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0172] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0173] 表XXIV提供了110种式Ix的化合物 [0173] Table XXIV provides 110 compounds of formula Ix

[0174] [0174]

[0175] 其中R8、R4\ R4c和R4d的定义如表24中所示。 [0175] wherein R8, the definition of R4 \ R4c and R4d are as shown in Table 24.

[0176]表 24 [0176] Table 24

[0177] [0177]

[0181] 表XXV中提供了897种式Iy的化合物 [0181] Table XXV provides 897 compounds of formula Iy

[0182] [0182]

[0183] 其中R8、R4a、R4b、R4c和R4d的定义如表1中所示。 [0183] wherein R8, the definition of R4a, R4b, R4c and R4d are as shown in Table 1.

[0184] 可通过各种方法制备本发明化合物。 [0184] The compounds of this invention can be prepared by various methods. 例如他们可根据路线I的反应来制备。 For example, they can be prepared according to Scheme I reaction.

[0185]路线 I [0185] Scheme I

[0186] [0186]

[0187] 这样式I化合物可由合适的吸电子试剂和式2化合物反应制得。 [0187] Such a compound of formula I compounds may be suitable electron withdrawing reagents and type 2 reaction. 其中Y为羰基的式I化合物可通过式2化合物与式Rl-C(O)-Z的羧酸衍生物反应制得，其中Z是氯化物、羟基、烷氧基或酰氧基，所述反应是在0°C至150°C的温度下、在任选的有机溶剂例如二氯甲烷、氯仿或1，2-二氯乙烷中、在任选的叔胺碱例如三乙胺或二异丙基乙胺的存在下和任选的偶联剂例如二环己基碳二亚胺存在下进行的。 Compounds of formula I wherein Y is a carbonyl group may be prepared by a compound of formula 2 of the formula Rl-C (O) -Z prepared by reacting a carboxylic acid derivative, where Z is chloride, hydroxy, alkoxy or acyloxy, the The reaction is at a temperature between 0 ° C to 150 ° C, optionally in an organic solvent such as methylene chloride, chloroform or 1,2-dichloroethane, optionally in a tertiary amine base such as triethylamine or di in the presence of diisopropylethylamine and optionally a coupling agent for example dicyclohexyl carbodiimide in the presence of. 其中Y为羰基和Rl为式R' -NH-的胺取代基的式I化合物可通过式4化合物与式R' -N=C=O的异氰酸酯在类似的条件下反应制得。 Where 'a compound of formula I -NH- substituent amine compound of Formula 4 by the formula R' Y is a carbonyl group and Rl formula R -N = C = O isocyanate under conditions similar to the reaction. 其中Y为式S(O)ni的式I化合物可由式2化合物与式Rl-S(O)n1-Cl的化合物在类似条件下反应制得。 Compounds of formula I Y is the formula S (O) ni a compound of formula 2 of the formula by Rl-S (O) n1-Cl compounds under similar conditions reaction. 其中Y为硫羰基和Rl为式R' -NH-的胺取代基的式I化合物可通过式2化合物与式R' -N=C=S的异硫氰酸盐在类似的条件下反应制得。 'The compounds of formula I -NH- substituent amine compound of formula 2 by the formula R' wherein Y is sulfur carbonyl group and Rl formula R -N = C = S isothiocyanate under similar reaction conditions too.

[0188] 或者Y为硫代羰基且Rl为碳取代基的式I化合物可通过用合适的硫代硫酸盐试剂例如Lawesson' s试剂处理其中Y为羰基且Rl为碳取代基的式I化合物制得。 [0188] or Y is a thiocarbonyl group and a compound of formula I Rl is a carbon substituent may be prepared by using a suitable reagent such as thiosulfate Lawesson 's reagent wherein Y is a carbonyl group and substituent Rl carbon compound of the formula I too.

[0189] 在上述过程中的式Rl-C(O)-Z衍生物、式R' -N=C=O的异氰酸酯、式R' -N=C=S的异硫氰酸酯和式Rl-S (O) ,-Cl的亲电子试剂是已知化合物或可通过本领域技术人员已知的方法由已知化合物制得。 [0189] In the process of the formula Rl-C (O) -Z derivative of the formula R '-N = C = O of an isocyanate of formula R' -N = C = S isothiocyanate of the formula Rl -S (O), -Cl electrophiles are known compounds or may be made by methods known to those of skill was prepared from known compounds.

[0190] 式2化合物可根据本领域技术人员已知的方法通过还原式3化合物的硝基制得。 [0190] The compound of formula 2 can be prepared by reduction of nitro compounds of Formula 3 prepared according to the methods known to those skilled in the art.

[0191] 式3化合物可通过其中P为H的式6化合物与式R8-L的烷基化试剂，其中L是氯化物、溴化物、碘化物或磺酸酯(例如甲磺酸酯或甲苯磺酸酯)，或类似的离去基团在室温至IOO0C，一般为65°C的温度下，在有机溶剂例如二氯甲烷或1，2- 二氯乙烷中，在叔胺碱例如三乙胺或二异丙基乙胺的存在下和任选在卤化物盐例如碘化钠、碘化钾或碘化四丁铵的催化下反应制得。 Compound [0191] Formula 3 wherein P is H by Formula 6 and a compound of formula R8-L alkylating agents, wherein L is chloride, bromide, iodide or a sulfonate (e.g. mesylate or toluene sulfonate), or a similar leaving group at room temperature to IOO0C, generally at a temperature of 65 ° C, in an organic solvent such as dichloromethane or 1,2-dichloroethane, in a tertiary amine base such as tris in the presence of triethylamine or diisopropylethylamine and optionally under catalytic sodium iodide, potassium iodide or tetrabutylammonium halide salts such reaction. 或者，P为H的式6化合物可与式RzCHO的醛在室温至100°C的温度下、在有机溶剂例如四氢呋喃或乙醇或混合溶剂中、在还原剂例如硼烷-吡啶络合物、硼氢化钠、(三乙酰氧基)硼氢化钠、氰基硼氢化钠或这类类似物的存在下反应制得其中R8为CH2-Rz的式3化合物。 Alternatively, P is H the compound of formula 6 with an aldehyde of formula RzCHO be at a temperature of from room temperature to 100 ° C, in an organic solvent such as tetrahydrofuran or ethanol or a mixed solvent of a reducing agent such as borane - pyridine complex, boron sodium hydride, in the presence of (triacetoxy) of sodium borohydride, sodium cyanoborohydride or such like, reaction of a compound of Formula 3 CH2-Rz wherein R8 is prepared.

[0192] 或者，式I化合物可由式4化合物与酸例如三氟乙酸在室温下、在有机溶剂例如二氯甲烷、氯仿或1，2-二氯乙烷中反应，随后用无机碱例如碳酸钠、碳酸氢钠或类似化合物的水溶液中和反应(I)混合物；然后与上述烷基化剂或醛反应(2)制得。 [0192] Alternatively, compounds of formula I can be a compound of formula 4 with an acid such as trifluoroacetic acid at room temperature, in an organic solvent such as dichloromethane, chloroform or 1,2-dichloroethane in the reaction, an inorganic base such as sodium carbonate followed by , an aqueous solution of sodium bicarbonate or similar compound and reaction (I) mixtures thereof; and said alkylating agent or aldehyde (2) obtained.

[0193]如同上述的由式2化合物转化为式I化合物的方法,式4化合物可通过式5化合物与合适的亲电试剂反应制得。 [0193] As the compound represented by the above formula 2 is converted to a compound of formula I approach, a compound of Formula 4 with a suitable electrophilic reagent prepared by reacting a compound of formula 5.

[0194] 式5化合物可根据本领域已知的方法通过还原式6化合物的硝基制得，其中P是 [0194] Compounds of formula 5 can be prepared by reducing a compound of formula nitro-6 obtained according to methods known in the art, where P is

叔丁氧羰基。 T-butoxycarbonyl.

[0195] 式6化合物可通过式7化合物与哌嗪(P=H)或N-BOC-哌嗪(P=t_ 丁氧羰基)在(TC -180°C的温度下，在溶剂例如二氯甲烷、1，2-二氯乙烷、乙腈、二甲基甲酰胺或二甲亚砜中，在碱例如三乙胺、二异丙基乙胺或碳酸钾或没有碱的存在下反应制得。 [0195] The compound of formula 6 by a compound of formula 7 with piperazine (P = H) or N-BOC- piperazine (P = t_-butoxycarbonyl) at (TC -180 ° C at a temperature in a solvent such as dichloromethane methane, 1,2-dichloroethane, acetonitrile, dimethylformamide or dimethyl sulfoxide, in the presence of a base such as triethylamine, diisopropylethylamine or potassium carbonate or without the presence of a base prepared by reacting .

[0196] 式5、式6和式7是已知化合物或可通过已知方法由已知化合物制得。 [0196] Formula 5, Formula 6 and Formula 7 are known compounds or may be obtained by known methods from known compounds prepared.

[0197] 一些式2、式3和式4的化合物是新的并因此形成本发明的另一个方面。 [0197] Some of Formula 2, the compound of Formula 3 and Formula 4 are novel and therefore form a further aspect of the present invention.

[0198] 本领域技术人员应该很容易认识到能够将其中R2为H的式I化合物或路线I中的中间体转化成另一种式I的化合物。 [0198] Those skilled in the art should readily be able to recognize that wherein R2 is H or a compound of formula I in Scheme I Another intermediate compound of formula I is converted. 路线2、3和4中给出了这种转化的例子，其中R基团具有上述式I化合物所述定义。 Route 2, 3 and 4 shows an example of this transformation, wherein said R group is a compound having the formula I defined.

[0199] [0199]

消灭和防治的害虫包括那些与农业(所述术语包括食用和纤维产品作物种植)、园艺和畜牧业、伴生动物、林业和贮藏植物源产品(例如水果、粮食和木料)相关的害虫；那些与损害人造组织和传播人和动物疾病相关的害虫；以及公害害虫(例如苍蝇)。 Eradication and control of pests include those with agriculture (the term includes edible crops and fiber products), horticulture and animal husbandry, companion animals, forestry and the storage of products of plant origin (such as fruit, grain and timber) related pests; those with artificial tissue damage and the spread of pests and animal diseases; and nuisance pests (such as flies).

[0201] 通过式(I)化合物防治害虫种类的例子包括:桃姆(Myzus persicae)、棉虫牙(Aphis gossypii)、甜菜姆(Aphis fabae)、盲蝽属(Lygus spp.)、红蝽属(Dysdercusspp.)、褐飞風(Nilaparvata lugens)、黑尾叶蜂(Nephotettixc incticeps)、绿鋳属(Nezara spp.)、褐鋳属(Euschistus spp.)、蛛缘鋳属(Leptocorisa spp.)、苜猜蓟马(Frankliniella occidentalis)、蓟马属(Thrips spp.)、马铃薯叶甲(Leptinotarsadecemlineata)、野棉铃象甲(Anthonomus grandis)、圆阶属(Aonidiella spp.)、粉風(Trialeurodes spp.)、棉粉風(Bemisia tabaci)、欧洲玉米螟(Ostrinia nubilalis)、贪棉夜蛾(Spodoptera littoralis)、烟草夜蛾(Heliothis virescens)、棉铃虫(Helicoverpa armigera)、谷实夜蛾(Helicoverpa zea)、棉卷叶野螟(Syleptaderogata)、大菜粉蝶(Pieris brassicae)、菜蛾(Plutella xylostella)、地老虎属(Agrotis spp.)、二化螟(Chilo suppressalis)、飞虫皇(Locusta migratoria)、Chortiocetes terminifera、叶甲属(Diabrotica spp.)、苹果红蜘蛛(Panonychusulmi)、柑桔红蜘蛛(Panonychus citri)、棉红蜘蛛(Tetranychus urticae)、朱砂叶螨(Tetranychus cinnabarinus)、柑桔镑瘦螨(Phyllocoptruta oleivora)、侧多食跑线螨(Polyphagota rsonemus latus)、短须螨属(Brevipalpus spp.)、微小牛蜱(Boophilusmicroplus)、变异革蜱(Dermacentor variabi I is)、猫丰节头蚤(Ctenocephalides felis)、潜妮属(Liriomyza spp.)、家妮(Musca domestica)、埃及伊蚊(Aedes aegypti)、按蚊属(Anopheles spp.)、库蚊属(Culex spp.)、绿妮属(Lucillia spp.)、德国小爐(Blattellagermanica)、美洲大爐(Periplaneta americana)、东方蜚爐(Blatta oriental is)、下列各科白蚁:澳白蚁科(例如Mastotermes spp.)、木白蚁科(例如Neotermes spp.)、犀白蚁科(例如家白蚁(Coptotermes formosanus);黄枝散白蚁属(Reticulitermes flavipes)、黄胸散白蚁属(R.speratu)、南方散白蚁(R.virginicus)、美国散白蚁(R.hesperus)和R.santonensis 以及白蚁科(例如黄球白蚁(Globitermes sulphureus))、Solenopsisgeminata (火蚁)、厨蚁(Monomorium pharaonis)、卩齿風属(Damalinia spp.)和长颚風属(Linognathus spp.)、根结线虫属(Meloidogyne spp.)、球异皮线虫属(Globoderaspp.)和异皮线虫属(Heterodera spp.)、草地垫刃线虫属(Pratylenchus spp.)、香蕉洞线虫(Rhodopholus spp.)、垫刀线虫属(Tylenchulus spp.)、擒转血矛线虫(Haemonchuscontortus)、秀_ 隐杆线虫(Caenorhabditis elegans)、毛圆线虫属(Trichostrongylusspp.)和庭园灰赔輸(Deroceras reticulatum)。 [0201] The formula (I) Examples of compounds for the control of pest species include: (. Lygus spp) Peach Farm (Myzus persicae), cotton cavities (Aphis gossypii), Tim beet (Aphis fabae), Lygus spp., Red bugs belong ( Dysdercusspp.), brown fly wind (Nilaparvata lugens), black-tailed sawfly (Nephotettixc incticeps), green Zhu genus (Nezara spp.), brown Zhu genus (Euschistus spp.), edge Zhu spider genus (Leptocorisa spp.), clover Guess thrips (Frankliniella occidentalis), Thrips (Thrips spp.), Colorado potato beetle (Leptinotarsadecemlineata), wild boll weevil (Anthonomus grandis), round-order genus (Aonidiella spp.), pink wind (Trialeurodes spp.), cotton pink wind (Bemisia tabaci), the European corn borer (Ostrinia nubilalis), greed cotton armyworm (Spodoptera littoralis), tobacco budworm (Heliothis virescens), bollworm (Helicoverpa armigera), zea (Helicoverpa zea), Cotton leaf curl borer (Syleptaderogata), large cabbage butterfly (Pieris brassicae), diamondback moth (Plutella xylostella), cutworm genus (Agrotis spp.), rice stem borer (Chilo suppressalis), flies Wong (Locusta migratoria), Chortiocetes terminifera, Diabrotica spp. (Diabrotica spp.), apple red spider (Panonychusulmi), citrus red mite (Panonychus citri), spotted spider mite (Tetranychus urticae), carmine spider mite (Tetranychus cinnabarinus), citrus pound lean mites (Phyllocoptruta oleivora) side running to eat mites (Polyphagota rsonemus latus), Brevipalpus genus (Brevipalpus spp.), Boophilus (Boophilusmicroplus), variation Dermacentor (Dermacentor variabi I is), cat flea abundance section header (Ctenocephalides felis), latent ni genus (Liriomyza spp.), home-ni (Musca domestica), the Aedes aegypti mosquito (Aedes aegypti), Anopheles (Anopheles spp.), Culex (Culex spp.), green-ni belongs (Lucillia spp.) German small furnace (Blattellagermanica), Americana furnace (Periplaneta americana), Eastern enjoys furnace (Blatta oriental is), the following subjects termite: (example Mastotermes spp) (. For example Neotermes spp) Australia Termitidae, wood termites Branch, rhinoceros Termitidae (such as termite (Coptotermes formosanus); Huang Chih-termite genus (Reticulitermes flavipes), speratus genus (R.speratu), South termite (R.virginicus), United States termite (R.hesperus) and R.santonensis and termite families (such as the yellow ball termites (Globitermes sulphureus)), Solenopsisgeminata (fire ants), kitchen ants (Monomorium pharaonis), Jie teeth wind genera (Damalinia spp.) and the long jaw wind genera (Linognathus spp.) nematode genera (Meloidogyne spp.), leather ball different nematode genera (Globoderaspp.) and different skin nematode genera (Heterodera spp.), the grass mat edge nematode genera (Pratylenchus spp.), banana hole nematode (Rhodopholus spp.) , mat knife nematode genera (Tylenchulus spp.), capture turn Haemonchus (Haemonchuscontortus), show _ C. elegans (Caenorhabditis elegans), hair nematodes genus (Trichostrongylusspp.) and garden gray lose lose (Deroceras reticulatum).

[0202] 本发明因此还提供一种杀灭和防治昆虫、螨虫、线虫或软体动物的方法，其包括对害虫、害虫的栖息地或易受害虫侵害的植物施用杀昆虫、杀螨、杀线虫或杀软体动物有效量的式(I)化合物或含式(I)化合物的组合物，优选式(I)化合物用于抗昆虫、螨虫或线虫。 [0202] The present invention therefore also provides a kill and insects, mites, nematodes or molluscs control, which includes insects, pests or habitat of plants susceptible to pests applying insecticides, nematicidally composition comprising a compound or molluscicidally effective amount of a compound of formula (I) having the formula or (I), preferred compounds of formula (I) for use against insects, mites or nematodes.

[0203] 这里所使用的术语“植物”包括秧苗、灌木和树木。 [0203] As used herein, "plant" includes seedlings, bushes and trees.

[0204] 为了对害虫、害虫栖息地或易于受害虫侵害的植物施用作为杀虫剂、杀螨剂、杀线虫剂或杀软体动物剂的式(I)化合物，通常将式(I)化合物配制成组合物形式，该组合物除含式(I)化合物之外，还含有合适的惰性稀释剂或载体和任选的表面活性剂(SFA)。 [0204] In order to pests, pests or habitat of pests of plants susceptible administered as insecticides, acaricides, nematicides compound or molluscicide of formula (I), the compound is usually formulated formula (I) into the form of a composition, the composition containing compound in addition to formula (I), but also contain a suitable inert diluent or carrier and optionally, a surface active agent (SFA). SFA是能通过降低界面张力改善界面(例如液体/固体、液体/空气或液体/液体界面)性质并因此导致其它性质(例如分散性、乳化性和湿润性)发生改变的化学物质。 SFA is improved by reducing the interfacial tension of the interface (e.g., liquid / solid, liquid / air or liquid / liquid interface) and thus to the nature of other properties (for example dispersion, emulsification and wetting) chemical change. 优选所有组合物(包括固体和液体制剂)都包含0.0001-95%重量、更优选1-85%重量，例如5-60%重量的式(I)化合物。 Preferably all compositions (both solid and liquid formulations including) contains 0.0001% by weight, more preferably 1-85% by weight, e.g., 5-60% by weight of the compound of formula (I). 本发明组合物通常以每公顷施用0.lg-lOkg，优选每公顷lg_6kg，更优选每公顷Ig-1kg的式(I)化合物的方式用于防治害虫。 The compositions of the invention are usually administered per hectare 0.lg-lOkg, preferably per hectare lg_6kg, more preferably the compounds of Ig-1kg per hectare of formula (I) for controlling pests.

[0205] 当用于拌种时，式(I)化合物的用量为每千克种子0.0OOlg-1Og (例如0.0Olg或0.05g)，优选0.005g-10g,更优选0.005g-4g。 [0205] When used in a seed dressing, the amount of the compound of formula (I) per kilogram of seed 0.0OOlg-1Og (e.g. 0.0Olg or 0.05g), preferably 0.005g-10g, more preferably 0.005g-4g.

[0206] 另一方面本发明提供一种杀昆虫、杀螨、杀线虫或杀软体动物的组合物，其含有有效量的杀昆虫、杀螨、杀线虫或杀软体动物的式(I)化合物和合适的载体或稀释剂。 [0206] Another aspect of the invention provides an insecticidal, acaricidal, nematicidal or molluscicidal composition comprising an effective amount of a compound of insecticidal, acaricidal, nematicidal or molluscs formula (I) and a suitable carrier or diluent. 所述组合物优选是杀昆虫、杀螨、杀线虫或杀软体动物的组合物。 The composition is preferably insecticidal, acaricidal, nematicidal or composition of mollusks.

[0207] 再一方面，本发明提供了一种在栖息地杀灭和防治害虫的方法，该方法包括用杀昆虫、杀螨、杀线虫或杀软体动物有效量的包含式(I)化合物的组合物处理害虫或害虫栖息地。 [0207] In another aspect, the present invention provides a habitat for killing and pest control method, the method comprising insecticidal, acaricidal, nematicidal or molluscs contain an effective amount of Formula (I) compounds composition treatment of pests or pest habitats. 式(I)化合物优选用于抗昆虫、螨虫或线虫。 The compounds of formula (I) preferably used against insects, mites or nematodes.

[0208] 本发明组合物可以选自多种制剂类型，包括可喷粉粉剂(DP)、可溶性粉剂(SP)、水溶性颗粒剂(SG)、水分散颗粒剂(WG)、可湿性粉剂(WP)、颗粒剂(GR)(缓慢或快速释放)、可溶性浓缩物(SL)、油混溶性液剂(0L)、超低量液剂(UL)、浓缩乳剂(EC)、可分散浓缩物(DC)、乳剂(包括水包油型(EW)和油包水型(E0))、微乳剂(ME)、悬浮剂(SC)、气雾剂、成雾剂/烟剂、胶囊悬浮剂(CS)和种子处理剂型。 [0208] The compositions of the invention may be selected from a number of formulation types, including dusting powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powder ( WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (0L), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (including oil-in-water (EW) and water in oil type (E0)), micro-emulsions (ME), suspensions (SC), aerosols, fogging agents / smoke, capsule suspensions (CS) and seed treatment formulations. 在任情况下剂型类型的选择均取决于所预想的具体目的和本发明式(I)化合物的物理、化学以及生物学性质。 In either case formulation type selection are dependent on the physical, chemical and biological properties of the compounds envisioned and the specific purpose of the invention of the formula (I).

[0209] 可如下制备可喷粉粉剂(DP):将式(I)化合物与一种或多种固体稀释剂(例如天然粘土，高岭土，叶蜡石，膨润土，矾土，蒙脱石，硅藻石，碳酸钙，硅藻土，磷酸钙，磷酸钙和磷酸镁，硫磺，石灰，面粉，滑石及其它有机的和无机的固体载体)混和，并将此混合物机械研磨成细粉末。 [0209] Dusting powders may be prepared as follows (DP): the formula (I) compound with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, silicon alginate, calcium carbonate, diatomaceous earth, calcium phosphate, calcium phosphate and magnesium phosphate, sulfur, lime, flours, talc and other organic and inorganic solid carriers) is mixed, and the mixture was mechanically ground to a fine powder.

`[0210] 可如下制备可溶性粉剂(SP):将式(I)化合物与一种或多种水溶性无机盐(如碳酸氢钠、碳酸钠或硫酸镁)或一种或多种水溶性有机固体(例如多醣)、以及一种或多种任选的用于改善水分散性/溶解性的润湿剂、一种或多种分散剂或所述物质的混合物相混和。 `[0210] Soluble powders may be prepared as follows (SP): the formula (I) compound with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (e.g. polysaccharides), and one or more optional wetting agent for improving the water dispersibility / solubility, and mixtures of one or more dispersing agents or mixed the substance. 然后将此混合物研磨成细粉末。 The mixture is then ground to a fine powder. 类似的组合物也可以颗粒化以形成水溶性颗粒剂(SG)。 Similar compositions may also be granulated to form water soluble granules (SG).

[0211] 可湿性粉剂(WP)可通过将式(I)化合物与一种或多种固体稀释剂料或载体、一种或多种润湿剂、和优选一种或多种分散剂以及任选的一种或多种用于促进液体分散的悬浮剂相混和来制备。 [0211] Wettable powders (WP) may be prepared by any one of Formula (I) compound with one or more solid diluents or carrier material, one or more wetting agents and, preferably, one or more dispersants and selected from one or more suspending agents for facilitating dispersion liquid is mixed and prepared. 然后将此混合物研磨成细粉末。 The mixture is then ground to a fine powder. 类似地也可以颗粒化组合物以形成水分散颗粒剂(WG)。 Similarly, the composition may also be granulated to form water dispersible granules (WG).

[0212] 颗粒剂(GR)可通过如下方法形成:颗粒化式(I)化合物和一种或多种粉状固体稀释剂或载体的混合物，或利用预先形成的空白颗粒剂在多孔颗粒物质(如浮石、山软木土、漂白土、硅藻石、硅藻土或玉米穗轴粉)中吸收式(I)化合物(或其在适宜试剂中的溶液)，或将式(I)化合物(或其在适宜试剂中的溶液)吸附到硬核物质(如砂子，硅酸盐，矿物质碳酸盐，硫酸盐或者磷酸酯)上来制备，如有必要，再加以干燥。 [0212] Granules (GR) may be formed by the following method: a mixture of particles of the formula (I) compound and one or more powdered solid diluents or carriers, or the use of pre-formed blank granules in porous particulate matter ( such as pumice, mountain cork earth, fuller's earth, diatomaceous stone, diatomaceous earth or corn cob flour) absorption of formula (I) compound (or its solution in a suitable agent), or the formula (I) compound (or its solution in a suitable agent) on to a hard core material (such as sand, silicates, minerals, carbonates, sulfates or phosphates) onto prepared, if necessary, followed by drying. 通常用于助吸收或吸附的试剂包括溶剂(例如脂肪族的和芳香族的石油类溶剂、醇、醚、酮和酯)和粘着剂(例如聚醋酸乙烯酯、聚乙烯醇、糊精、糖和植物油)。 Agents are generally used in assisted absorption or adsorption include solvents (e.g., petroleum-based solvents and aromatic aliphatic alcohols, ethers, ketones and esters) and sticking agents (e.g., polyvinyl acetate, polyvinyl alcohol, dextrin, sugar and vegetable oils). 颗粒剂中也可包括一种或多种其它的添加剂(例如乳化剂、润湿剂或分散剂)。 Granules may also include one or more other additives (e.g. emulsifiers, wetting or dispersing agent). [0213] 可分散浓缩物(DC)可通过在水中或有机溶剂如酮、醇类或乙二醇醚中溶解式(I)化合物来制备。 [0213] Dispersible concentrates (DC) can be in water or an organic solvent such as a ketone, alcohol or glycol ether is dissolved in Formula (I) compound is prepared. 这些溶液中可含有表面活性剂(例如用于改善水稀释性或防止在喷洒器中结晶)。 These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallization in a nebulizer).

[0214] 浓缩乳剂(EC)或水包油乳化剂(EW)可通过在有机溶剂(任选的包含一种或多种润湿剂、一种或多种乳化剂或所述物质的混合物)中溶解式(I)化合物来制备。 [0214] Emulsifiable concentrates (EC) or oil-in-water emulsifier (EW) can be prepared by an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of the substance) The compound was dissolved Formula (I) is prepared. EC中所用的合适有机溶剂包括芳香烃(如烷基苯或烷基萘，其实例有S0LVESS0100、S0LVESS0150和S0LVESS0200 ；S0LVESS0是注册商标)、酮(如环己酮或甲基环己酮)、醇类(如苯甲醇、糠醇或丁醇)、N-烷基吡咯烷酮(如N-甲基吡咯烷酮或N-辛基吡咯烷酮)、脂肪酸的二甲基酰胺(如C8-C10脂肪酸二甲基酰胺)和氯代烃。 EC in a suitable organic solvent used include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified S0LVESS0100, S0LVESS0150 and S0LVESS0200; S0LVESS0 is a registered trademark), ketones (such as cyclohexanone or methylcyclohexanone), alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N- alkylpyrrolidones (such as N- methylpyrrolidone or N- octylpyrrolidone), dimethyl amides of fatty acids (such as C8-C10 fatty acid dimethylamide) and chlorinated hydrocarbons. EC产物加水可自然乳化，生成具有足够稳定性的乳化液，从而可通过适当的设备进行喷洒施肥。 EC product water naturally emulsified to produce an emulsion with sufficient stability, so that fertilization can be sprayed by suitable means. EW的制备包括获得液体形式(如果在室温下不是液体，其可在适当的温度下融化，一般温度低于70°C)或溶液形式(通过在适当的溶剂中溶解所得)的式(I)化合物，然后在高剪切刀下将生成的液体或溶液在含有一种或多种SFA的水中乳化，从而制备得到乳化液。 Preparation EW involves obtaining a liquid form (if not a liquid at room temperature, it may be melted at a suitable temperature, generally a temperature below 70 ° C) or in solution (obtained by dissolving in a suitable solvent) of the formula (I) compound, then the high shear generated by the sword in a liquid or a solution containing one or more emulsifying SFA water so as to prepare an emulsion. EW中使用的合适溶剂包括植物油、氯代烃(如氯苯)、芳香族溶剂(如烷基苯或烷基萘)和其它适当的在水中具有低溶解度的有机溶剂。 Suitable solvents for use in the EW include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents having a low solubility in water.

[0215] 微乳剂(ME)可通过将水与一种或多种溶剂和一种或多种SFA的混合物混合来制备，从而自发地生成热力学稳定的均质液体制剂。 [0215] Microemulsions (ME) may be prepared by a mixture of water and one or more solvents and one or more of the SFA prepared by mixing, so as to generate spontaneously a thermodynamically stable homogenous liquid formulation. 式(I)化合物开始存在于水中或溶剂/SFA的混合物中。 Mixture of formula (I) compounds initially present in water or solvent / SFA's. 在ME中使用的合适溶剂包括上面所描述的在EC或EW中使用的那些溶剂。 Suitable solvents for use in ME include those solvent used in the EC or EW described above. ME可以是水包油或者油包水体系(这种体系可通过电导率测量来测定)，并且适于与同一制剂中的水溶性和油溶性杀虫剂相混和。 ME may be water-in-oil or oil-in-water system (such a system may be determined by conductivity measurements), and adapted to the same formulation with water-soluble and oil-soluble pesticides and mixed. ME适于在水中稀释，稀释后仍然可保持为微乳剂或形成常规的水包油乳剂。 ME is suitable for dilution into water, diluted microemulsion can still be maintained at or forming a conventional oil in water emulsion.

[0216] 悬浮剂(SC)可包括式(I)化合物不溶性细碎固体颗粒的水性或非水性悬浮剂。 Compound [0216] suspensions (SC) may comprise the formula (I) finely divided insoluble solid particles of an aqueous or non-aqueous suspension. SC的制备包括用球磨或珠磨研磨在合适介质中的式(I)化合物来制备，任选具有一种或多种分散剂，从而制得所述化合物的颗粒悬浮剂。 The SC was prepared by ball or bead milling comprises milling in a suitable medium, of formula (I) of the compound prepared, optionally with one or more dispersing agents, to thereby obtain the compound particle suspension. 此类组合物中可以包含一种或多种润湿剂和用于降低颗粒下沉速率的悬浮剂。 Such compositions may comprise one or more wetting agents and means for reducing the rate of sinking particles suspending agents. 或者，可将式(I)进行干燥研磨并将其添加到含上述物质的水中，从而制备得到所需的最终产物。 Alternatively, the formula (I) was dried milled and added to water containing these substances, to prepare the desired final product.

[0217] 气雾剂包含式(I)化合物`和合适挥发剂(例如正丁烷)。 [0217] aerosol comprising the formula (I) and a suitable propellant `compound (e.g. n-butane). 还可将式(I)化合物溶解或分散在合适介质(例如水或水乳液，如正丙醇)中从而形成供在非压、手动喷洒泵中使用的组合物。 The compound may also be dissolved or dispersed in a suitable medium (e.g., water or an aqueous emulsion, such as n-propanol) of formula (I), for thereby forming a non-pressure, manual spray pump for use in the compositions.

[0218] 式(I)化合物可在干燥状态下与烟火混合物相混和以形成适于在封闭场所产生含所述化合物烟雾的组合物。 [0218] Formula (I) compounds can be mixed with a pyrotechnic mixture in the dry state and to form adapted to generate smoke containing the compound compositions in enclosed spaces.

[0219] 胶囊悬浮剂(CS)可以类似于制备EW剂型的方式制备，但还包括附加的聚合步骤，从而获得油珠的水分散体，其中每滴油珠是被聚合壳密闭，并且包含式(I)的化合物和任选的载体或稀释剂。 [0219] Capsule suspensions (CS) may be prepared in an analogous way to the preparation of EW formulations but also includes additional polymerization step to obtain an aqueous dispersion of oil droplets, wherein each drip beads are polymerized shell sealed, and comprises the formula (I) compounds and, optionally, a carrier or diluent. 所述聚合壳可通过界面缩聚反应或者凝聚过程来制备。 The polymeric shell interface or by condensation reaction may be prepared by agglomeration process. 所述组合物可提供式(I)化合物的控制释放，它们可用于种子处理。 The composition may provide the formula (I) controlled release of the compound, which may be used for seed treatment. 式(I)化合物也可以用生物降解聚合物基体来配制，从而形成化合物的缓慢、控制释放。 Formula (I) compounds can also be used a biodegradable polymeric matrix to be formulated so as to form a compound of slow, controlled release.

[0220] 组合物可含有用于改善所述组合物的一种或多种添加剂(例如通过改善湿润性、表面保持性或分配性；处理表面的耐雨性；或式(I)化合物的吸收性或流动性)。 [0220] The composition can be used to improve the composition comprising one or more additives (e.g., by improving wetting, retention or distribution of the surface; resistance to rain on treated surfaces; or a compound of formula (I) of the absorbent or liquidity). 这类添加剂包括表面活性剂，油基雾化添加剂，例如某些矿物油或天然植物油(如黄豆和菜籽油)，以及它们和其它生物增强助剂(能增强或改善式(I)化合物的作用效果)的混合物。 Such additives include surface active agents, oil-based spray additives, for example certain mineral oils or natural plant oils (such as soybean and rapeseed), as well as their biological and other enhancement additives (to enhance or improve a compound of formula (I), effect) was. [0221] 式(I)化合物还可用于配制成拌种剂，例如配制成粉剂组合物，包括用于干种子处理(DS)的粉剂、水溶性粉剂(SS)或用于浆液处理(WS)的可湿性粉剂，或配制成液体组合物，包括流动的浓缩物(FS)、溶液(LS)或胶囊悬浮剂(CS)。 Compound [0221] of formula (I) may also be formulated for seed dressing agents, e.g., formulated as a powder composition, including for dry seed treatment (DS) powder, a water soluble powder (SS) or for slurry treatment (WS) wettable powder, or formulated as a liquid composition, including flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). DS、SS、WS、FSjP LS组合物的制备分别与上面所描述的DP、SP、WP、SC和DC组合物的那些制备很相似。 DS, SS WS preparation,, FSjP LS compositions are described above with the DP, who prepared SP, WP, SC and DC compositions are very similar. 用于处理种子的组合物可包含有助于组合物对种子粘附的物质(例如矿物油或成膜防护物)。 The composition for treating seed may include seed composition helps adhesion substances (e.g., mineral oil or a film-forming shield).

[0222] 润湿剂、分散剂和乳化剂可以是阳离子、阴离子、两性或非离子型的表面SFA。 [0222] Wetting agents, dispersing agents and emulsifying agents may be surface SFA cationic, anionic, amphoteric or non-ionic type.

[0223] 合适的阳离子型SFA包括季铵化合物(例如溴化十六烷基三甲铵)、咪唑啉以及胺盐。 [0223] Suitable cationic SFA include quaternary ammonium compounds (such as cetyl trimethyl ammonium bromide), imidazolines and amine salts.

[0224] 合适的阴离子SFA包括脂肪酸碱金属盐，硫酸脂肪族单酯的盐(例如十二烷基硫酸钠)，磺化芳族化合物的盐(例如十二烷基苯磺酸钠、十二烷基苯磺酸钙、丁基萘磺酸盐以及二异丙基-和三异丙基-萘磺酸钠的混合物)，醚硫酸盐，醇醚硫酸盐(例如月桂醚-3-硫酸钠)，醚羰酸盐(例如月桂醚-3-羧酸钠)，磷酸酯(一种或多种脂肪醇和磷酸的反应产物(主要是单酯)或与磷酸酐的反应产物(主要是双酯类)，例如月桂醇和四磷酸的反应产物；另外这些也可以被乙氧基化)，磺基琥珀酰胺酸盐，石蜡或链烯烃磺酸盐，牛磺酸盐和木质素磺酸盐。 [0224] Suitable anionic SFA include fatty alkali metal, salts (e.g., sodium lauryl sulfate) aliphatic monoesters of sulfuric acid, salts (e.g., sodium dodecylbenzene sulfonate, sulfonated aromatic compounds ten two calcium alkylbenzenesulfonate, butyl and diisopropyl naphthalene sulfonate - and triisopropyl - a mixture of sodium naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g. lauryl ether sulfate -3- sodium), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products of reaction of one or more fatty alcohols and phosphoric acid (predominately mono-esters) or with the reaction product of phosphoric anhydride (mainly bis ester), e.g., the reaction product of lauryl alcohol and tetraphosphoric acid; additionally these can also be ethoxylated), sulfo succinamates, paraffin or olefin sulphonates, taurates and lignosulphonates.

[0225] 适宜的两性型SFA包括甜菜碱、丙酸盐和甘氨酸盐。 [0225] Suitable amphoteric SFA include betaine, propionates and glycinates.

[0226] 适宜的非离子型SFA包括烯基氧化物(如环氧乙烷、氧化丙烯、氧化丁烯或其混合物)与脂肪醇(如油醇或十六烷醇)或烷基酚(如辛基酚、壬基酚或辛基甲酚)的缩合物；衍生于长链脂肪酸或己糖醇酸酐的偏酯；所述偏酯与环氧乙烷的缩合物；嵌段聚合体(包括环氧乙烷和氧化丙烯)；链烷醇酰胺；单一的酯(例如脂肪酸聚乙二醇酯)；氧化胺(例如十二烷基二甲氧化胺)；和卵磷脂。 [0226] Suitable nonionic alkylene oxide comprises SFA (e.g., ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or alkyl phenols (e.g. octyl phenol, nonyl phenol or octyl-cresol) condensates; derived from long chain fatty acids or hexitol anhydrides partial esters; said partial esters with ethylene oxide condensates; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; single esters (e.g., fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithin.

[0227] 适宜的悬浮剂包括亲水胶体(如聚糖、聚乙烯吡咯烷酮或羧甲基纤维素钠)和膨胀粘土(如膨润土或硅镁土)。 [0227] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0228] 式(I)化合物可以通过任何已知的施用杀虫化合物的方法来施用。 Compound [0228] of formula (I) may be administered by any known administration pesticidal compounds. 例如，它可以以已配制的或未配制的形式直接施用于害虫或害虫栖息地(例如害虫栖所，或易受害虫侵害的生长植物)或植物的任一部分，包括叶、茎、枝或根，在播种之前施用于种子或者施用于植物生长或即将生长的其它介质(如叶部周围的土壤、普通土壤、水稻田的水或水耕法栽培系统)，或可以喷射、涂粉、浸溃施用，以乳膏或糊状制剂来施用，以蒸气的方式施用或通过在土壤或水环境中分布或掺入组合物(如颗粒状组合物或以水溶性囊包裹的组合物)的方式施用。 For example, it may be formulated in the form has been formulated or applied directly to the pest or pest habitats (eg pest habitat, or susceptible to the growth of plant pests) or any part of the plant, including the leaves, stems, branches or roots , applied to the seed prior to sowing or applied to the plant growth or is about to grow other media (such as soil surrounding the leaf, ordinary soil, paddy water or hydroponic culture systems), or may be sprayed, dusting, dipping administration, a cream or paste formulation to be administered, as a vapor or applied through distribution manner or incorporated into the composition (e.g. granular composition or a water-soluble pouch composition package) manner in the soil or an aqueous environment administration .

[0229] 也可以将式(I)化合物注入植物中或用电动喷洒技术或其它低容量方法喷洒在植被上，或通过陆上或空中灌溉系统施用。 [0229] The compound may also be injected into plants with an electric spraying techniques or other low volume methods sprayed on vegetation, land or air, or through irrigation systems administration or the formula (I).

[0230]用作水相制剂(水溶液或分散体)的组合物通常以含高比例活性成分的浓缩物形式施用，浓缩物在使用以前加水稀释。 [0230] formulation as aqueous phase (solution or dispersion) of the composition is typically in the form of a concentrate containing a high proportion of the active ingredient is administered, the concentrate is diluted with water before use. 这些浓缩物，包括DC、SC、EC、EW、ME、SG、SP、WP、WG和CS，经常需要经受长期储存，并且经过这种储存之后，加水能形成水剂，该水剂在足够的时间内可保持均匀性，从而使它们能以常规喷洒设备施用。 These concentrates, including DC, SC, EC, EW, ME, SG, SP, WP, WG and CS, often need to withstand long-term storage, and after such storage, plus water forming agent, the agent in sufficient time uniformity can be maintained, so that they can be administered in conventional spray equipment. 依据它们使用的目的，这种水剂可以含有不同量的式(I)化合物(例如0.0001-10%重量)。 Depending on the purpose of their use, which may contain varying amounts of agent of formula (I) compound (e.g., 0.0001% by weight).

[0231 ] 式(I)化合物可与肥料(例如含氮、钾、或磷肥料)混和使用。 Compound [0231] formula (I) can be used with fertilizers (for example nitrogen-, potassium or phosphorous fertilizer) mixed use. 适宜的剂型包括肥料颗粒剂。 Suitable formulations include granules of fertilizer. 混合物适当地包括至多25%重量的式(I)化合物。 The mixture suitably comprises up to 25% by weight of a compound of formula (I). [0232] 因此本发明还提供一种包含肥料和式(I)化合物的肥料组合物。 [0232] Thus the present invention also provides a fertilizer composition comprising a fertilizer and a compound of formula (I) contains.

[0233] 本发明组合物可包括其它具有生物活性的化合物，例如具有杀菌活性或植物生长调节活性、除草、杀虫、杀线虫或杀螨活性的微量元素或化合物。 [0233] The compositions of the invention may include other compounds having biological activity, such as having fungicidal activity or plant growth regulating activity, herbicidal, insecticidal, nematicidal or acaricidal activity of trace elements or compounds.

[0234] 式(I)化合物可以是组合物中的单一活性成分或者它也可是与一种或多种附加的活性成分(如杀虫剂、杀真菌剂、增效剂、除草剂或植物生长调节剂)混和的。 [0234] Formula (I) compound in the composition may be the sole active ingredient or it may also be combined with one or more additional active ingredients (e.g. insecticide, fungicide, synergist, herbicide or plant growth modifiers) blended. 附加活性成分可以是:提供具有更广谱活性或在使用场所持续性增强的组合物；增效或补充(例如通过增加作用速度或克服排斥性)式(I)化合物的活性；或帮助克服或预防对单一组分的抗性。 Additional active ingredient may: provide a broader spectrum of activity or increased persistence properties using the composition; synergistic or complementary (e.g., by increasing the speed of effect or overcoming repellency) of the active compound of formula (I); or help to overcome or prevention of a single component resistance. 具体的附加活性成分依赖于组合物的预想应用。 Specific additional active ingredient depends on the intended application of the composition. 合适的杀虫剂的例子包括: Examples of suitable insecticides include:

[0235] a)拟除虫菊酯类，例如氯菊酯、氯氰菊酯、氰戊菊酯、亚尔发菊酯、溴氢菊酯、三氟氯氰菊酯(尤其是λ-三氟氯氰菊酯)、联苯菊酯、杀螨菊酯、氟氯氰菊酯、七氟菊酯、对鱼安全的拟除虫菊酯(例如苄醚菊酯)、天然除虫菊酯、胺菊酯、S-生物丙烯菊酯、五氟苯菊酯、炔酮菊酯或5-苄基-3-呋喃基甲-(E) -(IR, 3S) -2，2- 二甲基-3- (2-氧硫杂戊环_3_亚基甲基)环丙烷羧酸酯； [0235] a) pyrethroids, such as permethrin, cypermethrin, fenvalerate, permethrin Yar hair, bromine hydrogen permethrin, cyhalothrin (in particular λ- cyhalothrin), bifenthrin , acaricide permethrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example, benzyl permethrin), natural pyrethrin, tetramethrin, S- Bioallethrin pentafluorophenyloxy permethrin, acetylenic ketone permethrin or 5-benzyl-3-furyl methyl - (E) - (IR, 3S) -2,2- dimethyl-3- (2-oxo-thia-dioxolan _3_ subunit A yl) cyclopropanecarboxylate;

[0236] b)有机磷酸盐，例如丙溴磷、虫螨消、乙酰甲胺磷、甲基对硫磷、保棉磷、异吸硫磷I1、庚烯磷、二甲硫吸磷、克线磷、久效磷、丙溴磷、三唑磷、甲胺磷、乐果、磷胺、马拉硫磷、毒死蜱、伏杀磷、特丁甲拌磷、丰索磷、地虫磷、甲拌磷、辛硫磷、甲基嘧啶磷、乙基嘧啶磷、杀螟硫磷、噻唑磷或二嗪磷； [0236] b) organophosphates, such as profenofos, insects and mites elimination, acephate, methyl parathion, azinphos-methyl, parathion different suction I1, heptenophos, dimethyl sulfide phosphorus uptake, g fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, tert phorate, fensulfothion, FONOFOS, phorate, phoxim, pirimiphos-methyl, ethyl pirimiphos, fenitrothion, fosthiazate or diazinon;

[0237] c)氨基甲酸酯(包括芳基氨基甲酸酯)，例如抗蚜威、唑蚜威、除线威、克百威、呋线威、乙硫苯威、涕灭威、thiofurox、丁硫克百威、虫威、仲丁威、残杀威、灭多威或去线威； [0237] c) carbamates (including aryl carbamates) such as pirimicarb, azole pirimicarb, except line Granville, carbofuran, furathiocarb, ethyl benzene, sulfur Granville, aldicarb, thiofurox carbosulfan, insects Granville, Fenobucarb, propoxur, methomyl or to line power;

[0238] d)苯甲酰脲，例如除虫脲、杀铃脲、氟铃脲、氟虫脲或定虫隆； [0238] d) benzoylureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or Chlorfluazuron;

[0239] e)有机锡化合物，例如二环锡、六苯丁锡氧或二唑锡； [0239] e) organic tin compounds such as tin Ring, six Fenbutatin oxygen or oxadiazole tin;

[0240] f)吡唑类，例如吡螨胺和唑螨酯； [0240] f) pyrazoles, such as tebufenpyrad and fenpyroximate;

[0241] g)大环内酯，例如阿维菌素或密比霉素(milbemycins)，例如阿巴美丁、埃玛美丁、苯甲酸酯、伊维菌素、密比霉素、多杀菌素或印苦楝子素； [0241] g) a macrocyclic lactone, such as avermectin or denser than doxorubicin (milbemycins), for example abamectin, Emma Mei Ding, benzoate, ivermectin, denser than vancomycin, spinosad or azadirachtin prime;

[0242] h)激素或信息激素； [0242] h) Hormones or pheromones;

[0243] i)有机氯化合物，例如硫丹、六六六、DDT、氯丹或狄氏剂； [0243] i) organic chlorine compounds, such as endosulfan, BHC, DDT, chlordane or dieldrin;

[0244] j)脒类，例如杀虫脒或双甲脒； [0244] j) amidines, such as chlordimeform or amitraz;

[0245] k)熏蒸剂，例如氯化苦、二氯丙烷、溴甲烷或威百亩； [0245] k) fumigants, such as chloropicrin, dichloropropane, methyl bromide or metam sodium;

[0246] I)氯烟碱基化合物，例如吡虫啉、噻虫啉、啶虫脒、烯啶虫胺或噻虫嗪； [0246] I) chloro nicotinic compounds, such as imidacloprid, thiacloprid, acetamiprid, nitenpyram or thiamethoxam;

[0247] m) 二酰基肼类，例如虫酰肼、环虫酰肼或甲氧虫酰肼； [0247] m) diacylhydrazines class, such as tebufenozide, tebufenozide ring or methoxyfenozide;

[0248] η) 二苯醚类，例如苯虫醚或吡丙醚； [0248] η) diphenyl ethers, such as benzene, ether or pyriproxyfen insects;

[0249] ο)茚虫威； [0249] ο) indoxacarb;

[0250] P)溴虫腈；或 [0250] P) Chlorfenapyr; or

[0251] q)吡蚜酮。 [0251] q) Pymetrozine.

[0252] 除上面所列的主要化学杀虫剂类型之外，如果适于组合物应用的需要，还可在组合物中使用具有特定目的的其它杀虫剂。 [0252] In addition to the main types of chemical pesticides listed above, if needed composition suitable for application, but also the use of other pesticides having a specific purpose in the composition. 例如，可以使用适用特定作物的选择性杀虫剂，例如可在水稻中使用钻心虫特异性杀虫剂(例如杀螟丹)或飞虱特异性杀虫剂(例如稻虱净)。 For example, it can be used by crop-specific selective pesticides, for example, using borer specific insecticides (such as cartap) or planthopper in rice-specific insecticide (such as buprofezin). 或者组合物中也可包括针对特定昆虫类/阶段的特定杀虫剂或杀螨剂(例如杀螨的卵一幼虫剂，例如四螨嗪、氟螨隆、噻螨酮或三氯杀螨砜；杀螨游动剂(acaricidal motilicides),例如三氯杀螨醇或克螨特；杀螨剂，例如溴螨酯或乙酯杀螨醇；或植物生长调节剂，例如伏蚁腙、灭蝇胺、烯虫酯、定虫隆或除虫脲)。 Alternatively the compositions can also include certain insecticides or acaricides (e.g., an egg larvae acaricidal agents, such as clofentezine, fluorine mites long, hexythiazox or tetradifon specific insect / stage ; swimming acaricidal agents (acaricidal motilicides), such as dicofol or propargite; miticide, such as bromopropylate or ethyl alcohol mites; or plant growth regulators, such as hydramethylnon, cyromazine, methoprene ester, Chlorfluazuron or diflubenzuron).

[0253]可包含在本发明组合物中的杀菌剂化合物的例子包括(E)-N-甲基-2-[2-(2，5-二甲基苯氧基甲基)苯基]-2-甲氧基亚氨基乙酰胺(SSF-129)，4-溴-2-氰基-N，N- 二甲基-6-三氟甲基苯并咪唑-1-磺酰胺，α - [N- (3_氯-2，6- 二甲苯基)-2-甲氧基乙酰氨基]-Y-丁内酯，4-氯-2-氰基-N，N-二甲基-5-P-甲苯基咪唑-1-横酸胺(IKF-916, cyamidazosulfamid), 3-5- 二氯-N- (3-氯-1-乙基-1-甲基-2-氧丙基)-4-甲基苯甲酰胺(RH-7281，zoxamide), N-烯丙基-4，5-二甲基-2-三甲硅烷基噻吩-3-甲酰胺(M0N65500)，N_(l_氰基-1，2-二甲基丙基)_2_(2，4-二氯苯氧基)丙酰胺(AC382042)，N-(2-甲氧基_5_吡啶基)-环丙烷甲酰胺，活化酯(CGA245704)，棉铃威，aldimorph,敌菌灵，氧环唑，嘧菌酯，苯霜灵，苯菌灵，双苯三唑醇双苯三唑醇，稻瘟散，糠菌唑，磺酸丁嘧啶，敌菌丹，克菌丹，多菌灵，多菌灵，多菌灵盐酸盐、萎锈灵，环丙酰胺，香芹酮，CGA41396，CGA41397，灭螨猛，百菌清，乙菌利，clozylacon，含铜化合物例如王铜、喹啉铜、硫酸铜、树脂酸铜和波尔多液，霜脲氰，环唑醇，嘧菌环胺，咪菌威，二-2-吡啶基二硫化物1，I' - 二氧化物，抑菌灵，哒菌清，氯硝铵，乙霉威，噁醚唑，双苯唑快，氟嘧菌胺，0，O- 二-异丙基-S-苄基硫代磷酸酯，dimefluazole, dimetconazole,烯酰吗啉，甲菌定，烯唑醇，敌螨普，二噻农，十二烷基二甲氯化铵，吗菌灵，多吗菌灵，doguadine,克痕散,环氧菌唑，乙菌定，(Z)-N-苄基-N-([甲基(甲硫基亚乙基氨基氧羰基)氨基]硫)丙氨酸乙酯，土菌灵，噁唑菌酮，咪唑菌酮(RPA407213 )，氯苯嘧啶醇，唑菌腈，甲呋酰苯胺，环酰菌胺(KBR2738)，拌种咯，苯锈啶，粉锈啉，薯瘟锡，毒菌锡，福美铁，嘧菌腙，氟啶胺，氟咯菌腈，氟酰菌胺，氟亚胺，氟喹唑，氟硅唑，氟酰胺，粉唑醇，灭菌丹，麦穗宁，呋霜灵，呋吡菌胺，双胍盐、已唑醇、羟基异噁唑、噁霉灵，抑霉唑、亚胺唑，双胍辛，双胍辛三乙酸盐，种菌唑，异稻瘟净，异菌脲，异丙菌胺(SZX0722)，氨基甲酸异丙基丁酯，稻瘟灵，春雷霉素，醚菌酯，LY186054, LY211795，LY248908，代森锰锌，代森锰，mefenoxam，嘧菌胺，灭锈胺，甲霜灵，羟菌唑，代森联，代森联锌，苯氧菌胺，腈菌唑，甲基胂酸铁铵，二甲基二硫代氨基甲酸镍，间硝酞异丙酯，氟嘧醇，甲呋酰胺，有机汞化合物，噁酰胺，环氧嘧磺隆，喹菌酮，噁咪唑，氧化萎锈灵，稻痕酯，戍菌唑，纹枯脲，叶枯净，三乙膦酸招，磷酸化合物，苯酞，picoxystrobin(ZA1963)，多氧霉素D，代森联，噻菌灵，丙氯咪，二甲菌核利，霜霉威，丙环唑，甲基代森锌，丙酸，吡菌磷，啶斑肟，甲基嘧菌胺，咯喹酮，氯吡呋醚，硝吡咯菌素，季铵化合物，灭螨猛，苯氧喹啉，五氯硝基苯，氟硅唑(F-155)，五氯酚钠，螺环菌胺，链霉素，硫磺，戊唑醇，叶枯酞，四氯硝基苯，氟醚唑，噻菌灵，thif Iuzamid, 2-(硫代氰基甲硫基)苯并噻唑,福美双，timibenconazole,甲基立枯憐，对甲抑菌灵，三唑酮，三唑醇，triazbutil,咪唑嗪,三环唑，克啉菌，肟菌酯(CGA279202)，嗪氨灵，氟菌唑，灭菌唑，有效霉素A，威百亩，乙烯菌核利，代森锌和福美锌。 Examples [0253] may be included in the compositions of the present invention fungicide compounds include (E) -N- methyl-2- [2- (2,5-dimethylphenoxy) phenyl] - 2-methoxyimino-acetamide (SSF-129), 4- bromo-2-cyano -N, N- dimethyl-6-trifluoromethyl-benzimidazol-1-sulfonamide, α - [ N- (3_-chloro-2,6-dimethylphenyl) -2-methoxy-acetamido] -Y- butyrolactone, 4-chloro-2-cyano -N, N- dimethyl-5- P- acid cross-tolyl-imidazol-1-amine (IKF-916, cyamidazosulfamid), 3-5- dichloro -N- (3- chloro-1-ethyl-1-methyl-2-oxopropyl) - 4- methylbenzamide (RH-7281, zoxamide), N- allyl-4,5-dimethyl-2-trimethylsilyl-yl thiophene-3-carboxamide (M0N65500), N_ (l_-cyano- 1,2-dimethylpropyl) _2_ (2,4-dichlorophenoxy) propionamide (AC382042), N- (2- methoxy _5_ pyridyl) - cyclopropanecarboxamide, activated ester (CGA245704), alanycarb, aldimorph, anilazine, oxygen Propiconazole, azoxystrobin, benalaxyl, benomyl, bitertanol bitertanol, rice blast scattered, bromuconazole, sulfonamide acid butyl pyrimidine, captafol, captan, carbendazim, carbendazim, carbendazim hydrochloride, carboxin, cyproterone amides, carvone, CGA41396, CGA41397, Chinomethionate, chlorothalonil , chlozolinate, clozylacon, copper compounds such as copper king, quinoline, copper sulfate, copper resinate and Bordeaux mixture, cymoxanil, cyproconazole, cyprodinil, climbazole Granville, di-2-pyridyl disulfide 1, I '- dioxide, antibacterial spirit, da clear bacteria, chlorine, ammonium nitrate, diethofencarb, Difenoconazole, difenzoquat, fluorine mepanipyrim, 0, O- two - iso -S- benzyl propyl phosphorothioate, dimefluazole, dimetconazole, dimethomorph, A fungus may be, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, it benomyl , more than you carbendazim, doguadine, g marks scattered, epoxy ipconazole, acetic bacteria fixed, (Z) -N- benzyl -N - ([methyl (methyl ethylidene amino-carbonyl) amino] sulfur ) alanine ethyl ester, etridiazole, famoxadone, fenamidone (RPA407213), fenarimol, azole nitrile, carboxylic acid anilide furosemide, fenhexamid (KBR2738), fenpiclonil, benzene fenpropidin, morpholino rust powder, potato plague tin, tin toadstool, ferbam, azoxystrobin hydrazones, fluazinam, fludioxonil fluorine, fluorine acid bacteria amine fluoride imide, fluquinconazole, Flusilazole, flutolanil , flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, guazatine has Hexaconazole, hydroxyisoxazole, hymexazol, imazalil, imibenconazole, Iminoctadine, biguanide Sheen triacetate, ipconazole, Kitazin, iprodione, iprovalicarb (SZX0722), amino acid isopropyl acetate butyrate, Isoprothiolane, kasugamycin, kresoxim, LY186054, LY211795 , LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil, metalaxyl, hydroxyl ipconazole, metiram, metiram zinc, phenoxy bacteria amine, myclobutanil, methyl ARSACETYL ferric ammonium, dimethyl dithiocarbamate, nickel nitrate between phthalate, isopropyl alcohol Fluoxastrobin, ofurace, organic mercury compounds, evil amides, Oxasulfuron, oxolinic acid, oxpoconazole, Oxidation carboxin, rice marks ester, Shu ipconazole, Rhizoctonia urea, leaf blight net, fosetyl-trick, phosphoric acid compounds, phthalide, picoxystrobin (ZA1963), polyoxin D, metiram, thiabendazole Ling, prochloraz microphone, dimethyl sclerotia Lee, propamocarb, propiconazole, methyl Zineb, propionic acid, phosphorus bacteria topiramate, pyrifenox, methyl mepanipyrim, pyroquilon, clopidogrel furosemide ether, pyrrolnitrin, quaternary ammonium compounds, Chinomethionate, quinoxyfen, quintozene, flusilazole (F-155), sodium pentachlorophenol, spiroxamine, streptomycin, sulfur tebuconazole, tecloftalam, tecnazene, fluorine difenoconazole, thiabendazole, thif Iuzamid, 2- (dithiocyano methylthio) benzothiazole, thiram, timibenconazole, methyl Rhizoctonia pity on tolylfluanid, triadimefon, triadimenol, triazbutil, imidazole, piperazine, tricyclazole, g morpholino bacteria, trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole, effective mold Su A, metam sodium, vinclozolin, zineb and ziram.

[0254] 式(I)化合物可与土壤、泥灰或其它根部介质混和，用以保护植物免受源自种子、土壤或叶子的真菌病害。 Compound [0254] formula (I) can be used with soil, plaster or other rooting media mix to protect plants from fungal diseases from seeds, soil or leaves.

[0255] 在组合物中使用的合适增效剂的例子包括增效醚、增效散、丙基增效散和十二烷基咪唑。 [0255] Examples of suitable synergists for use in the compositions include piperonyl butoxide, efficiency scattered, safroxan and dodecyl imidazole.

[0256] 组合物中包括的合适除草剂和植物生长调节剂取决于预定目标和所需效果。 [0256] Suitable compositions include herbicides and plant growth regulators depends on the intended target and the effect required. [0257] 可包含的水稻选择性除草剂的例子是敌稗。 [0257] rice selective herbicide which may be included is propanil example. 棉花中使用的植物生长调节剂的例子是PIX™。 Examples of the cotton plant growth regulator used is PIX ™.

[0258] 某些混合物可包含显著不同的物理、化学或生物学性质的活性成分，因此它们本身难以形成同一种常规剂型。 [0258] Some mixtures may contain the active ingredient significantly different physical, chemical or biological in nature, and therefore difficult to form their own with a conventional dosage form. 在这些情形下可制备成其它的剂型。 In these circumstances other dosage forms can be prepared. 例如，当一种活性成分是水不溶性固体而另一种活性成分是水不溶性的液体时，可通过将固体活性成分分散成悬浮液(采用类似于SC的制备方法)而将液体活性成分分散成乳化液(采用类似于EW的制备方法)，从而可以将每种活性成分分散在同一连续水相中。 For example, when one active ingredient is a water insoluble solid and the other active ingredient is water-insoluble liquid, it can be prepared by dispersing the solid active ingredient as a suspension (using a preparation analogous SC) but dispersing the liquid active ingredient into emulsion (prepared using a procedure similar to EW's), so that each active ingredient can be dispersed in the same continuous aqueous phase. 所得组合物是悬浮乳状液(SE)制剂。 The resulting composition is a suspension emulsion (SE) formulation.

[0259] 本发明通过下列实施例加以说明: [0259] The present invention is illustrated by the following examples:

[0260] 采用下列参数来获得下列实施例所选化合物的质谱数据: [0260] The following parameters to obtain the following examples of the compound selected mass spectral data:

[0261 ] LCMS: LC5:254nm_ 梯度10%A 至100%B [0261] LCMS: LC5: 254nm_ gradient of 10% A to 100% B

[0262] A=H20+0.01%HC00H [0262] A = H20 + 0.01% HC00H

[0263] B=CH3CN/CH30H+0.01%HC00H 正电喷射150_1000m/z。 [0263] B = CH3CN / CH30H + 0.01% HC00H positive ejection 150_1000m / z.

[0264] 实施例1 [0264] Example 1

[0265] 本实施例说明了2-氯-N_(4-氯-2-{4-[(E)-3_(4-氯苯基)_烯丙基]-哌嗪_1_基}-苯基)-异烟酰胺的制备。 Example [0265] This illustrates the 2-chloro -N_ (4- chloro -2- {4 - [(E) -3_ (4- chlorophenyl) _ allyl] - piperazine _1_ yl} - phenyl) - Preparation of isonicotinamide.

[0266] [0266]

[0267] 步骤A:在队流下将三乙胺(4.2ml)加入到搅拌的2，4-二氯硝基苯(1.9g)和1-叔丁氧羰基-哌嗪(2.2g)的二甲亚砜(18ml)溶液中。 [0267] Step A: Triethylamine team stream (4.2ml) was added to a stirred solution of 2,4-dichloro-nitrobenzene (1.9g) and 1-tert-butoxycarbonyl - piperazine (2.2g) in two methyl sulfoxide (18ml) solution. 将所得溶液在70°C下搅拌48小时，然后冷却至室温。 The resulting solution was stirred for 48 hours at 70 ° C, and then cooled to room temperature. 往其中加水并用乙酸乙酯萃取混合物三次；用硫酸钠干燥合并的有机层并真空浓缩。 Water was added and the mixture was extracted three times with ethyl acetate; the combined organic layers were dried over sodium sulfate and concentrated under vacuum. 硅胶色谱法处理所得残余物(环己烷:乙酸乙酯=8:2)得到4-(5-氯-2-硝基苯基)-哌嗪-1-甲酸特丁基酯(2.6g)，为泡沫状物。 The resulting residue was treated by silica gel chromatography (cyclohexane: ethyl acetate = 8: 2) to give 4- (5-chloro-2-nitrophenyl) - piperazine-1-carboxylic acid tert-butyl ester (2.6g) , as a foam. 1H NMR(400MHz，CDCl3) 1.5 (s，9H)，2.9 (br s, 4H)，3.5 (brs, 4H)，6.9 (d, J=IOHz, 1H)，7.0 (s, 1H)，7.7.(d, J=IOHz, 1H) ; MS (ES+) 242/244 (M+H+-C02-异丁烯)，286/288 (M+H+-异丁烯)。 1H NMR (400MHz, CDCl3) 1.5 (s, 9H), 2.9 (br s, 4H), 3.5 (brs, 4H), 6.9 (d, J = IOHz, 1H), 7.0 (s, 1H), 7.7. ( d, J = IOHz, 1H); MS (ES +) 242/244 (M + H + -C02- isobutene), 286/288 (M + H + - isobutene).

[0268] 步骤B:在60°C下往搅拌的步骤A所获得化合物(2.5g)的乙醇(40ml)和水(30ml)的悬浮液中加入连二亚硫酸钠(7.6g)。 [0268] Step B: To a stirred solution at 60 ° C of the compound obtained in Step A (2.5g) in ethanol (40ml) and water (30ml) was added to a suspension of sodium dithionite (7.6g). 将所得混合物在60°C搅拌I小时，然后在真空下脱去乙醇。 The resulting mixture was stirred at 60 ° C I h, followed by removing the ethanol in vacuo. 用乙酸乙酯萃取悬浮液三次，用硫酸钠干燥合并的有机层并真空浓缩。 The suspension was extracted three times with ethyl acetate, the organic layer was dried over sodium sulfate and concentrated in vacuo. 硅胶色谱法处理所得残余物(环己烷:乙酸乙酯=1:1)得到4- (2-氨基-5-氯苯基)-哌嗪-1-甲酸特丁基酯(1.0g)，为白色晶体。 The resulting residue was treated by silica gel chromatography (cyclohexane: ethyl acetate = 1: 1) to give 4- (2-amino-5-chlorophenyl) - piperazine-1-carboxylic acid tert-butyl ester (1.0g), as white crystals. Mp125-127。 Mp125-127. 。 . ; 1HNMR (400MHz, CDCl3) 1.5(s, 9H), 2.8 (m, 4H),3.5 (m, 4H), 3.9 (s, 2H), 6.6 (d, J=IOHz, 1H), 6.8 (d, J=IOHz, 1H), 6.9 (s, 1H) ;MS (ES+) 212/214 (!+H+-CO2-异丁烯)，256/258 (M+H+-异丁烯)，312/314 (M+H+)。 ; 1HNMR (400MHz, CDCl3) 1.5 (s, 9H), 2.8 (m, 4H), 3.5 (m, 4H), 3.9 (s, 2H), 6.6 (d, J = IOHz, 1H), 6.8 (d, J = IOHz, 1H), 6.9 (s, 1H);! MS (ES +) 212/214 (+ H + -CO2- isobutene), 256/258 (M + H + - isobutene), 312/314 (M + H +) .

[0269] 步骤C:往搅拌的步骤B所获得化合物(1.0g)的二氯甲烷(20ml)溶液中加入三乙胺(2ml);将溶液冷却到0°C并加入2-氯异烟酰氯(1.2g)。 [0269] Step C: To a stirred solution of the compound obtained in Step B (1.0g) in dichloromethane (20ml) added to the solution, triethylamine (2ml); the solution was cooled to 0 ° C and 2-chloro acid chloride (1.2g). 将所得混合物在室温下搅拌12小时，然后倒入水中，用二氯甲烷萃取两次，用硫酸钠干燥合并的有机层并真空浓缩。 The resulting mixture was stirred at room temperature for 12 hours, then poured into water, extracted twice with dichloromethane, the organic layer was dried over sodium sulfate and concentrated in vacuo. 用硅胶色谱法处理残余物(环己烷:乙酸乙酯=7:2)获得4-{5_氯-2-[(2-氯吡啶-4-羰基)_氨基]-苯基}_哌嗪-1-甲酸特丁基酯，用正己烷/乙酸乙酯结晶得到白色晶体(845mg)。 Processing residue was purified by silica gel chromatography (cyclohexane: ethyl acetate = 7: 2) to obtain 4- {5_-chloro-2 - [(2-chloro-4-carbonyl) amino _] - phenyl} piperazine _ l-carboxylic acid tert-butyl ester, n-hexane / ethyl acetate to give white crystals crystallized (845mg). Μ.p.185-189 °C:¾ NMR(400MHz, CDCl3) 1.5 (s, 9H)，2.9 (m, 4H)，3.7 (m, 4Η)，7.2 (d, J=L 5Hz, IH)，7.2 (dd, J=L 5，ΙΟΗζ, IH)，7.6 (d, J=5.5Ηζ, IH)，7.8 (S，IH)，8 Μ.p.185-189 ° C: ¾ NMR (400MHz, CDCl3) 1.5 (s, 9H), 2.9 (m, 4H), 3.7 (m, 4Η), 7.2 (d, J = L 5Hz, IH), 7.2 (dd, J = L 5, ΙΟΗζ, IH), 7.6 (d, J = 5.5Ηζ, IH), 7.8 (S, IH), 8

• 5 (d, J=IOHz, 1Η), 8.63 (d, J=5.5Hz, 1Η), 9.4(s, IH, NH) ; MS (ES+) 351/353 (!+H+-CO2-异丁烯)，395/397 (M+H+-异丁烯)，451/453 (M+H+)。 • 5 (d, J = IOHz, 1Η), 8.63 (d, J = 5.5Hz, 1Η), 9.4 (s, IH, NH); MS (ES +) 351/353 (! + H + -CO2- isobutylene), 395/397 (M + H + - isobutene), 451/453 (M + H +).

[0270] 步骤D:在室温下将步骤C所获得化合物(200mg)的二氯甲烷(IOml)溶液用三氟乙酸(0.3ml)处理48小时。 [0270] Step D: A mixture of the compound of Step C (200mg) in dichloromethane (IOml) obtained was treated 48 hours with trifluoroacetic acid (0.3ml). 将所得混合物用饱和碳酸氢钠水溶液碱化，然后用二氯甲烷萃取两次，用硫酸钠干燥合并的有机层并真空浓缩。 The resulting mixture was basified with saturated aqueous sodium bicarbonate solution, then extracted twice with dichloromethane, the organic layer was dried over sodium sulfate and concentrated in vacuo. 将所得残余物在乙腈(20ml)中溶解，然后加入二异丙基乙胺(0.16ml)和4-氯肉桂酰氯(96mg)。 The resulting residue in acetonitrile (20ml) was dissolved, followed by addition of diisopropylethylamine (0.16ml) and 4-chloro-cinnamoyl chloride (96mg). 将溶液在室温下搅拌50小时,真空脱去溶剂，残余物用硅胶色谱法处理(环己烷:乙酸乙酯=7:2)获得标题产物(162mg)，为黄色固体。 The solution was stirred at room temperature for 50 hours, the solvent removed in vacuo, and the residue was purified by silica gel chromatography (cyclohexane: ethyl acetate = 7: 2) to obtain the title product (162mg), as a yellow solid. Mp129-132。 Mp129-132. 。 . :¾ NMR(400MHz, CDCl3) 2.7 (m, 4H)，2.9 (m, 4H)，3.2 (d, J=9Hz,2H)，6.2 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H)，7.1-7.3 (m, 6H)，7.6 (d, J=5.5Hz, 1H)，7.70(s, 1H)，8.4 (d, J=IOHz, 1H)，8.5 (d, J=5.5Hz, 1H)，9.4 (s, 1H, NH);保留时间HPLC2.46min; MS (ES+) 501/503/505 (M+H+)。 : ¾ NMR (400MHz, CDCl3) 2.7 (m, 4H), 2.9 (m, 4H), 3.2 (d, J = 9Hz, 2H), 6.2 (dt, J = 18, 9Hz, 1H), 6.5 (d, J = 18Hz, 1H), 7.1-7.3 (m, 6H), 7.6 (d, J = 5.5Hz, 1H), 7.70 (s, 1H), 8.4 (d, J = IOHz, 1H), 8.5 (d, J = 5.5Hz, 1H), 9.4 (s, 1H, NH); retention time HPLC2.46min; MS (ES +) 501/503/505 (M + H +).

[0271] 根据类似于实施例1中所描述的方法制备得到下列化合物: [0271] The following compounds were prepared to give a similar manner as described in Example 1 in accordance with:

[0272] [0272]

[0273] [0273]

[0274] [0274]

[0277] 实施例2 [0277] Example 2

[0278] 本实施例说明了2-氯-N- (2- {4- [ (E) _3_ (4_氯苯基)-烯丙基]-哌嗪-1-基}-苯基)-N-甲基-异烟酰胺的制备。 [0278] This example illustrates the preparation of 2-chloro -N- (2- {4- [(E) _3_ (4_ chlorophenyl) - allyl] - piperazin-1-yl} - phenyl) - N- methyl - Preparation of isonicotinamide.

[0279] [0279]

[0280] 在(TC下往氢化钠(50%的油液，24mg)的四氢呋喃悬浮液中加入4_{2_[ (2_氯-吡啶-4-羰基)-氨基]-苯基}-哌嗪-1-甲酸特丁基酯(IOOmg,如实施例1步骤AC中所述方法制备)，并将所得混合物在0°C下搅拌I小时，同时加入碘甲烷(0.03ml)。将反应混合物在室温下搅拌3小时，然后用乙酸乙酯稀释，用水洗涤三次，用硫酸钠干燥并真空浓缩。所得残余物用硅胶色谱法处理(环己烷:乙酸乙酯=7:3)得到4-{2-[(2_氯-吡啶-4-羰基)_甲基-氨基]-苯基}_哌嗪-1-甲酸特丁基酯，为白色晶体。Mp59-61°C I1H NMR(400MHz, CDCl3) 1.5 (s, 9H)，2.2 (m, 2H)，2.8 (m, 2H)，3.4 (m, 2H)，3.4 (s, 3H)，3.5 (m, 2H), 6.7 (m，1H)，6.9 (m, 1H)，7.0-7.3 (m, 4H)，8.1 (m, 1H) ;MS (ES+) 331 (M+H+_C02-异丁烯)，375 (M+矿-异丁烯)，431 (M+H+)。 [0281] 将该化合物根据实施例1步骤D的方法处理获得标题产物，为黄色晶体。Mp117-120°C:¾ NMR(400MHz, CDCl3) 2.4 (m, 2H), 2.5 (m, 2H), 2.6 (m, 2H), 2.9 (m, 2H) ,3.2(m, 2H)，3.5 (s, 3H)，3.5 (m, 2H)，6.2 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H)，6.8 (d, J=9Hz, IH),6.9 (d, J=5Hz, 1H)，7.0-7.3 (m, 6H)，8.1 (d, J=5Hz, 1H);保留时间HPLC2.17min; MS (ES+) 481/483 (M+H+)。 [0280] In (case TC To sodium hydride (50% in oil, 24mg) in tetrahydrofuran was added 2_ 4_ {[(2_ chloro - pyridine-4-carbonyl) - amino] - phenyl} - piperazine 1-carboxylic acid tert-butyl ester (IOOmg, AC prepared as described in example 1, Step embodiment), and the resulting mixture was stirred at 0 ° C under I hour, while adding iodomethane (0.03ml). The reaction mixture stirring at room temperature for 3 hours and then diluted with ethyl acetate, washed three times with water, dried over sodium sulfate and concentrated in vacuo The resultant residue was purified by silica gel chromatography (cyclohexane: ethyl acetate = 7: 3) to give 4- { 2 - [(2_ chloro - pyridine-4-carbonyl) _ methyl - amino] - phenyl} _ piperazine-1-carboxylic acid tert-butyl ester as white crystals .Mp59-61 ° C I1H NMR (400MHz, CDCl3) 1.5 (s, 9H), 2.2 (m, 2H), 2.8 (m, 2H), 3.4 (m, 2H), 3.4 (s, 3H), 3.5 (m, 2H), 6.7 (m, 1H) , 6.9 (m, 1H), 7.0-7.3 (m, 4H), 8.1 (m, 1H); MS (ES +) 331 (M + H + _C02- isobutene), 375 (M + mine - isobutene), 431 (M . + H +) [0281] The title product compound the method of Example 1, Step D according to the process, as yellow crystals .Mp117-120 ° C: ¾ NMR (400MHz, CDCl3) 2.4 (m, 2H), 2.5 (m , 2H), 2.6 (m, 2H), 2.9 (m, 2H), 3.2 (m, 2H), 3.5 (s, 3H), 3.5 (m, 2H), 6.2 (dt, J = 18, 9Hz, 1H ), 6.5 (d, J = 18Hz, 1H), 6.8 (d, J = 9Hz, IH), 6.9 (d, J = 5Hz, 1H), 7.0-7.3 (m, 6H), 8.1 (d, J = 5Hz, 1H); retention time HPLC2.17min; MS (ES +) 481/483 (M + H +).

[0282] 根据类似于实施例2中所描述的方法制备得到下列化合物: [0282] The following compounds were obtained according to the method of Example 2 was prepared in a similar manner as described in:

[0283] [0283]

[0284] 实施例3 [0284] Example 3

[0285] 本实施例说明了2-氯-N-[4-氯-2-(4-甲基-哌嗪_1_基)_苯基]-异烟酰胺 Example [0285] This illustrates the 2-chloro -N- [4- chloro-2- (4-methyl - piperazinyl _1_ yl) _ phenyl] - isonicotinamide

的制备。 Preparation.

[0287] 步骤A:将4-{5-氯-2-[(2-氯吡啶-4-羰基)-氨基]-苯基}_哌嗪-1-甲酸特丁基酯(6.7g，实施例1，步骤C)在二氯甲烷(20ml)中的溶液在室温下用三氟乙酸(IOml)处理20小时。 [0287] Step A: 4- {5-chloro-2 - [(2-chloro-4-carbonyl) - amino] - phenyl} _ piperazine-1-carboxylic acid tert-butyl ester (6.7g, embodiment Example 1, Step C) in dichloromethane (20ml) was treated at room temperature for 20 hours with trifluoroacetic acid (IOml). 减压浓缩溶剂得到2-氯-N-[4-氯-2-(哌嗪-1-基)-苯基]-异烟酰胺三氟醋酸盐(6.9g)，为棕色固体。 The solvent was concentrated under reduced pressure to give 2-chloro -N- [4- chloro-2- (piperazin-1-yl) - phenyl] - isonicotinamide trifluoroacetate (6.9g), as a brown solid. MS (ES+) 351/353 (M+H+)。 MS (ES +) 351/353 (M + H +).

[0288] 步骤B:将步骤A中所获得的产物(300mg)、甲酸(16ml)和37%甲醛水溶液(0.47ml)回流2小时。 [0288] Step B: The product (300mg) obtained in Step A, formic acid (16ml) and 37% aqueous formaldehyde solution (0.47ml) was refluxed for 2 hours. 用水稀释反应混合物，用饱和碳酸氢钠水溶液碱化并用乙酸乙酯萃取。 The reaction mixture was diluted with water, basified with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. 用无水硫酸钠干燥有机层并真空浓缩。 The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. 残余物用硅胶色谱法处理(乙酸乙酯:甲醇=8:2)得到标题产物。 The residue was treated by silica gel chromatography (ethyl acetate: methanol = 8: 2) to give the title product. Mp118-120°C ; 1H NMR(400MHz, CDCl3) 2.4 (s, 3H)，2.7 (m, 2H)，3.0 (m, 4H), 7.2 (m, 2H)，7.6 (d, J=5.0Hz, 1H)，7.7 (s, 1H)，8.4 (d, J=9.0Hz, 1H)，8.5 (d, J=5.0Hz, 1H)，9.4 (br s, 1H) ; MS (ES+) 365/367 (M+H+)。 Mp118-120 ° C; 1H NMR (400MHz, CDCl3) 2.4 (s, 3H), 2.7 (m, 2H), 3.0 (m, 4H), 7.2 (m, 2H), 7.6 (d, J = 5.0Hz, 1H), 7.7 (s, 1H), 8.4 (d, J = 9.0Hz, 1H), 8.5 (d, J = 5.0Hz, 1H), 9.4 (br s, 1H); MS (ES +) 365/367 ( M + H +).

[0289] 实施例4 [0289] Example 4

[0290] 本实施例说明了1-(2-{4-[(E)-3-(4-氯苯基)-烯丙基]-哌嗪-1-基}-4-氟苯 [0290] This example illustrates the 1- (2- {4 - [(E) -3- (4- chlorophenyl) - allyl] - piperazin-1-yl} -4-fluorobenzene

基)-3-(3-甲氧基-丙基)-服的制备。 Yl) -3- (3-methoxy-propyl) - - Preparation of clothes.

[0291] [0291]

[0292] 步骤A:将4-(5-氟-2-硝基苯)_哌嗪-1-甲酸特丁基酯(10g，如实施例1步骤A中所述由2，4- 二氟硝基苯制备)的二氯甲烷(80ml)溶液在室温下用三氟乙酸(23ml)处理24小时。 [0292] Step A: 4- (5-fluoro-2-nitrophenyl) piperazine-1-carboxylic acid _ t-butyl ester (10g, as described in the Example 1, Step A from 2,4-difluoro- nitrobenzene prepared) in dichloromethane (80ml) solution at room temperature (23ml) for 24 hours with trifluoroacetic acid. 真空浓缩反应混合物。 The reaction mixture was concentrated in vacuo. 将所得残余物在乙腈(100ml)中溶解，然后加入二异丙基乙胺(27ml)和4-氯肉桂酰氯(6.8g)。 The resulting residue in acetonitrile (100ml) was dissolved, followed by addition of diisopropylethylamine (27ml) and 4-chloro-cinnamoyl chloride (6.8g). 将溶液在室温下搅拌17小时，真空脱去溶剂，将所得残余物用硅胶色谱法处理(环己烷:乙酸乙酯=1:1)获得1- [ (E) -3- (4-氯-苯基)-烯丙基]-4- (5-氟-2-硝基-苯基)-哌嗪(10.5g) 5¾ NMR (400MHz, CDCl3) 2.7 (t, J=8Hz, 4H) The solution was stirred at room temperature for 17 hours, the solvent removed in vacuo, and the resulting residue was purified by silica gel chromatography (cyclohexane: ethyl acetate = 1: 1) to obtain 1- [(E) -3- (4- chloro- - phenyl) - allyl] -4- (5-fluoro-2-nitro - phenyl) - piperazine (10.5g) 5¾ NMR (400MHz, CDCl3) 2.7 (t, J = 8Hz, 4H)

，3.1 (t, J=8Hz, 4H)，3.2 (d, J=9Hz, 2H)，6.2 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H)，6.6 (dt,J=L 0，7.0Hz, 1H), 6.7 (dd, J=L 0，10Hz, 1H), 7.2-7.3 (m, 4H), 7.8 (d, J=7.0，10.0Hz, 1H) ;MS(ES+) 151/153, 376/378 (M+H+)。 , 3.1 (t, J = 8Hz, 4H), 3.2 (d, J = 9Hz, 2H), 6.2 (dt, J = 18, 9Hz, 1H), 6.5 (d, J = 18Hz, 1H), 6.6 (dt , J = L 0,7.0Hz, 1H), 6.7 (dd, J = L 0,10Hz, 1H), 7.2-7.3 (m, 4H), 7.8 (d, J = 7.0,10.0Hz, 1H); MS (ES +) 151/153, 376/378 (M + H +).

[0293] 步骤B:在60°C下往搅拌的步骤A所获得化合物(8.0g)的乙醇(66ml)和水(80ml)的悬浮液中加入连二亚硫酸钠(Hg)。 [0293] Step B: To a stirred solution at 60 ° C of the compound obtained in Step A (8.0g) in ethanol (66ml) and water (80ml) was added to a suspension of sodium dithionite (Hg). 将所得混合物在60°C搅拌I小时，然后在真空下脱去乙醇。 The resulting mixture was stirred at 60 ° C I h, followed by removing the ethanol in vacuo. 用乙酸乙酯萃取悬浮液三次，用硫酸钠干燥合并的有机层并真空浓缩。 The suspension was extracted three times with ethyl acetate, the organic layer was dried over sodium sulfate and concentrated in vacuo. 将所得残余物过硅胶柱(洗脱液乙酸乙酯)得到1- [ (E) -3- (4-氯-苯基)-烯丙基]-4- (5-氟-2-氨基苯基)-哌嗪(4.1g)。 The resultant residue was purified through silica gel column (eluent ethyl acetate) to give 1- [(E) -3- (4- chloro - phenyl) - allyl] -4- (2-amino-5-fluoro-benzene yl) - piperazine (4.1g). 1H NMR (400MHz, CDCl3) 2.6 (m, 4H), 2.9 (m, 4H), 3.2 (d, J=9Hz, 2H)，3 1H NMR (400MHz, CDCl3) 2.6 (m, 4H), 2.9 (m, 4H), 3.2 (d, J = 9Hz, 2H), 3

• 7 (m, 2H)，6.2 (dt, J=18.9Hz, 1H)，6.5 (d, J=18Hz, 1H)，6.6 (m, 2H)，6.7 (d, J=IOHz, 1H)，7.2-7.3 (m, 4H) ;MS (ES+) 151/153，346/348 (M+H+)。 • 7 (m, 2H), 6.2 (dt, J = 18.9Hz, 1H), 6.5 (d, J = 18Hz, 1H), 6.6 (m, 2H), 6.7 (d, J = IOHz, 1H), 7.2 -7.3 (m, 4H); MS (ES +) 151 / 153,346 / 348 (M + H +).

[0294] 步骤C:在氮气下往搅拌的碳酸二特丁基酯(266mg)的二氯甲烷(4ml)溶液中加入4-二甲氨基吡啶(106mg)的二氯甲烷(4ml)溶液，随后加入步骤B中所获得的产物(300mg)。 [0294] Step C: To a stirred solution under nitrogen of carbonic acid tert-butyl ester (266mg) in dichloromethane (4ml) was added 4-dimethylaminopyridine (106mg) in dichloromethane (4ml) was added, followed The product obtained in Step B was added a (300mg). 在室温下搅拌溶液直至脱气终止。 The solution was stirred at room temperature until the termination degassed. 然后滴加入溶于二氯甲烷(4ml)的3-甲氧丙氨基(155mg)溶液，并将所得溶液在室温下搅拌I小时。 Then dissolved in methylene chloride was added dropwise (4ml) of 3-methoxy-propylamino (155mg) was added and the resulting solution was stirred at room temperature for I h. 减压脱去溶剂，将所得残余物用硅胶色谱法(环己烷:乙酸乙酯=1:9)纯化获得标题化合物(210mg)。 Remove the solvent under reduced pressure, and the resulting residue was purified by silica gel chromatography (cyclohexane: 9: ethyl acetate = 1) to obtain the title compound (210mg) was purified. Mp86-90°C ; 1HNMR (400MHz, CDCl3) 1.8(五重峰，J=7Hz, 2H)，2.6 (m, 4H)，2.9 (m, 4H)，3.2 (d, J=9Hz, 2H)，3.2(s, 3H)，3.3 (q, J=7Hz, 2H)，3.4 (t, J=7Hz, 2H)，5.3 (m, 1H)，6.2 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H), 6.8 (m, 2H), 6.9 (s, 1H), 7.2-7.3 (m, 6H), 7.7 (m, 1H);保留时间HPLCl.93;MS (ES+)372/374，461/463 (M+H+)。 Mp86-90 ° C; 1HNMR (400MHz, CDCl3) 1.8 (quintet, J = 7Hz, 2H), 2.6 (m, 4H), 2.9 (m, 4H), 3.2 (d, J = 9Hz, 2H), 3.2 (s, 3H), 3.3 (q, J = 7Hz, 2H), 3.4 (t, J = 7Hz, 2H), 5.3 (m, 1H), 6.2 (dt, J = 18, 9Hz, 1H), 6.5 (d, J = 18Hz, 1H), 6.8 (m, 2H), 6.9 (s, 1H), 7.2-7.3 (m, 6H), 7.7 (m, 1H); retention time HPLCl.93; MS (ES +) 372 / 374,461 / 463 (M + H +).

[0295] 根据类似于实施例4中所描述的方法制备得到下列化合物: [0295] The following compounds were prepared to give a similar manner as described in Example 4 in accordance with:

[0296] [0296]

[0297] 实施例5 [0297] Example 5

[0298] 本实施例说明了1-(2-{4-[(E)-3-(4-氯苯基)_烯丙基]-哌嗪-1-基}-4-氟苯基)-3-(2-氯噻唑-5-基甲基)-咪唑烷-2-酮的制备。 [0298] This example illustrates the 1- (2- {4 - [(E) -3- (4- chlorophenyl) allyl _] - piperazin-1-yl} -4-fluorophenyl) 3- (2-chloro-thiazol-5-ylmethyl) - imidazolidin-2-one was prepared.

[0299] [0299]

[0300] 步骤A:在O °C下往1- [ (E) -3- (4-氣苯基)-稀丙基]~4~ (5_氣_2_氛基-苯基)-哌嗪(1.0g,实施例3，步骤B)的四氢呋喃(IOml)溶液中加入2-氯乙基异氰酸酯(327mg)并在氮气下于室温搅拌所得溶液18小时。 [0300] Step A: To 1- [(E) -3- (4- gas phenyl) - dilute propyl] at O ​​° C at ~ 4 ~ (5_ gas _2_ atmosphere-phenyl) - - piperazine (1.0g, Example 3, Step B) in tetrahydrofuran (IOml) was added 2-chloro-ethyl isocyanate (327mg) and the resulting solution was stirred under nitrogen at room temperature for 18 hours. 将残余物溶解于最少量的四氢呋喃中，然后将其加入到氢化钠(146mg，50%的油溶液)的四氢呋喃(IOml)悬浮液中。 The residue was dissolved in a minimum amount of tetrahydrofuran, and then added to sodium hydride (146mg, 50% oil solution) in tetrahydrofuran (IOml) suspension. 在室温下搅拌反应混合物3小时，减压浓缩，然后用二乙醚粉化获得1- (2- {4-[ (E) -3- (4-氯苯基)-烯丙基]-哌嗪-1-基}-4_氟-苯基)-咪唑烷-2-酮(677mg)白色晶体。 The reaction mixture was stirred at room temperature for 3 hours, concentrated under reduced pressure, and then pulverized with diethyl ether to obtain 1- (2- {4- [(E) -3- (4- chlorophenyl) - allyl] - piperazine -4_-fluoro-1-yl} - phenyl) - imidazolidin-2-one (677mg) as white crystals. Mp170-172°C ; 1HNMR (400MHz, CDCl3) 2.7 (m, 4H) ,3.11 (m, 4H)，3.26 (d, J=6.8Hz, 2H)，3.63 (t, J=5.7Hz, 2H)，3• 99 (t, J=5.7Hz, 2H)，5.12 (br s, 1H)，6.32 (dt, J=15.6，6.8Hz, 1H)，6.57 (d, J=15.6Hz, 1H)， Mp170-172 ° C; 1HNMR (400MHz, CDCl3) 2.7 (m, 4H), 3.11 (m, 4H), 3.26 (d, J = 6.8Hz, 2H), 3.63 (t, J = 5.7Hz, 2H), 3 • 99 (t, J = 5.7Hz, 2H), 5.12 (br s, 1H), 6.32 (dt, J = 15.6,6.8Hz, 1H), 6.57 (d, J = 15.6Hz, 1H),

6.82 (m, 2H)，7.3-7.4 (m, 4H) ;MS (ES+) 415/417 (M+H+)。 6.82 (m, 2H), 7.3-7.4 (m, 4H); MS (ES +) 415/417 (M + H +).

[0301] 步骤B:在0°C将溶于二甲基乙酰胺(4ml)的步骤A所获产物(250mg)加入到氢化钠(50%的油溶液，29mg)在二甲基乙酰胺(4ml)的悬浮液中，并将所得混合物在0°C搅拌30min，同时加入溶于二甲基乙酰胺(4ml)的C-(2-氯-噻唑_5_基)-甲胺(102mg)。 [0301] Step B: at 0 ° C dissolved in dimethylacetamide (4ml) obtained in Step A product (250mg) was added to sodium hydride (50% in oil solution, 29mg) in dimethyl acetamide ( 4ml) suspension, and the resulting mixture was stirred at 0 ° C 30min, while dissolved in dimethylacetamide (4ml) of C- (2- chloro - thiazol _5_ yl) - methylamine (102mg) . 将反应混合物在室温下搅拌2小时，然后加水猝灭反应，用乙酸乙酯萃取(三次)，用硫酸钠干燥并真空浓缩。 The reaction mixture was stirred at room temperature for 2 hours, then the reaction was quenched with water, extracted with ethyl acetate (three times), dried over sodium sulfate and concentrated in vacuo. 残余物用硅胶色谱法处理(环己烷:乙酸乙酯=1:9)得到标题产物，为黄色固体。 The residue was purified by silica gel chromatography (cyclohexane: ethyl acetate = 1: 9) to give the title product as a yellow solid. Mp72-770C ; 1H NMR (400MHz, CDCl3) 2.7 (m, 4H)，3.0 (m, 4H)，3.2 (d, J=7Hz, 2H)，3.35 (t，J=6Hz, 2H)，3.8 (t, J=6Hz, 2H)，4.5 (s, 2H)，6.3 (dt, J=16.7Hz, 1H)，6.5 (d, J=16Hz, 1H)，6.8(m, 2H)，7.2-7.3 (m, 4H)，7.4 (s, 1H) ; MS (ES+) 546/548 (M+H+)。 Mp72-770C; 1H NMR (400MHz, CDCl3) 2.7 (m, 4H), 3.0 (m, 4H), 3.2 (d, J = 7Hz, 2H), 3.35 (t, J = 6Hz, 2H), 3.8 (t , J = 6Hz, 2H), 4.5 (s, 2H), 6.3 (dt, J = 16.7Hz, 1H), 6.5 (d, J = 16Hz, 1H), 6.8 (m, 2H), 7.2-7.3 (m , 4H), 7.4 (s, 1H); MS (ES +) 546/548 (M + H +).

[0302] 实施例6 [0302] Example 6

[0303] 本实施例说明了2-氯-N- (5-氯-2- {4- [ (E) _3_ (4_三氟甲基-苯基)-烯丙基]-哌嗪-1-基}_吡啶-3-基)_异烟酰胺的制备。 [0303] This example illustrates the preparation of 2-chloro -N- (5- chloro -2- {4- [(E) _3_ (4_ trifluoromethyl - phenyl) - allyl] - piperazin -1 - yl} _ 3-yl) _ Preparation of nicotinamide different.

[0304] [0304]

[0305] 步骤Α:在(TC和队下，将哌嗪(1.38g)加入到搅拌的2，6_ 二氯_3_硝基吡啶(3.0g,根据J.Heterocyclic Chem.1994, 31, 73 制备)和二异丙基乙胺(3.0ml)在二氯甲烧(100ml)中的溶液中。将所得混合物在室温下搅拌2小时然后倒入饱和的碳酸氢钠水溶液中，用二氯甲烷萃取，然后用硫酸钠干燥并真空浓缩。硅胶色谱法处理所得残余物(乙酸乙酯:甲醇=8:2)得到1-(6-氯-3-硝基吡啶-2-基)-哌嗪(2.99g)，为红色固体。Μ.p.50-53 °C ; MS (ES+) 243/245 (M+H")。[0306] 步骤B:将在步骤A中获得的产物(800mg)溶于乙腈(320ml)，然后加入二异丙基乙胺(1.2ml)和4-三氟甲基肉桂酰氯(728mg)。将溶液在室温下搅拌24小时，真空脱去溶剂，将所得残余物用硅胶色谱法处理(环己烷:乙酸乙酯=7:3)获得1-(5-氯-3-硝基-吡啶-2-基)-4-[(E)-3-(4-三氟甲基-苯基)-烯丙基]-哌嗪(0.79g)，为黄色泡沫状物。Mp129-132 0C ; 1H NMR (400MHz, CDCl3) 2.7 (m, 4H)，3.3 (d, J=9Hz, 1H)，3.5 (m, 4H)，6.3 (dt,J=18, 9Hz, I Η)，6.5 (d, J=18Hz, 1H)，7.4 (m, 4H)，8.2 (d, J=2Hz, 1H)，8.3 (d, J=2Hz, 1H) ; MS (ES+) 427/429 (M+H+)。 [0305] Step Α: In (TC and teams, piperazine (1.38g) was added to a stirred solution of dichloro _3_ 2,6_ nitropyridine (3.0g, according to J.Heterocyclic Chem.1994, 31, 73 preparation) and diisopropylethylamine (3.0ml) in methylene burn (100ml) in a solution. The resulting mixture was stirred at room temperature for 2 hours and then poured into a saturated aqueous sodium bicarbonate with methylene chloride extraction, then dried over sodium sulfate and concentrated in vacuo The resultant residue was treated by silica gel chromatography (ethyl acetate: methanol = 8: 2) to give 1- (6-chloro-3-nitro-pyridin-2-yl) - piperazine. . (2.99g), as a red solid .Μ.p.50-53 ° C; MS (ES +) 243/245 (M + H ") [0306] Step B: The product obtained in Step A (800mg) was dissolved in acetonitrile (320ml), followed by addition of diisopropylethylamine (1.2ml) and 4-trifluoromethyl cinnamoyl chloride (728mg). The solution was stirred for 24 hours at room temperature, the solvent removed in vacuo, and the resulting residue was by silica gel chromatography (cyclohexane: ethyl acetate = 7: 3) to obtain 1- (5-chloro-3-nitro - pyridin-2-yl) -4 - [(E) -3- (4- trifluoromethyl - phenyl) - allyl] - piperazine (0.79g), as a yellow foam .Mp129-132 0C; 1H NMR (400MHz, CDCl3) 2.7 (m, 4H), 3.3 (d, J = 9Hz, 1H), 3.5 (m, 4H), 6.3 (dt, J = 18, 9Hz, I Η), 6.5 (d, J = 18Hz, 1H), 7.4 (m, 4H), 8.2 (d, J = 2Hz, 1H), 8.3 (d, J = 2Hz, 1H); MS (ES +) 427/429 (M + H +).

[0307] 步骤C:根据实施例1步骤B和C中所描述的方法对步骤B中所获得的产物(435mg)进行还原和酰化，经过硅胶色谱法(环己烷:乙酸乙酯=7:3)后获得标题产物(185mg)。 [0307] Step C: The method according to 1, step B and C as described in Example The product (435mg) obtained in Step B in reduction and acylation, after silica gel chromatography (cyclohexane: ethyl acetate = 7 the title product (185mg) 3) after: Mp156-159°C ; 1H NMR(400MHz, CDCl3) 2.7 (m, 4H)，3.1 (m, 4H)，3.2 (d, J=9Hz, 2H) Mp156-159 ° C; 1H NMR (400MHz, CDCl3) 2.7 (m, 4H), 3.1 (m, 4H), 3.2 (d, J = 9Hz, 2H)

，6.3 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H)，7.4 (d, J=9Hz, 2H)，7.45 (d, J=9Hz, 2H)，7.5 (d,J=5Hz, 1H)，7.6 (s, 1H)，8.0 (d, J=L 5Hz, 1H)，8.55 (d, J=5Hz, 1H)，8.65 (d, J=L 5Hz, 1H)，8.8(s, 1H，NH) ; HPLC 保留时间2.12min; MS (ES+) 536/538 (M+H+)。 , 6.3 (dt, J = 18, 9Hz, 1H), 6.5 (d, J = 18Hz, 1H), 7.4 (d, J = 9Hz, 2H), 7.45 (d, J = 9Hz, 2H), 7.5 (d , J = 5Hz, 1H), 7.6 (s, 1H), 8.0 (d, J = L 5Hz, 1H), 8.55 (d, J = 5Hz, 1H), 8.65 (d, J = L 5Hz, 1H), 8.8 (s, 1H, NH); HPLC retention time 2.12min; MS (ES +) 536/538 (M + H +).

[0308] 根据类似于实施例6中所描述的方法制备得到下列化合物: [0308] The following compounds were obtained according to the method of Example 6 was prepared in a similar manner as described in:

[0309] [0309]

[0311] 实施例7 [0311] Example 7

[0312] 本实施例说明了2-氯-N- (2-氯-4- {4- [ (E) -3- (4-三氟甲氧基-苯基)-烯丙基]-哌嗪-1-基}-吡啶-5-基)-异烟酰胺的制备。 Example [0312] This illustrates the 2-chloro -N- (2- chloro -4- {4- [(E) -3- (4- trifluoromethoxy-phenyl) - - allyl] - piperazine 1-yl} - yl) - isonicotinamide of preparation.

[0313] [0313]

[0314] 根据在实施例1步骤A中所描述的方法在三乙胺(5.3ml)存在下在二甲亚砜中(20ml)使Ι-t-丁氧羰基-哌嗪(2.36g)与2，4-二氯-嘧啶-5-基胺(2.0g)缩合，获得4-(5-氨基-2-氯-嘧啶-4-基)-哌嗪-1-甲酸特丁基酯(3.4g)，为紫色晶体。 [0314] In the method according to Example 1, Step A as described in triethylamine (5.3ml) in the presence of dimethyl sulfoxide (20ml) in making Ι-t- butoxycarbonyl - piperazine (2.36g) and 2,4-dichloro - pyrimidin-5-ylamine (2.0g) condensation to give 4- (5-Amino-2-chloro - pyrimidin-4-yl) - piperazine-1-carboxylic acid tert-butyl ester (3.4 g), as purple crystals. MS (ES+) 314/316 (M+H+)。 MS (ES +) 314/316 (M + H +). 可根据实施例1步骤C和D中所描述的中间体制备得到标题产物2-氯-N-(2-氯-4-{4-[(E) -3-(4-三氟甲氧基-苯基)-烯丙基]-哌嗪-1-基}-吡啶-5-基)-异烟酰胺(120mg)。 To give the title product was prepared according to Intermediate Example 1, Step C and D in the embodiment described 2-chloro -N- (2- chloro -4- {4 - [(E) -3- (4- trifluoromethoxy - phenyl) - allyl] - piperazin-1-yl} - yl) - isonicotinamide (120mg).

[0315] Μ.ρ.210-211 °C ; 1H NMR (400MHz, CDCl3) 2.5 (m, 4H)，3.1 (d, J=9Hz, 1H)，3.6 (m, 4H) [0315] Μ.ρ.210-211 ° C; 1H NMR (400MHz, CDCl3) 2.5 (m, 4H), 3.1 (d, J = 9Hz, 1H), 3.6 (m, 4H)

，6.1 (dt, J=18, 9Hz, 1H)，6.4 (d, J=18Hz, 1H)，7.1 (d, J=I 1Hz, 2H)，7.3 (d, J=IlHz, 2H), 7.6 (d ，J=5Hz, 1H)，7.7 (s, 1H)，7.8 (s, 1H, NH)，8.4 (s, 1H)，8.5 (d, J=5Hz, 1H) ; MS (ES+) 553/555 (M+ H+)。 , 6.1 (dt, J = 18, 9Hz, 1H), 6.4 (d, J = 18Hz, 1H), 7.1 (d, J = I 1Hz, 2H), 7.3 (d, J = IlHz, 2H), 7.6 ( d, J = 5Hz, 1H), 7.7 (s, 1H), 7.8 (s, 1H, NH), 8.4 (s, 1H), 8.5 (d, J = 5Hz, 1H); MS (ES +) 553/555 (M + H +).

[0316] 根据类似于实施例7中所描述的方法制备得到下列化合物:[0317] [0316] 7 prepared according to the method similar to that described in Example the following compounds: [0317]

[0318] 实施例8 [0318] Example 8

[0319] 本实施例说明了2-氯-N-(5-{4-[(E)-3-(4-氯-苯基)_烯丙基]-哌嗪-1-基}_1，3- 二甲基-1H-吡唑-4-基)_异烟酰胺的制备。 Example [0319] This illustrates the preparation of 2-chloro -N- (5- {4 - [(E) -3- (4- chloro-phenyl) - allyl _] - piperazin-1-yl} _1, -1H- 3-methyl-4-yl) _ Preparation of isonicotinamide.

[0320] [0320]

[0321] 步骤A:在(TC和N2下，用4-氯肉桂酰氯(5g)处理N-BOC-哌嗪(4.3g)和三乙胺(9ml)在二甲亚砜(40ml)中的溶液，并将所得溶液在室温下搅拌18小时，倒入水中，用乙酸乙酯萃取(三次)，用硫酸钠干燥并真空浓缩。将残余物过硅胶柱得到粗4-[(E)-3-(4-氯-苯基)-烯丙基]-哌嗪-1-甲酸特丁基酯。将该化合物溶于二氯甲烷(30ml)并在室温下用三氟乙酸(IOml)处理18小时。浓缩得到1- [ (E) -3- (4-氯苯基)-烯丙基]-哌嗪(5.8g)，其通过质谱和NMR谱来表征。MS (ES+) 151/153 (M-哌嗪)，237/239 (M+H+)。 [0321] Step A: In (TC and N2, using 4-chloro-cinnamoyl chloride (5g) Treatment N-BOC- piperazine (4.3g) and triethylamine (9ml) in dimethyl sulfoxide (40ml) at room solution, and the resulting solution was stirred at room temperature for 18 hours, poured into water, extracted with ethyl acetate (three times), dried over sodium sulfate and concentrated in vacuo and the residue was subjected to silica gel column chromatography to give crude 4 -. [(E) -3 - (4-chloro - phenyl) - allyl] - piperazine-1-carboxylic acid tert-butyl ester This compound was dissolved in dichloromethane (30ml) at room temperature and treated with 18 trifluoroacetic acid (IOml) The hour and concentrated to give 1- [(E) -3- (4- chlorophenyl) - allyl] - piperazine (5.8g), which by mass spectroscopy and NMR spectroscopy to characterize .MS (ES +) 151/153 ( M- piperazine), 237/239 (M + H +).

[0322] 步骤B:根据实施例1步骤A中所描述的方法在三乙胺(3.4ml)存在下在二甲亚砜(20ml)中使步骤A中所获得的产物(3.1g)与5-氯-1，3-二甲基-4-硝基-1H-吡唑(1.5g)缩合获得1-[ (E) -3- (4-氯-苯基)-烯丙基]-4- (2，5- 二甲基-4-硝基-2H-吡唑-3-基)-哌嗪(1.82g),为棕色固体。 [0322] Step B: according to the method of Example 1, Step A as described in triethylamine (3.4ml) in the presence of the product (3.1g) in dimethylsulphoxide (20ml) manipulation obtained in step A and 5 - chloro-1,3-dimethyl-4-nitro -1H- pyrazole (1.5g) condensation of 1- [(E) -3- (4- chloro - phenyl) - allyl] -4 - (2,5-dimethyl-4-nitro -2H- pyrazol-3-yl) - piperazine (1.82g), as a brown solid. 1H NMR(400MHz, CDCl3) 2.4 (s, 3H)，2.6 (m, 4H)，3.2(m, 6H)，3.7 (s, 3H)，6.3 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H)，7.2-7.3 (m, 4H) ; MS (ES+) 151/153，376/378 (M+H+)。 1H NMR (400MHz, CDCl3) 2.4 (s, 3H), 2.6 (m, 4H), 3.2 (m, 6H), 3.7 (s, 3H), 6.3 (dt, J = 18, 9Hz, 1H), 6.5 ( d, J = 18Hz, 1H), 7.2-7.3 (m, 4H); MS (ES +) 151 / 153,376 / 378 (M + H +).

[0323] 步骤C:在室温和氮气下往步骤B中所获得产物(800mg)在四氢呋喃(8ml)和甲醇(8ml)中的溶液中加入一水氯化锡(II) (2.9g)和三水乙酸钠(3.5g)。 [0323] Step C: at room temperature under nitrogen to the product obtained in Step B (800mg) was added tin dichloride monohydrate in tetrahydrofuran (8ml) and methanol (8ml) in a solution (II) (2.9g) and tris aqueous sodium acetate (3.5g). 将所得的混合物在室温下搅拌34小时。 The resulting mixture was stirred at room temperature for 34 hours. 将反应混合物在IM氢氧化钠和乙酸乙酯中分离，搅拌lOmin，分离有机层，用硫酸钠干燥并浓缩，获得1- [ (E) -3- (4-氯苯基)-烯丙基]-4- (2，5- 二甲基-4-氨基-2H-吡唑-3-基)-哌嗪(510mg)，为红色固体。 The reaction mixture was separated with ethyl acetate and IM sodium hydroxide and stirred lOmin, the organic layer was separated, dried over sodium sulfate and concentrated to give 1- [(E) -3- (4- chlorophenyl) - allyl ] -4- (2,5-dimethyl-4-amino -2H- pyrazol-3-yl) - piperazine (510mg), as a red solid. 1H NMR(400MHz, CDCl3) 2.3 (s, 3H) ,2.8(m, 4H)，3.3 (m, 4H)，3.4 (d, J=9Hz, 2H)，3.8 (s, 3H)，6.4 (dt, J=18, 9Hz, 1H)，6.7 (d, J=18Hz, IH),7.3-7.4 (m, 4H) ; MS (ES+) 151/153 (肉桂基)，196 (M_ 肉桂基)，346/348 (M+H+)。 1H NMR (400MHz, CDCl3) 2.3 (s, 3H), 2.8 (m, 4H), 3.3 (m, 4H), 3.4 (d, J = 9Hz, 2H), 3.8 (s, 3H), 6.4 (dt, J = 18, 9Hz, 1H), 6.7 (d, J = 18Hz, IH), 7.3-7.4 (m, 4H); MS (ES +) 151/153 (cinnamyl), 196 (M_ cinnamyl), 346 / 348 (M + H +).

[0324] 步骤D:往搅拌的步骤C所获得化合物(250mg)的二氯甲烷(IOml)溶液中加入三乙胺(0.46ml);将溶液冷却到0°C并加入2-氯异烟酰氯(250mg)。 [0324] Step D: To a stirred solution of the compound obtained in Step C (250mg) in dichloromethane (IOml) was added triethylamine (0.46ml); the solution was cooled to 0 ° C and 2-chloro acid chloride (250mg). 将所得混合物在室温下搅拌12小时，然后倒入水中，用二氯甲烷萃取两次，用硫酸钠干燥合并的有机层并真空浓缩。 The resulting mixture was stirred at room temperature for 12 hours, then poured into water, extracted twice with dichloromethane, the organic layer was dried over sodium sulfate and concentrated in vacuo. 所得残余物用硅胶色谱法(乙酸乙酯:乙醇=9:5)处理得到标题化合物(158mg)。 The resulting residue was purified by silica gel chromatography (ethyl acetate: ethanol = 9: 5) to give the title compound (158mg). Μ.ρ.85-88°C ; 1H NMR (400MHz, CDCl3) 2.0 (s, 3H)，2.52 (br s, 4H)，3.05 (t, J=4.8Hz, 4H)，3.1(d, J=6.8Hz, 2H)，3.58 (s, 3H)，6.13 (dt, J=15.6，6.8Hz, 1H)，6.40 (d, J=15.6Hz, 1H)，7.20 (s,4H)，7.55 (d, J=5.2Hz, 1H)，7.69 (s, 1H)，8.49 (d, J=5.2Hz, 1H);保留时间LCMS2.26min; MS(ES+) 485/487 (M+H+)。 Μ.ρ.85-88 ° C; 1H NMR (400MHz, CDCl3) 2.0 (s, 3H), 2.52 (br s, 4H), 3.05 (t, J = 4.8Hz, 4H), 3.1 (d, J = 6.8Hz, 2H), 3.58 (s, 3H), 6.13 (dt, J = 15.6,6.8Hz, 1H), 6.40 (d, J = 15.6Hz, 1H), 7.20 (s, 4H), 7.55 (d, J = 5.2Hz, 1H), 7.69 (s, 1H), 8.49 (d, J = 5.2Hz, 1H); retention time LCMS2.26min; MS (ES +) 485/487 (M + H +).

[0325] 根据类似于实施例8中所描述的方法制备得到下列化合物: [0325] The following compounds were obtained according to the method of Example 8 was prepared in a similar manner as described in:

[0326] [0326]

[0327] 实施例9 [0327] Example 9

[0328] 本实施例说明了2-氯-N- (2- {4- [ (E) _3_ (4_氯-苯基)-烯丙基]_2_氧-哌嗪-1-基-4-氟-苯基)-异烟酰胺的制备。 [0328] This example illustrates the preparation of 2-chloro -N- (2- {4- [(E) _3_ (4_ chloro - phenyl) - allyl] _2_ oxo - piperazin-1-yl -4 --fluoro-phenyl) - - Preparation of isonicotinamide.

[0329] [0329]

[0330] 步骤A:根据US6433134中描述的方法制备哌嗪酮:在室温下和氮气下往乙二胺(32.85ml)的乙醇(150ml)溶液中滴加在乙醇(50ml)中的氯甲酸乙酯(10g)。 [0330] Step A: Preparation of piperazinone according to the method described in US6433134: and under nitrogen to ethylenediamine (32.85ml) in ethanol (150ml) was added dropwise in ethanol (50ml) at room temperature ethyl chloroformate ester (10g). 将所得溶液在室温下搅拌48小时，然后在30min内滴加入新制的乙酸钠的乙醇溶液(用1.9g钠和90ml乙醇制备)。 The resulting solution was stirred at room temperature for 48 hours, then added dropwise over 30min freshly prepared ethanolic solution of sodium acetate (1.9g prepared sodium and 90ml ethanol). 将溶液在室温下搅拌2小时，Hyflo过滤(用乙醇冲洗)，然后在真空中脱去溶剂和过量的二胺。 The solution was stirred at room temperature for 2 hours, Hyflo filtered (washed with ethanol), followed by removing the solvent and excess diamine in vacuo. 将油状残余物在甲苯(400ml)中回流3小时，轻轻倒出甲苯层并使其与剩下的油分离；将甲苯层在0°c下过夜,过滤固体得到哌嗪酮(3.6g)。 The oily residue was refluxed in toluene (400ml) for 3 hours, the toluene layer was decanted and reacted with the remaining oil separation; toluene layer at 0 ° c overnight, the solid was filtered to give piperazinone (3.6g) . Mp108-109°c。 Mp108-109 ° c.

[0331] 步骤B:将哌嗪酮(3.6g)溶于乙腈(100ml)然后用二异丙基乙胺(9ml)和4-氯肉桂酰氯(6.7g)处理。 [0331] Step B: The piperazinone (3.6g) was dissolved in acetonitrile (100ml) and treated with diisopropylethylamine (9ml) and 4-chloro-cinnamoyl chloride (6.7g). 在室温和氮气下搅拌所得反应混合物48小时。 The resulting reaction mixture was stirred for 48 hours at room temperature under nitrogen. 过滤收集白色沉淀，用冰乙腈洗涤并在真空下干燥(白色固体，4.35g)。 The white precipitate was collected by filtration, washed with ice-acetonitrile and dried under vacuum (white solid, 4.35g). 在真空下浓缩滤液，用乙腈结晶所得残余物(白色晶体，1.4g)。 The filtrate was concentrated in vacuo, the resulting residue was crystallized from acetonitrile (white crystals, 1.4g). Mp129-130°C。 Mp129-130 ° C. 两个部分获得的N_4_[ (E)-3-(4-氯苯基)-烯丙基]-哌嗪-2-酮都展现出令人满意的分析数据=1H NMR(400MHz, CDCl3) 2.63 (t, J=5Hz, 2H) Two portions obtained N_4_ [(E) -3- (4- chlorophenyl) - allyl] - piperazin-2-one are showing satisfactory analytical data = 1H NMR (400MHz, CDCl3) 2.63 (t, J = 5Hz, 2H)

，3.12 (s, 2H)，3.15 (d, J=7Hz, 2H)，3.32 (m, 2H)，6.1 (dt, J=18, 9Hz, 1H)，6.5 (d, J=18Hz, 1H)， , 3.12 (s, 2H), 3.15 (d, J = 7Hz, 2H), 3.32 (m, 2H), 6.1 (dt, J = 18, 9Hz, 1H), 6.5 (d, J = 18Hz, 1H),

7.2-7.3 (m, 4H)。 7.2-7.3 (m, 4H).

[0332] 步骤C:在室温和氮气下往步骤B所获得产物(2.51g)的二甲基甲酰胺(50ml)溶液中加入碳酸钾(3.45g)和2，4- 二氟硝基苯(1.59g)。 [0332] Step C: To a nitrogen gas at room temperature and the product obtained in Step B (2.51g) in dimethylformamide (50ml) was added potassium carbonate (3.45g) and 2,4-difluoro-nitrobenzene ( 1.59g). 将所得的混合物在100°C下搅拌24小时。 The resulting mixture was stirred at 100 ° C for 24 hours. 再次加入碳酸钾(1.4g)和2，4-二氟硝基苯(1.4g)，并将所得混合物在110°C下搅拌48小时。 Again potassium carbonate (1.4g) and 2,4-difluoro-nitrobenzene (1.4g), and the resulting mixture was stirred at 110 ° C for 48 hours. 将反应混合物冷却至室温，倒入水中，用乙酸乙酯萃取三次；用盐水洗涤合并的有机层，干燥(Na2SO4)并真空浓缩。 The reaction mixture was cooled to room temperature, poured into water, and extracted three times with ethyl acetate; combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. 柱色谱法(环己烷/乙酸乙酯=6:4)得到4- [ (E) -3- (4-氯-苯基)-烯丙基]-1-(5-氟-2-硝基苯基)-哌嗪-2-酮(1.9g)，为棕色固体。 Column chromatography (cyclohexane / ethyl acetate = 6: 4) to give 4- [(E) -3- (4- chloro - phenyl) - allyl] -1- (5-fluoro-2-nitro yl-phenyl) - piperazin-2-one (1.9g), as a brown solid. Μ.p.570C ;MS (ES+) 151/153(肉桂基)，390/392 (M+H+)。 Μ.p.570C; MS (ES +) 151/153 (cinnamyl), 390/392 (M + H +).

[0333] 步骤D:往步骤C所获得化合物(389mg)的乙醇(IOml)溶液中加入兰尼镍(50%水悬浮液，200mg);再加入水合肼(0.5ml)，并在室温下搅拌所得反应混合物直至脱气中止(I小时)。 [0333] Step D: The alcohol of Step C (IOml) compound (389mg) obtained was added Raney nickel (50% aqueous suspension, 200mg); was added hydrazine hydrate (0.5ml), and the mixture was stirred at room temperature The resulting reaction mixture was degassed until the suspension (I h). Hyflo过滤反应混合物，真空脱去溶剂，所得残余物用柱色谱法(2.5%的甲醇在乙酸乙酯中的溶液)纯化得到1- (2-氨基-5-氟苯基)-4- [ (E) -3- (4-氯苯基)-烯丙基]-哌嗪-2-酮(162mg)。 Hyflo reaction mixture was filtered, the solvent removed in vacuo, the resulting residue was purified by column chromatography (2.5% methanol in ethyl acetate) to give 1- (2-amino-5-fluorophenyl) -4- [( E) -3- (4- chlorophenyl) - allyl] - piperazin-2-one (162mg). 保留时间LCMS2.8lmin;MS (ES+) 360/362 (M+H+)。 Retention time LCMS2.8lmin; MS (ES +) 360/362 (M + H +).

[0334] 步骤E:往搅拌的步骤D所获得化合物(140mg)的二氯甲烷(10ml)溶液中加入三乙胺(0.14ml);将溶液冷却到0°C并加入2-氯异烟酰氯(200mg)。 [0334] Step E: To a stirred solution of the compound obtained in Step D (140mg) in dichloromethane (10ml) added to the solution, triethylamine (0.14ml); the solution was cooled to 0 ° C and 2-chloro acid chloride (200mg). 将所得混合物在室温下搅拌3小时，然后倒入水中，用二氯甲烷萃取两次，用硫酸钠干燥合并的有机层并真空浓缩。 The resulting mixture was stirred at room temperature for 3 hours, then poured into water, extracted twice with dichloromethane, the organic layer was dried over sodium sulfate and concentrated in vacuo. 所得残余物用硅胶色谱法(乙酸乙酯:环己烷=1:1)处理得到标题化合物(130!^)，为白色粉末。 The resulting residue was purified by silica gel chromatography to give the title compound (130 ^!) (Ethyl acetate: 1: cyclohexane = 1) treatment, as a white powder. Mp75-77 0C ;保留时间LCMS3.46min;MS (ES+) 150/152，499/501 (M+H+)。 Mp75-77 0C; retention time LCMS3.46min; MS (ES +) 150 / 152,499 / 501 (M + H +).

[0335] 实施例10 [0335] Example 10

[0336] 本实施例说明了2-氯-N-(2-{4-[(E)-3-(4-氯-苯基)_烯丙基]-哌嗪-1-基}-4，6- 二氯-苯基)_异烟酰胺的制备。 [0336] This example illustrates the preparation of 2-chloro -N- (2- {4 - [(E) -3- (4- chloro-phenyl) - allyl _] - piperazin-1-yl} -4 , 6-dichloro-phenyl) - nicotinamide preparation _ exclusive.

[0337] [0337]

[0338] 步骤Α:在801:和队下将1，3，5_三氯硝基苯(800mg)和l_t_ 丁氧羰基-哌嗪(790mg)的甲苯(20ml)溶液搅拌15小时。 [0338] Step Α: 801: The next team will 1,3,5_ trichloroethyl and nitrobenzene (800mg) and l_t_ butoxycarbonyl - piperazine (790mg) in toluene (20ml) was stirred for 15 hours. 将反应混合物冷却至室温，使其在水和乙酸乙酯中分离，干燥(Na2SO4)有机层并真空浓缩。 The reaction mixture was cooled to room temperature, allowed to separate in water and ethyl acetate, dried (Na2SO4) organic layer was concentrated in vacuo. 硅胶色谱法处理所得残余物(环己烷:乙酸乙酯=8:2)得到4-(3,5-二氯-2-硝基苯基)-哌嗪-1-甲酸特丁基酯(0.37g)。 The resulting residue was treated by silica gel chromatography (cyclohexane: ethyl acetate = 8: 2) to give 4- (3,5-dichloro-2-nitrophenyl) - piperazine-1-carboxylic acid tert-butyl ester ( 0.37g). 1H NMR(400MHz, CDCl3) 1.5 (s, 9H)，2.9 (m, 4H)，3.5 (m, 4H)，7.0 (d, J=2Hz, 1H)，7.16 (d, J=2Hz, 1H);保留时间HPLC2.33min;MS (ES+) 276/278 (M-BOC)，317/319 (Μ-异丙烯)。 1H NMR (400MHz, CDCl3) 1.5 (s, 9H), 2.9 (m, 4H), 3.5 (m, 4H), 7.0 (d, J = 2Hz, 1H), 7.16 (d, J = 2Hz, 1H); Retention time HPLC2.33min; MS (ES +) 276/278 (M-BOC), 317/319 (Μ- propylene).

[0339]步骤B:如实施例8步骤C和D中所描述的方法用氯化亚锡还原步骤A所获得的产物(200mg)然后用2-氯异烟酸氯酸化，得到4- {2-[ (2-氯-吡啶~4~擬基)-氨基]-3, 5- 二氯-苯基)-哌嗪-1-甲酸特丁基酯(1.04g)。 [0339] Step B: The method as described in Example 8, Step C and D as described in Step A product of stannous chloride reduction obtained (200mg) followed by 2-chloro-isonicotinic acid technology, to give 4- {2 - [(2-chloro - pyridine ~ 4 ~ quasi-yl) - amino] -3, 5- dichloro - phenyl) - piperazine-1-carboxylic acid tert-butyl ester (1.04g). 保留时间HPLC2.05min;MS (ES+) 431/433，485/487/489 (MH+)。 Retention time HPLC2.05min; MS (ES +) 431 / 433,485 / 487/489 (MH +).

[0340] 步骤C:在室温下将步骤C所获得化合物(0.08g)的二氯甲烷(Iml)溶液用三氟乙酸(0.1ml)处理24小时。 [0340] Step C: A solution of the compound of Step C (0.08g) in dichloromethane (Iml) for 24 hours to obtain a solution with trifluoroacetic acid (0.1ml). 真空浓缩反应混合物。 The reaction mixture was concentrated in vacuo. 将所得残余物在乙腈(Iml)中溶解，然后加入二异丙基乙胺(0.15ml)和4-氯肉桂酰氯(0.05g)。 The resulting residue in acetonitrile (Iml) was dissolved, followed by addition of diisopropylethylamine (0.15ml) and 4-chloro-cinnamoyl chloride (0.05g). 将溶液在室温下搅拌24小时,真空脱去溶剂，残余物用硅胶色谱法处理获得标题产物(66mg)，为黄色固体。 The solution was stirred at room temperature for 24 hours, the solvent removed in vacuo, and the residue was purified by silica gel chromatography to obtain the title product (66mg), as a yellow solid. Mp79-800C ; 1HNMR (400MHz, CDCl3) 2.37 (m, 4H)，2.6 (m, 4H)，3.1 (d, J=9Hz, 2H)，6.2 (dt, J=18, 9Hz, 1H)，6.5(d, J=18Hz, 1H)，6.9 (d, J=2Hz, 1H)，7.2-7.3 (m, 5H)，7.5 (s, 1H, NH)，7.6 (d, J=4.5Hz, 1H)，7.7(s, 1H), 8.5 (d, J=5.5Hz, 1H);保留时间HPLCl.44min ；MS (ES+) 535/537/539 (M+H+)。 Mp79-800C; 1HNMR (400MHz, CDCl3) 2.37 (m, 4H), 2.6 (m, 4H), 3.1 (d, J = 9Hz, 2H), 6.2 (dt, J = 18, 9Hz, 1H), 6.5 ( d, J = 18Hz, 1H), 6.9 (d, J = 2Hz, 1H), 7.2-7.3 (m, 5H), 7.5 (s, 1H, NH), 7.6 (d, J = 4.5Hz, 1H), 7.7 (s, 1H), 8.5 (d, J = 5.5Hz, 1H); retention time HPLCl.44min; MS (ES +) 535/537/539 (M + H +).

[0341] 根据类似于实施例10中所描述的方法制备得到下列化合物: [0341] According to the method similar to that described in Example 10 to give the following compounds were prepared:

[0342] [0342]

[0344] 实施例Π [0344] Example Π

[0345] 本实施例说明了式(I)化合物的杀虫/杀昆虫特性。 Example [0345] This illustrates the formula (I) insecticidal compounds / insecticidal properties. [0346] 测试试验如下进行: [0346] Test test performed as follows:

[0347]棉贪夜蛾(Spodoptera littoralis) [0347] Spodoptera littoralis (Spodoptera littoralis)

[0348] 将棉花叶片放置于位于24孔微孔板内的琼脂上并以200ppm的施用量喷洒试验液。 [0348] The cotton leaves placed on 24-well microtiter plate located agar and sprayed with fertilizer 200ppm test solution. 干燥后，用51^幼虫侵害叶片。 After drying, 51 ^ larvae against leaves. 处理3天后(DAT)检测试样的死亡率、驱虫效果、摄食行为和生长调节率。 3 days after treatment (DAT) to detect mortality, repellent effect, feeding behavior and growth adjustment rate of the sample. 下列化合物对棉贪夜蛾产生了至少80%的防治率: The following compounds were produced on Spodoptera littoralis prevention of at least 80%:

[0349] 1-3，1-26，1-29, 1-30, 1-49, 1-52, 1-53, 1-75, 1-417，1-532，1-578，1-785，1-854，1-877，11-49，111-49，V-49, XI1-49, XIV-26, XV-26, XXIV-2, XXIV-46, XXIV-90,XXIV-93,XXIV-94, XXV-26 和XXV-49。 [0349] 1-3,1-26,1-29, 1-30, 1-49, 1-52, 1-53, 1-75, 1-417,1-532,1-578,1-785 , 1-854,1-877,11-49,111-49, V-49, XI1-49, XIV-26, XV-26, XXIV-2, XXIV-46, XXIV-90, XXIV-93, XXIV -94, XXV-26 and XXV-49.

[0350]烟芽夜蛾(Heliothis virescens): [0350] tobacco budworm (Heliothis virescens):

[0351] 将卵(0-24小时龄)放置于位于24孔微孔板内的人工馆料上并用移液管施加200ppm的试验液。 [0351] The eggs (0-24 hours old) were placed on 24-well microtiter plate located artificial museum material and with a pipette 200ppm of application of the test liquid. 培育4天后，检测试样的卵死亡率、幼虫死亡率和生长调节率。 4 days of incubation, the sample is detected for egg mortality, larval mortality and growth regulation rate. 下列化合物对烟芽夜蛾产生了至少80%的防治率: The following compounds produced tobacco budworm prevention of at least 80%:

[0352] 1-3，1-6，1-7，1-26, 1-29, 1-30, 1-47, 1-49, 1-52, 1-53, 1-72, 1-75, 1—417，1-532，1-578，1-785，1-854，1-877，111-49，V-49, XI1-49, XIV-26, XIV-49, XV-26, XV1-26, XVI1-26，XXIV-2, XXIV-46, XXIV-90, XXIV-93, XXIV-94, XXV-2, XXV-26, XXV-49 和XXV-68。 [0352] 1-3,1-6,1-7,1-26, 1-29, 1-30, 1-47, 1-49, 1-52, 1-53, 1-72, 1-75 , 1-417,1-532,1-578,1-785,1-854,1-877,111-49, V-49, XI1-49, XIV-26, XIV-49, XV-26, XV1 -26, XVI1-26, XXIV-2, XXIV-46, XXIV-90, XXIV-93, XXIV-94, XXV-2, XXV-26, XXV-49 and XXV-68.

[0353]小菜蛾(Plutella xylostella): [0353] diamondback moth (Plutella xylostella):

[0354] 将人工饵料放置在24孔微孔板(MTP)内并用移液管施加18.2ppm的试验液。 [0354] The artificial bait is placed in a 24-well microtiter plate (MTP) within and application of the test tube with the pipette solution 18.2ppm. 干燥后，用幼虫(L2)侵害MTP (每孔10-15只)。 After drying, the larvae (L2) against MTP (only 10-15 per well). 培育5天后，检测试样的幼虫死亡率、拒食率和生长调节率。 Cultivation 5 days, testing a sample of larval mortality, poor feeding rate and growth adjustment rate. 下列化合物对小菜蛾产生了至少80%的防治率: The following compounds were produced on the diamondback moth prevention of at least 80%:

[0355] 1-26，1-29，1-30,1-49, 1-417，1-532，1-578，1-785，1-854，1-877，V-49, IX-49, XI1-49，XIV-26, XV-26, XXIV-46, XXIV-90 和XXV-26。 [0355] 1-26,1-29,1-30,1-49, 1-417,1-532,1-578,1-785,1-854,1-877, V-49, IX-49 , XI1-49, XIV-26, XV-26, XXIV-46, XXIV-90 and XXV-26.

[0356]埃及伊蚊(Aedes aegypti): [0356] Aedes aegypti mosquito (Aedes aegypti):

[0357] 将10-15只埃及伊蚊(L2)与养料混合物一起放置于96孔微孔板内。 [0357] The 10-15 only Aedes aegypti (L2) and nutrient mixture to stand together in the 96-well microtiter plate. 将试验液以2ppm的施用量移至孔内。 The test solution was administered amount is moved to 2ppm hole. 2天后，检测昆虫的死亡率和生长抑制率。 Two days later, the detection of insect mortality and growth inhibition rate. 下列化合物对埃及伊蚊产生了至少80%的防治率: The following compounds were produced for Aedes aegypti prevention of at least 80%:

[0358] 1-3，1-26，1-29, 1-30, 1-49, 1-52, 1-53, 1-72, 1-75, 1-76, 111—49，111—118，XIV-26，XV-26, XXIV-2, XXIV-46, XXIV-90, XXIV-93, XXIV-94 和XXV-68。 [0358] 1-3,1-26,1-29, 1-30, 1-49, 1-52, 1-53, 1-72, 1-75, 1-76, 111-49,111-118 , XIV-26, XV-26, XXIV-2, XXIV-46, XXIV-90, XXIV-93, XXIV-94 and XXV-68.

[0359] 桃虫牙(Myzus persicae ): [0359] peach cavities (Myzus persicae):

[0360] 将向日葵叶片放置于位于24孔微孔板内的琼脂上并以200ppm的施用量喷洒试验液。 [0360] The sunflower leaves placed on 24-well microtiter plate located agar and sprayed with fertilizer 200ppm test solution. 干燥后，用混合年龄的蚜虫群侵害叶片。 After drying, the mixed age group against aphids leaves. 经过6DAT培育期后，检测试样的死亡率。 After 6DAT incubation period, the mortality rate of the sample is detected. 下列化合物对烟蚜产生了至少80%的防治率: The following compounds were produced on aphid prevention of at least 80%:

[0361] 1-3，1-26，1-29, 1-26, 1-29, 1-30, 1-49, 1-52, 1-53, 1-72, 1-75,111—49，V-49,XXIV-46, XXIV-90 和XXIV-94。 [0361] 1-3,1-26,1-29, 1-26, 1-29, 1-30, 1-49, 1-52, 1-53, 1-72, 1-75,111-49, V -49, XXIV-46, XXIV-90 and XXIV-94.