CN105431433B - There are two rings or tricyclic heterocyclic with sulfur-bearing substituent for killing harmful organism activity - Google Patents

There are two rings or tricyclic heterocyclic with sulfur-bearing substituent for killing harmful organism activity Download PDF

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CN105431433B
CN105431433B CN201480043333.0A CN201480043333A CN105431433B CN 105431433 B CN105431433 B CN 105431433B CN 201480043333 A CN201480043333 A CN 201480043333A CN 105431433 B CN105431433 B CN 105431433B
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compound
alkyl
trifluoromethyl
spp
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CN105431433A (en
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A·埃德蒙兹
M·米尔巴赫
A·斯托勒
O·罗瑟勒尔
A·布驰赫尔兹
O·F·胡特
A·比格特
R·G·豪尔
D·埃默里
P·J·M·容
吕龙
吴亚明
陈瑞芳
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Syngenta Participations AG
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Priority to CN201710871364.0A priority patent/CN107652292B/en
Priority claimed from PCT/EP2014/062946 external-priority patent/WO2015000715A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems

Abstract

It is being used as insecticide and can be prepared by mode known per se, have two rings or tricyclic heterocyclic with sulfur-bearing substituent for killing harmful organism activity, its stereoisomer and tautomeric form.

Description

There are two rings or tricyclic heterocyclic with sulfur-bearing substituent for killing harmful organism activity
The present invention relates to the sulfur heterocyclic ring derivative with insecticidal activity, be related to for prepare them method, be related to bag Composition containing these compounds and be related to they be used for control animal pest biology (including arthropod and especially The representative of insect or Acarina) purposes.
With kill harmful organism effect heterocyclic compound be known and in such as WO 2009/131237, WO 2011/043404、WO 2011/040629、WO 2010/125985、WO 2012/086848、WO 2013/018928、WO 2013/191113rd, described in WO 2013/180193 and WO 2013/180194.
It has now been discovered that with a variety of new Hete rocyclic derivatives for killing harmful organism characteristic.
Present invention is accordingly directed to the compound with Formula I,
A-B (I),
Wherein A is a group being selected from the group, and the group is by chemical formula A1To A8Composition：
Wherein arrow represents to be attached to group B point；And
B is a group being selected from the group, and the group is by chemical formula B1To B11Composition：
Wherein arrow represents to be attached to group A point；
Wherein
L1It is methylene or a direct key；
V0Nitrogen or CR5；
V1It is nitrogen or CR20；V2It is nitrogen or CR21；V3It is nitrogen or CR22；V4It is nitrogen or CR23；
V5It is nitrogen or CR24；V6It is nitrogen or CR25；V7It is nitrogen or CR26；V8It is nitrogen or CR27；
V9It is nitrogen, or CR28；V10It is nitrogen or CR29；V11It is nitrogen or CR30；
G1It is nitrogen or CR31；
G2It is nitrogen or CR32；
G3It is-NR35, oxygen atom or a sulphur atom；
G4It is nitrogen or CR33；
G5It is nitrogen or CR34；
J1、J2、J35 circle heterocycles are formed together, and the heterocycle can be saturated or unsaturated, comprising being selected from the group One or two atom, the group is made up of nitrogen, oxygen and sulphur, and the substituent that the ring can be selected from the group is monosubstituted or takes more In generation, the group is by C1-C6Alkyl, halogen and/or C1-C6Haloalkyl form, its condition be if the ring include two oxygen atoms or Two sulphur atoms, they are separated by a carbon atom；
R1And R2Same or different and each represent hydrogen, halogen, C1-C6Alkyl or C1-C6Haloalkyl；
R3It is that a substituent that can be selected from the group is monosubstituted or polysubstituted C1-C6Alkyl, C2-C6Alkenyl or C2- C6Alkynyl group, the group is by C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynes Epoxide, C2-C6Halo alkynyloxy group, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6 Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Haloalkyl Carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, cyano group, hydroxyl, halogen, C3-C6Cycloalkyl forms, the C3- C6Cycloalkyl in itself can be by selected from halogen and C1-C3The substituent of alkyl is monosubstituted or polysubstituted；It is and miscellaneous by a 5- or 6- member Cyclic group is monosubstituted or polysubstituted, and the substituent that the heterocyclic group can be selected from the group is monosubstituted or polysubstituted, and the group is by C1- C6Alkyl, C1-C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulphur Alkyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Haloalkyl sulphonyl Base, C2-C6Alkyl-carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, C1-C6Alkyl Amino, C1-C6Haloalkylamino, C2-C8Dialkyl amido, C2-C8Halo dialkyl amido, halogen, cyano group and nitro composition；
Or R3It is-CO2R36、-C(O)R36Or hydrogen；
Or R3It is that the substituent that can be selected from the group is monosubstituted or polysubstituted C3-C6Cycloalkyl, the group is by C1-C6Alkane Base, C1-C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynes Epoxide, C2-C6Halo alkynyloxy group and halogen composition；
Or R3It is that a substituent that can be selected from the group is monosubstituted or polysubstituted 5- or 6- circle heterocycles group, the group By C1-C6Alkyl, C1-C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C1-C6Alkyl alkylthio base, C1-C6Alkyl halide Base sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Haloalkyl sulphur Acyl group, C2-C6Alkyl-carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, C1-C6Alkane Base amino, C1-C6Haloalkylamino, C2-C8Dialkyl amido, C2-C8Halo dialkyl amido, halogen, cyano group and nitro group Into；
R35It is that hydrogen, the substituent that can be selected from the group be monosubstituted or polysubstituted C1-C6Alkyl, the group is by C1-C6Alcoxyl Base, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynyloxy group, C2-C6Halo alkynyloxy group, C1-C6 Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl Sulfonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Alkoxy carbonyl, cyano group, hydroxyl, halogen and C3-C6Ring Alkyl forms, described C3-C6Cycloalkyl in itself can be by selected from halogen and C1-C3The substituent of alkyl is monosubstituted or polysubstituted；Or A kind of its N- oxide；
R4、R5、R20、R21、R22、R23、R24、R25、R26、R27、R28、R29And R30It is same or different, and represents Cyano group, nitro, halogen, hydroxyl, C1-C6Alkenyloxy group, C1-C6- halogenated alkoxy ,-C (O) R36-C(O)R36Or hydrogen；Or
The substituent that can be selected from the group is monosubstituted or polysubstituted C1-C6Alkyl, the group by cyano group, halogen, hydroxyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynyloxy group, C2-C6Acetylenic halide oxygen Base, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy Carbonyl, C2-C6Halo alkoxy carbonyl, cyano group, hydroxyl, halogen and C3-C6Cycloalkyl is formed, and the cycloalkyl in itself can be by The substituent substitution being selected from the group, the group is by halogen and Cl-C3Alkyl forms；Or represent
One substituent that can be selected from the group is monosubstituted or polysubstituted phenyl group, and the group is by C1-C6Alkyl, C1- C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6 Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl Carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, C1-C6Alkyl amino, C1-C6Halogen Substituted alkyl amino, C2-C8Dialkyl amido, C2-C8Halo dialkyl amido, halogen, cyano group and nitro composition；
R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、R17、R18And R19It is same or different, and represents C1-C6Alkyl, C1-C6Haloalkyl or hydrogen, and group CR in addition13R14Can be a carbonyl group C=O；
R31、R32、R33、R34And R40It is same or different, and represents C1-C6Alkyl, C1-C6Haloalkyl ,- OR7、-S(O)nR36、-NR36R37、-CO2R36、-C(O)R36, cyano group, nitro, halogen or hydrogen；
R36And R37Same or different, and represent hydrogen, can be by monosubstituted or polysubstituted selected from following substituent C1-C6Alkyl：C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynyloxy group, C2-C6Halo alkynyloxy group, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Halo Alkyl sulphinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Haloalkyl carbonyl Base, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, cyano group, hydroxyl, halogen and C3-C6Cycloalkyl, wherein the C3-C6 The substituent that cycloalkyl can be selected from the group is monosubstituted or polysubstituted, and the group is by halogen and Cl-C3Alkyl forms；Or
R36And R37It is same or different, and represents
One substituent that can be selected from the group is monosubstituted or polysubstituted phenyl group, and the group is by C1-C6Alkyl, C1- C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6 Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl Carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, C1-C6Alkyl amino, C1-C6Halogen Substituted alkyl amino, C2-C8Dialkyl amido, C2-C8Halo dialkyl amido, halogen, cyano group and nitro composition；
Each m independently represents 0,1 or 2, and n represents 0,1 or 2, and its condition is：
A) at-S (O)nR36In, when n is 0, R36It is hydrogen；
B) if B is B1, then A is and A2、A3And A5Different；
C) if A is A1, then B is and B1、B7、B8、B9And B10Different；
D) if A is A5, then B is and B10Different；
Together with acceptable salt, enantiomter, diastereoisomer, dynamic isomer in agrochemicals, and these The N- oxides of compound.
The compound with Formula I with least one basic center can form for example sour addition with following acid Salt, these acid are：Such as strong inorganic acid (such as mineral acid, such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrogen halogen Acid), strong organic carboxyl acid (such as be unsubstituted or as the C being optionally substituted by halogen1-C4Alkane carboxylic acid, such as acetic acid is (as saturation or insatiable hunger The dicarboxylic acids of sum), such as oxalic acid, malonic acid, butanedioic acid, maleic acid, fumaric acid or phthalic acid (as hydroxycarboxylic acid), such as Ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or as benzoic acid), or organic sulfonic acid (such as be unsubstituted or picture The C being optionally substituted by halogen1-C4Alkane-or aryl sulfonic acid, such as methane-or p-methyl benzenesulfonic acid).Tool with least one acidic-group The compound for having Formula I can be with for example, (such as mineral salt be (as alkali metal or alkali salt, such as sodium with alkali forming salt Salt, sylvite or magnesium salts)), with ammonia or organic amine (as morpholine, piperidines, pyrrolidines, single-, two- or three-Iower-alky amine (such as Ethyl-, diethyl-, triethyl group-or dimethyl propylamine), or single-, two- or trihydroxy-Iower-alky amine is (such as single-, two- Or triethanolamine)) forming salt.
The alkyl occurred in substituent defines can be straight chain or side chain, and be such as methyl, ethyl, positive third Base, isopropyl, normal-butyl, sec-butyl, isobutyl group, the tert-butyl group, amyl group, hexyl, nonyl, decyl and their branched chain isomer Body.Alkoxy, alkenyl and alkynyl group are derived from mentioned alkyl group.Alkenyl and alkynyl group can be single or multiple insatiable hungers Sum.
Halogen is usually fluorine, chlorine, bromine or iodine.Correspondingly, this is also applied for the halogen combined with other implications, such as halo Alkyl or halogenophenyl.
Halogenated alkyl group preferably has a chain length from 1 to 6 carbon atom.Haloalkyl be such as methyl fluoride, Difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2- trifluoroethyls, 2- fluoro ethyls, 2- chloroethyls, The fluoro- 2,2,2- trichloroethyls of pentafluoroethyl group, 1,1- bis-, the fluoro ethyls of 2,2,3,3- tetra- and 2,2,2- trichloroethyls；Preferably three Chloromethyl, difluorochloromethyl, difluoromethyl, trifluoromethyl and dichlorofluoromethyl.
Alkoxy base preferably has one preferably from the chain length of 1 to 6 carbon atom.Alkoxy is, such as methoxy Base, ethyoxyl, propoxyl group, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy and still with point different The amoxy and hexyloxy group of structure；Preferably methoxyl group and ethyoxyl.
Alkoxy carbonyl is, such as methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, positive fourth oxygen Base carbonyl, isobutoxy carbonyl, s-butoxycarbonyl or tert-butoxycarbonyl, preferably methoxycarbonyl or ethoxy carbonyl. Halo alkoxy group preferably has a chain length from 1 to 6 carbon atom.Halogenated alkoxy is, such as fluorine methoxyl group, difluoro Methoxyl group, trifluoromethoxy, 2,2,2- trifluoro ethoxies, 1,1,2,2- tetrafluoros ethyoxyl, 2- fluorine ethyoxyl, 2- chloroethoxies, 2,2- difluoroethoxies and 2,2,2- tri-chloroethoxy bases, preferably difluoro-methoxy, 2- chloroethoxies and trifluoromethoxy.
Alkylthio radicals preferably have a chain length from 1 to 6 carbon atom.Alkylthio group is, such as methyl mercapto, second sulphur Base, rosickyite base, isopropyisulfanyl, positive butylthio, isobutylthio, secondary butylthio or tertiary butylthio, preferably methyl mercapto and ethylmercapto group. Alkyl sulphinyl is, such as methylsulfinyl, ethylsulfinyl, propylsulfenyl base, isopropylsulphinyl, just Butylsulfinyl, isobutyl group sulfinyl, sec-butyl sulfinyl, terf-butylsulfinyl；Preferably methylsulfinyl And ethylsulfinyl.
Alkyl sulphonyl is, such as methyl sulphonyl, ethylsulfonyl, sulfonyl propyl base base, isopropelsulfonyl, positive fourth Base sulfonyl, iso-butylsulfonyl, sec-butylsulfonyl or tert. butylsulfonyl；Preferably methyl sulphonyl or ethyl sulphonyl Base.
Alkylamino is, such as methylamino, ethylamino, n-propylamine base, isopropylamino or isomeric butylamine.Dialkylamino It is, such as dimethylamino, methylethylamine, lignocaine, n-propyl-methylamino, dibutylamino and diisopropylaminoethyl. Preferably there is the alkylamino group from 1 to 4 carbon atom chain length.
Alkoxyalkyl preferably has the chain length of 1 to 6 carbon atom.
Alkoxyalkyl is, such as methoxy, methoxy ethyl, ethoxyl methyl, ethoxyethyl group, positive propoxy Methyl, positive propoxy ethyl, i-propoxymethyl or isopropoxyethyl.
These groups of naphthene base preferably have from 3 to 6 ring carbon atoms, such as cyclopropyl, cyclobutyl, cyclopenta and ring Hexyl.Phenyl, also as a substituent (such as phenoxy group, benzyl, benzyloxy, benzoyl, thiophenyl, phenylalkyl, benzene Epoxide alkyl) part, can be substituted.In this case, these substituents can be in ortho position, meta and/ Or contraposition.Preferable the position of substitution is ortho position and the para postion in ring attachment site.
In the context of the present invention, " single to polysubstituted " during substituent defines is typically meant that, depending on substitution The chemical constitution of base, mono-substituted to seven times substitution, preferably mono-substituted to five times substitution, more preferably mono-, di- or It is trisubstituted.
" 5- circle heterocycles " in the present invention refer to a 5- membered aromatic heterocycles group or 5- member Non-aromatic heterocyclic groups, and " 6- circle heterocycles " refer to a 6- membered aromatic heterocycles group or 6- member Non-aromatic heterocyclic groups.Therefore, " 5- or the 6- in the present invention Circle heterocycles group " refers to a 5- or 6- membered aromatic heterocycle group, or a 5- or 6- member Non-aromatic heterocyclic groups.
" 5- the or 6- circle heterocycles group that can be substituted " in the present invention refers to a heterocyclic group, wherein being attached to one Or one or more hydrogen atoms on multiple carbon atoms, one or more nitrogen-atoms and/or one or more sulphur atoms are optionally Substituted by one or more atoms or group selected from a predefined inventory, wherein the group has predefined clear selected from one Single two or more atoms or group, these atoms or group are same to each other or different to each other.In the background of N atoms or S atom In, it is unsubstituted when it is oxidized with a kind of N oxides of each self-forming or sulfone and sulfoxide, the oxidized analog；So And such a analog is within the scope of the present invention.
The example for the 5- or 6- circle heterocycles groups that can be substituted includes pyrrolidines-l- bases group, 3,3,4,4- tetrafluoro pyrroles Alkane-l- bases group, tetrahydrofuran -2- bases group, piperidinyl group, morpholinyl group, thiomorpholinyl groups etc..
The example for the 5- or 6- membered aromatic heterocycle groups that can be substituted be 2- pyrrole radicals, 2- furanyl groups, 3- furyls, 5- pyrazolyls, 4- pyrazolyls, 1- pyrrole radicals, l- methyl -2- pyrrole radicals, 2- methylsulfanyl-l- pyrrole radicals, 2- methylsulfinyls Base -1- pyrrole radicals, 2- methyl sulphonyl-l- pyrrole radicals, 2- methylamino-l- pyrrolyl groups, 2- dimethylamino-l- pyrroles The bromo- 2- furyls of base group, 5-, 5- nitro-2-furyls group, 5- cyano group -2- furanyl groups, 5- methoxyl group -2- furans Base group, 5- acetyl group -2- furyls, 5- methoxycarbonyl -2- furanyl groups, 2- methyl-3-furyls group, 2,5- bis- Methyl-3-furyl group, 2,4- dimethyl -3- furanyl groups, 5- methyl -2- thienyl groups, 3- methyl -2- thienyls Group, l- methyl -3- trifluoromethyl -5- pyrazolyl groups, 5- chloro- l, 3- dimethyl -4- pyrazolyl groups, pyrazoles-l- base bases Group, the chloro- pyrazoles-l- bases groups of 3-, 3- bromo pyrazoles-l- bases group, 4- chloropyrazole-l- bases group, 4- bromo pyrazoles-l- bases Group, imidazoles-l- bases group, 1,2,4- triazole-l- bases group, 3- chloro- l, 2,4- triazole-l- bases group, 1,2,3,4- tetrazoliums- L- bases group, 1,2,3,5- tetrazolium-l- bases group, 2- thienyl groups, 3- thienyl groups, 3- Trifluoromethyl-1s, 2,4- tri- Azoles-l- bases group, 4- trifluoromethyl pyrazol-l- bases group, pyrazinyl group, 4- pyrimidyl groups, 5- pyrimidyl groups, 2- pyrroles The fluoro- 2- Pyridyl residues of piperidinyl group, 3- Pyridyl residues, 4- Pyridyl residues, 3-, the fluoro- 2- Pyridyl residues of 4-, 5- are fluoro- The fluoro- 2- Pyridyl residues of 2- Pyridyl residues, 6-, 2- pyrimidyl groups, 3- chloro-5-trifluoromethylpyridine -2- bases group, 5- tri- Fluoromethylpyridin -2- base groups etc..
In a preferred embodiment of the invention, R35It is that the substituent that can be selected from the group is monosubstituted or polysubstituted C1-C6Alkyl, the group is by C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynes oxygen Base, C2-C6Halo alkynyloxy group, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Halogen Substituted alkyl sulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Alkoxy carbonyl Base, cyano group, hydroxyl, halogen and C3-C6Cycloalkyl forms, the C3-C6Cycloalkyl in itself can be by selected from halogen and C1-C3Alkyl Substituent is monosubstituted or polysubstituted；A kind of or its N- oxide.
Preferably R4、R5、R20、R21、R22、R23、R24、R25、R26、R27、R28、R29And R30Be it is same or different, And represent cyano group, nitro, halogen, hydroxyl ,-C (O) R36Or hydrogen；Or
The substituent that can be selected from the group is monosubstituted or polysubstituted C1-C6Alkyl, the group by cyano group, halogen, hydroxyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynyloxy group, C2-C6Acetylenic halide oxygen Base, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy Carbonyl, C2-C6Halo alkoxy carbonyl, cyano group, hydroxyl, halogen and C3-C6Cycloalkyl is formed, and the cycloalkyl in itself can be by The substituent substitution being selected from the group, the group is by halogen and Cl-C3Alkyl forms；Or represent
One substituent that can be selected from the group is monosubstituted or polysubstituted phenyl group, and the group is by C1-C6Alkyl, C1- C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C1-C6Alkyl alkylthio base, C1-C6Haloalkyl sulfanyl, C1-C6 Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogenated alkyl sulfonyl, C2-C6Alkyl Carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, C1-C6Alkyl amino, C1-C6Halogen Substituted alkyl amino, C2-C8Dialkyl amido, C2-C8Halo dialkyl amido, halogen, cyano group and nitro composition.
Compound with chemical formula (I) is one by a group selected from group A and a group selected from group B Individual combination is formed.
Therefore, in one embodiment of the invention, should be a group for being selected from A with the compound of chemical formula (I) With any one group selected from group B, such as
A) group A1With a moiety combinations being selected from the group, the group is by group B1To B11Composition；
B) group A2With a moiety combinations being selected from the group, the group is by group B1To B11Composition；
C) group A3With a moiety combinations being selected from the group, the group is by group B1To B11Composition；
D) group A4With a moiety combinations being selected from the group, the group is by group B1To B11Composition；
E) group A5With a moiety combinations being selected from the group, the group is by group B1To B11Composition；
F) group A6With a moiety combinations being selected from the group, the group is by group B1To B11Composition；
G) group A7With a moiety combinations being selected from the group, the group is by group B1To B11Composition；Or
H) group A8With a moiety combinations being selected from the group, the group is by group B1To B11Composition.
Similarly, in another embodiment, should be a group selected from B and choosing with the compound of chemical formula (I) From group A any one group, such as
A) group B1With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
B) group B2With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
C) group B3With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
D) group B4With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
E) group B5With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
F) group B6With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
H) group B7With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
E) group B8With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
F) group B9With a moiety combinations being selected from the group, the group is by group A1To A8Composition；
G) group B10With a moiety combinations being selected from the group, the group is by group A1To A8Composition；Or
H) group B11With a moiety combinations being selected from the group, the group is by group A1To A8Composition.
In a further embodiment, group A is from A1To A8Selected from group Q in greater detail below1To Q11In any It is individual, wherein R1As defined in the first aspect：
The further embodiment of the first aspect is listed in following table Z：
Table Z：Combination for chemical formula (I) A and B
In one embodiment of the invention, a preferable group A is A1、A6Or A4；Especially preferably A1And A6； Particularly A1。
In another preferred embodiment of the invention, a preferable group B is B1、B2、B11、B7、B8、B9、B10、B3 Or B6；Especially preferably B1、B2、B11、B7、B8、B9Or B10, particularly B1、B2、B11、B7、B8Or B9；Such as B1、B2Or B11。
Therefore, chemical formula (I) is preferably made up of group A and B following combination：
In one embodiment of the invention, if B1In V0It is CR5, A is and A1Different.It is preferable to carry out at one In example, B1In V0It is CR5, and A is selected from A2、A3、A4、A5And A6, it is especially selected from A4And A6。
In one embodiment of the invention, for each B, L1It is a direct key.
In another embodiment of the present invention, for each A, R1It is same or different and each represents Hydrogen, halogen, C1-C3Alkyl or C1-C3Haloalkyl；Preferably hydrogen, bromine, chlorine, methyl, difluoromethyl or trifluoromethyl.
In another embodiment of the present invention, for each A, R2It is same or different and each represents Hydrogen, halogen, C1-C3Alkyl or C1-C3Haloalkyl；Preferably hydrogen.
In another embodiment of the present invention, for each B, R3It is same or different and each represents C1-C3Alkyl or C1-C3Haloalkyl；Preferably methyl or ethyl.
In another embodiment of the present invention, for each B, R4It is same or different and each represents Hydrogen or C1-C3Alkyl；Preferably hydrogen or methyl.
Further preferably there is Formula I by what one of 4 above-mentioned " another embodiment " groups combination represented Compound.
In another embodiment of the present invention, for each B, m is same or different and each represented 0th, 1 or 2；Preferably 2.
In another embodiment of the present invention, for each B, R6And R7It is same or different and each Represent C1-C3Alkyl or C1-C3Haloalkyl；Preferably methyl.
In another embodiment of the present invention, for each B, R10And R11It is same or different and every Individual expression hydrogen, C1-C3Alkyl or C1-C3Haloalkyl；Preferably hydrogen or methyl.In a preferred embodiment, R11Be hydrogen simultaneously And R10It is methyl.
In another embodiment of the present invention, for each B, R12、R13And R14It is same or different And each represent hydrogen, C1-C3Alkyl or C1-C3Haloalkyl；Preferably hydrogen or methyl.In a preferred embodiment, R13 And R14Individually hydrogen and R12It is methyl.
In another embodiment of the present invention, for each B, R15、R16、R17And R18It is identical or difference And each represent hydrogen, C1-C3Alkyl or C1-C3Haloalkyl；Preferably hydrogen or methyl.In a preferred embodiment, R15、R16、R17And R18Individually hydrogen.
In another embodiment of the present invention, for each B, R19Be it is same or different and represent hydrogen, C1-C4Alkyl or C1-C4Haloalkyl；Preferably hydrogen or the tert-butyl group.
In another embodiment of the present invention, for each B, V1Be it is same or different and represent CH or N。
In another embodiment of the present invention, for each B, V0Be it is same or different and represent CH or N。
In another embodiment of the present invention, for each B, V2It is same or different and represents R21’, Wherein R21’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl, C1-C3Haloalkyl, Or phenyl or 4- trifluoromethyls, preferably hydrogen, chlorine, bromine or trifluoromethyl.
In another embodiment of the present invention, for each B, V3It is same or different and represents CR22’, wherein R22’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl, preferably hydrogen, chlorine, bromine or trifluoromethyl.
In another embodiment of the present invention, for each B, V4Be it is same or different and represent N or CR23’, wherein R23’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V4Represent N or CH.
In another embodiment of the present invention, for each B, V5Be it is same or different and represent N or CR24’, wherein R24’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V5Represent CH.
In another embodiment of the present invention, for each B, V6Be it is same or different and represent N or CR25’, wherein R25’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V6Represent N or CH.
In another embodiment of the present invention, for each B, V7Be it is same or different and represent N or CR26’, wherein R26’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V7Represent N, CH, C- chlorine, C- bromines or C-CF3。
In another embodiment of the present invention, for each B, V8Be it is same or different and represent N or CR27’, wherein R27’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V8Represent CH.
In another embodiment of the present invention, for each B, V9Be it is same or different and represent N or CR28’, wherein R28’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V9Represent N or CH.
In another embodiment of the present invention, for each B, V10Be it is same or different and represent N or CR29’, wherein R29’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V9Represent N or CH.
In another embodiment of the present invention, for each B, V11Be it is same or different and represent N or CR30’, wherein R30’For each B, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably V9Represent N or CH.
In another embodiment of the present invention, for each A, G1Be it is same or different and represent N or CR31’, wherein R31’For each A, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably G1Represent N or CH.
In another embodiment of the present invention, for each A, G2Be it is same or different and represent N or CR32’, wherein R32’For each A, it is same or different and represents hydrogen, halogen, C1-C3Alkyl or C1-C3Halo Alkyl；Preferably G2Represent N or CH.
In another embodiment of the present invention, for each A, G3Be it is same or different and represent oxygen, Sulphur or NR35’, wherein R35It is N- methyl, for each A, is same or different and represents C1-C3Alkyl or C1-C3 Haloalkyl；Preferably G3Represent oxygen, sulphur or N-CH3。
In another embodiment of the present invention, for each A, G4Be it is same or different and represent N or CR33’, wherein R33’For each A, it is same or different and represents C1-C3Alkyl or C1-C3Haloalkyl；It is excellent Selection of land G4Represent N or N-CH3。
In another embodiment of the present invention, for each A, G5Be it is same or different and represent N or CR34’, wherein R34’For each A, it is same or different and represents hydrogen, C1-C3Alkyl or C1-C3Haloalkyl； Preferably G5Represent N or N-CH3。
In another embodiment of the present invention, on each group A4For, J1It is N.
In another embodiment of the present invention, on each group A4For, J2It is CH, C1-C3Alkyl or C1-C3Halo Alkyl, such as CH, C-CH3Or C-CF3。
In another embodiment of the present invention, on each group A4For, J3It is oxygen or sulphur.
The method according to the invention for preparing the compound with chemical formula (I) is generally by the general of this area Logical technical staff is known or for example in WO 2009/131237, WO 2011/043404, WO 2011/040629, WO 2010/ 125985th, WO 2012/086848, WO 2013/018928, WO 2013/191113, WO 2013/180193 and WO 2013/ What the method described in 180194 was carried out, and it is related to the compound with Formulae II,
(wherein Q is group B1、B2、B3、B4、B5、B6、B7、B8、B9And B11, wherein R3、R4、R6、R7、R8、R9、R10、R11、 R12、R13、R14、R15、R16、R17、R18、R19、V0、V1、V2、V3,V4、V5、V6、V7、V8And L1Be as described in Formula I, and And group B1-B9And B11In arrow show the point being attached in Formulae II on the carbonyl atom of carboxylic group) with change Learn Formula II, IV or V compound；
(wherein R1、R2、G1、G2And G5It is such as described in chemical formula (I) and M1It is oxygen, sulphur or NR35), in one kind The reaction occurred in the presence of dehydrating agent such as polyphosphoric acid at a temperature of 150 DEG C to 200 DEG C, with produce with Formula Ia, Ib and Ic compound, wherein these substituents are as described in for chemical formula (I).
Such process is it is well known that and in such as WO 2011/040629 or (M of WO 20091312371It is Oxygen), WO 2011088990 or Chinese Journal of Inorganic Chemistry (Inorg.Chimica Acta), 358 (9), 2701-2710；2005(M1 It is sulphur) and JACS (J.Am.Chem.Soc.), 132 (5), the 1545-1557, (M of 2010 or WO 20081289681 It is NR35) described in.In scheme 1, this method is outlined for the compound with Formula Ia：
Scheme 1
As that can see in scheme 1, the intermediary of the Ia compound for being formed by having chemical formula VI and send out It is raw.In many cases, it is favourable the compound with chemical formula (I) so to be prepared by this kind of intermediate.In scheme 2 This point is illustrated for the compound with Formula Ia.
Scheme 2.
In scheme 2, by known to persons of ordinary skill in the art and be described in such as tetrahedron (Tetrahedron), 61 (46), 10827-10852, the method in 2005, by the compound with Formulae II, (wherein Q is Activation is the compound with Formulae II a as previously described).Such as wherein X0The compound for being halogen is by catalytic amount DMF in the presence of, in atent solvent such as dichloromethane or THF, the temperature (preferably 25 DEG C) between 20 DEG C to 100 DEG C It is lower to carry out processing formation with such as oxalyl chloride or thionyl chloride.Optionally in a kind of presence of alkali (such as triethylamine or pyridine) Under, form the compound with chemical formula VI with the compound processing IIa with formula iii.Alternately, can by In a kind of atent solvent (such as pyridine or THF), optionally in the presence of a kind of alkali (such as triethylamine), at 50 DEG C -180 At a temperature of between DEG C, with dicyclohexylcarbodiimide (DCC) or 1- ethyls -3- (3- dimethylaminopropyls) carbodiimide (EDC) compound of the processing with Formulae II, to provide species IIa (the wherein X being activated0It is X respectively01And X02) prepare Compound with chemical formula VI.Then, the compound with chemical formula VI being achieved in that can be by a kind of acid catalyst In the presence of (such as methanesulfonic acid or p-methyl benzenesulfonic acid), in a kind of atent solvent (such as the pyridine of N- methylpyrroles), 25 DEG C- Between 180 DEG C at a temperature of (preferably 130 DEG C -170 DEG C), it is dehydrated (such as by heating the compound in microwave) and is turned Turn to the compound with Formula Ia.This kind of method was previously described in WO 2010125985.Alternately, exist In a kind of atent solvent (such as THF), at a temperature of between 25 DEG C -50 DEG C, triphenylphosphine, diisopropyl azo two can be used Compound with chemical formula VI is converted into compound (the wherein M with Formula Ia by carboxylate1It is O).Previous pin This kind of light is described to this kind of conversion and prolongs reaction (Mitsunobu) condition (referring to WO 2009131237).With Formulae II and The application for this kind of method that IIa compound reacts with the compound with Formula I V and V respectively is respectively via centre Body VII and VIII produce compound Ib and Ic.
Alternately, the compound with chemical formula (I) can be by making with Formula I X, X, XI, XII and XIII Compound；
(wherein V0、V1、V2、V3、V4、V5、V6、V7、V8And R4Such as defined for chemical formula (I), and X04It is halogen) Reacted with such as the compound with formula iii, IV and V described in scheme 2 and 3, to provide with following chemistry It is prepared by the compound of formula：XIV、XV、XVI、XVII、XVIII、XIX、XX、XXI、XXII、XXIII、XIV、XV、XVI、XVII、 And XVIII；
(wherein R1、R2、R4、G1、G2、G5、V0、V1、V2、V3、V4、V5、V6、V7、V8、J1、J2And J3It is such as in Formula I Definition, M1It is oxygen, sulphur or NR35, and X04It is halogen).With chemical formula XIV, XV, XVI, XVII, XVIII, XIX, XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII and XXVIII compound can be with the changes with chemical formula XXIX Compound
R3-SH (XXIX)
(wherein R3As described in Formula I), a kind of suitable alkali (such as basic metal carbonate (such as Sodium carbonate and potassium carbonate) or alkalinous metal hydride (such as sodium hydride)) in the presence of, in a kind of suitable solvent, 25 Reacted at a temperature of between DEG C -120 DEG C, with provide with Formula I d, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq and Ir compound：
The example for the solvent for needing to be used in the reaction includes ether, for example, THF, glycol dimethyl ether, t-butyl methyl ether, And the dioxane of Isosorbide-5-Nitrae-, aromatic hydrocarbon such as toluene and dimethylbenzene, nitrile such as acetonitrile.Previously have been described above (as example in WO In 2013018928) similar chemical process.Alternately, the reaction can be in a kind of palladium catalyst (such as three (dibenzylidenes Acetone) two palladiums (0)) in the presence of, in a kind of phosphorus part (such as double diphenylphosphine -9,9- dimethyl xanthenes of 4,5- (xanthphos) in the presence of), in a kind of atent solvent (such as dimethylbenzene), the temperature between 100 DEG C -160 DEG C is (excellent Select 140 DEG C) under carry out, such as by Perry about (Perrio) et al. at tetrahedron (Tetrahedron), 61,5253-5259, Described in 2005.The compound (wherein m is 1 or 2) represented by chemical formula (I) can by oxidation with Formula I d, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq and Ir compound produce.The oxidation reaction is typically a kind of molten Carried out in the presence of agent.The example of solvent for needing to be used in the reaction includes aliphatic halogenated hydrocarbon (such as dichloromethane And chloroform), alcohol (such as methanol and ethanol), acetic acid, water and its mixture.Need the reality of oxidant used in the reaction Example includes sodium metaperiodate and metachloroperbenzoic acid.The amount for the oxidant for needing to be used in the reaction is typically to be rubbed relative to 1 1 to 3 mole of that compound Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq and Ir, preferably 1 to 1.2 Mole, with produce with chemical formula compound (I) (wherein m=1), and preferably relative to 1 mole compound Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq and Ir 2 to 2.2 moles of oxidant (preferably m-chloro peroxide benzene first Acid), to produce the compound (wherein m=2) with chemical formula (I).
(wherein B is B to compound with Formula I10) can be by the compound that makes there is chemical formula XXX：
Q1-X05(XXX),
(wherein Q1It is A1、A2、A3、A4And A8, and X05It is a kind of halogen or a leaving group OSO2R38, and A1、A2、A3、A4And A6In these substituents in arrow show group A attach to substituent X04On point, and wherein R38It is optionally by nitro or C1-C3Alkyl-substituted C1-C6Alkyl, C1-C6Haloalkyl or phenyl) with having chemical formula XXXI compound；
(wherein V9、V10And V11It is as described in Formula I), in a kind of suitable alkali (such as sodium hydride or carbon Sour caesium) in the presence of, in a kind of atent solvent (such as dimethylformamide, the pyridine of N- methylpyrroles or acetonitrile), 20 DEG C- Reacted at a temperature of between 150 DEG C to produce the compound with chemical formula XXXII to prepare：
Alternately, compound with chemical formula XXXII can by make the compound with chemical formula XXX with Chemical formula XXXI compound in a kind of atent solvent (such as dioxane), catalytic amount cuprous iodide and catalytic amount one In the presence of kind diamines (such as N, N- dimethyl-ethylenediamine or the trans-N of racemic, N- dimethyl cyclohexanes diamines), with one kind Temperature (preferably 90 DEG C -110 DEG C) of the alkali (such as potassium carbonate or potassium phosphate) between 50 DEG C -120 DEG C reacts to obtain.This Class reaction has a good precedent in the literature, and at such as Journal of Organic Chemistry (J.Org.Chem.), 68,2609-2617, 2003 and organic bulletin (Org.Letts.), 9,643-646, described in 2007.Compound with chemical formula XXXII can be with A kind of halide reagent (such as phosphoryl chloride phosphorus oxychloride, phosphorus trichloride or phosphorus tribromide, phosphorus pentachloride or phosphorus pentabromide or thionyl chloride), appoint Selection of land reacts in a kind of atent solvent at a temperature of between 25 DEG C -120 DEG C, to provide with chemical formula XXXIII Compound (wherein X06It is halogen)：
Then, the compound with chemical formula XXXIII can use the compound with chemical formula XXIX；
R3-SH (XXIX)
(wherein R3As described in Formula I), a kind of suitable alkali (such as alkaline earth metal hydride, such as Sodium hydride) and a kind of polar non-solute (such as dimethylformamide) in the presence of, the temperature between 25 DEG C -120 DEG C Get off to handle, to provide the compound with Formula I s：
The oxidation of compound is carried out by method known to persons of ordinary skill in the art, such as uses periodic acid Sodium to prepare the compound (wherein m=1) with Formula I t, or the metachloroperbenzoic acid (MCPBA) of at least two equivalents, In a kind of atent solvent (such as dichloromethane), the compound (wherein m=2) with Formula I t is produced.
The synthesis is outlined in scheme 3.
Scheme 3
(wherein A is A to compound with Formula I2And G5It is CR34) subgroup can be by the change with Formula I u Compound represents
Wherein Q is group B1、B2、B3、B4、B5、B6、B7、B8、B9Or B11In one, and R1、R2、G1、G2And G4Be as Described in chemical formula (I), and R34It is C1-C6Alkyl or C1-C6Haloalkyl, can be by making have chemical formula XXXIV's Compound
(wherein R1、R2、G1And G2It is as described in chemical formula (I)) and a kind of compound with chemical formula XXXV
(wherein X07It is a kind of halogen or a leaving group OSO2R38, and Q is as defined above), optionally exist In the presence of a kind of suitable alkali, reacted in a kind of atent solvent to prepare.
A kind of other method of compound of the preparation with Formula I u, which is related to, makes the compound with chemical formula XXXIV With XXXVa compound
In the presence of a kind of lewis acid (such as zinc iodide (II) or trifluoromethayl sulfonic acid indium (III)), a kind of lazy Property solvent (such as chlorobenzene or 1,2, dichloro-benzenes) in, and a kind of copper of catalysis (II) salt (such as acetic acid Cu (II)), in oxygen or big Under gas atmosphere, reacted at the temperature (preferably 110 DEG C -140 DEG C) between 100 DEG C -180 DEG C, there is chemistry to provide Formulas I u compound (wherein R34It is hydrogen).Previously in document (referring to advanced synthesis and catalysis (Adv.Synth.Catal.) 2013,355,1741-1747, and Journal of Organic Chemistry (J.Org.Chem.), 2013,78,12494-12504) described in This kind of reaction.In a kind of polar non-solute (such as acetonitrile or dimethylformamide), at ambient temperature, with a kind of halogen Agent (such as N- chloros succinamide, N- bromosuccinamides or N- iodosuccinamides) halogenation has Formula I u change Compound (wherein R34Hydrogen) produce there is Formula I ucCompound
Wherein Q, R1、R2、G1、G2And G4It is and the X as described in chemical formula (I)15It is halogen.With Formula I uc Compound can be with compound R34-M0(wherein M0A kind of boric acid), reacted in the presence of a kind of palladium catalyst, with to Go out the compound with Formula I u.Work as M0When being a kind of boric acid, the reaction is typically in a kind of alkali (such as potassium carbonate, carbonic acid Caesium or potassium phosphate) in the presence of, in a kind of atent solvent (such as dioxane), optionally in presence of water, use one kind Palladium (0) catalyst (such as four (triphenylphosphines) close palladium) is carried out at a temperature of between 80 DEG C -120 DEG C.This kind of suzuki reaction There is good precedent in the literature, see, for example, Ma Suda (Masuda), straight trip (Naoyuki) et al., WO 2012133607. Compound with chemical formula XXXV and XXXVa can be from the compound with Formulae II for example, by shown in scheme 4 It is prepared by method.
Scheme 4
In scheme 4, by it is known to a person of ordinary skill in the art and be described in such as C. expense in (Ferri), " have Machine synthetic reaction (Reaktionen der Organischen Synthese) ", Georg Thieme Verlag, Stuttgart City, the method in the ff of page 1978,223, with N, when O- dimethyl hydroxyls amine reacts, a kind of acyl group with Formulae II a Halogen is converted into Wei Yin Leibu (Weinreb) acid amides IIb.Then, according to Yin Leibu (Weinreb) method (tetrahedron bulletin (Tetrahedron Letters) 1981,22,3815-3818), make Wei Yin Leibu (Weinreb) acyl with Formulae II b Amine is with having chemical formula R35CH2MgHal RMgBr reaction, to provide the compound with chemical formula XXXVb and XXXVa. Compound with chemical formula XXXVa and XXXVb can also be by using with chemical formula R35CH2MgHal RMgBr processing tool There is Formulae II c nitrile compound (wherein Q is as described in Formula I), subsequent sour water solution is (such as in C. takes (Ferri), " organic synthesis (Reaktionen der Organischen Synthese) ", Georg Thieme Verlag, city of Stuttgart, described in the ff of page 1978,223) prepare.
The mixture of such as bromine and hydrobromic acid in acetic acid can be used (such as in phosphorus, sulphur and silicon and coherent element (Phosphorus, Sulfur and Silicon and the Related Elements), 2013,188 (12), 1835- Described in 1844) or with such as copper bromide (II), in a kind of atent solvent (such as chloroform, ethyl acetate etc.) (such as in medicine Thing The Chemicals (J.Med.Chem.), 2013,56 (1), described in 84-96) in by with chemical formula XXXVa and XXXVb Halogenations are the compound with chemical formula XXXV.Alternately, there is chemical formula XXXV compound (wherein R35It is Hydrogen) it can be handled simultaneously with diazomethane or trimethylsilyldiazomwhiche whiche by a kind of atent solvent (such as diethyl ether) And then handled with a kind of halogen acids (such as hydrobromic acid or hydrochloric acid), directly prepared from the compound with Formulae II a.This Class method is it is well known that for example, see European pharmaceutical chemistry magazine (Eu.J.Med.Chem.) 1987,22 in the literature (5), 457-62 and WO 2009010455.
In a similar fashion, there is Formula I uaCompound
(wherein R1、G1、G2It is and the G as described in chemical formula (I)5It is CR34) can be by making with chemical formula (XXXIVa) compound,
(wherein R1、G1、G2It is as described in chemical formula (I)) with having chemical formula XXXV or XXXVa compounds As react and prepared with preparing the compound with Formula I u.It would be recognized by those skilled in the art that with chemistry Formulas I ubCompound
Similarly can by make as described above compound with chemical formula XXXIVb with chemical formula XXXV or XXXVa compound (wherein G5It is CR34) react to prepare.
(wherein A is A to compound with Formula I2And G5Nitrogen) subgroup can be by the chemical combination with Formula I v Thing represents；
(wherein Q is group B1、B2、B3、B4、B5、B6、B7、B8、B9Or B11In one, and R1、R2、G1、G2And G4It is As described in Formula I), can be by the compound that makes there is chemical formula XXXVI；
(wherein R1、R2、G1And G2It is and the wherein X as described in chemical formula (I)08 -It is chemical formula OSO2R38Halogen Compound ion or anion) and a kind of compound with Formulae II a
(wherein X0It is a kind of halogen and Q is as defined above), optionally in the presence of a kind of suitable alkali, Reacted in a kind of atent solvent to prepare.
The compound with chemical formula XXXIV above can be by amino dehalogenation, by making with chemical formula XXXVII compound；
(wherein R1、R2、G1And G2It is and the wherein X as described in chemical formula (I)09A kind of halogen or one from Remove group OSO2R38) reacted preparation with the ammonia (gaseous or water-based) as nucleopilic reagent.Can be a kind of appropriate In atent solvent, the amount or pole excess of ammonia of equimolar amounts are used optionally in pressurizing vessel.The reaction can be at 0 and 200 DEG C Between temperature, optionally to be carried out under microwave irradiation.Ammonia equivalent, such as ammonium hydroxide NH4OH, ammonium acetate can also be used NH4OAc, ammonium carbonate (NH4) 2CO3 are as nitrogen source.
Compound with chemical formula XXXVII can be by making the compound with chemical formula XXXVIII
(wherein R1、R2、G1And G2It is as described in chemical formula (I)), in a kind of atent solvent, with reagent for example Phosphoryl chloride phosphorus oxychloride, phosphorus trichloride or phosphorus tribromide, phosphorus pentachloride or phosphorus pentabromide react to prepare.
Compound with chemical formula XXVIII is known in the literature.For example, the chemical combination with chemical formula XXXVIII Thing (wherein G2It is nitrogen-atoms and G1It is CR31, and wherein R1And R2It is as described in Formula I) in EP 1371638 In be it is known or can with analogy its preparation.
Compound with chemical formula XXXVI can be by N- aminations, by making the above have chemical formula XXXIV change Compound and the O- trimethylbenzenesulfonyls azanol (O-mesitylenesulfonylhydroxylamine) as amination reagent (MSH) reacted to prepare, such as by such as Y. Tian Cun (Tamura) et al., heterocyclic chemistry magazine (J.Heterocyclic Chem.) described in 1975,12,107-110.It it is known that the form that MSH is in its precursor is its acetyl-hydroxamic acid ethyl ester；Use-case Such as the perchloric acid HClO in tetrahydrofuran4Amination reagent MSH needed for the pretreatment release of progress.O- trimethylbenzenesulfonyl hydroxyls Amine (O-mesitylenesulfonyl-hydroxylamine) and the amination reagent of correlation are at Y. Tian Cun (Tamura) Et al., synthesize (Synthesis), 1-17, summarized in 1977.
(wherein A is A to compound with Formula I3And G5Nitrogen) subgroup can be by the chemical combination with Formula I w Thing represents
Wherein Q is group B1、B2、B3、B4、B5、B6、B7、B8、B9Or B11In one, and wherein R1、R2、G1、G2And G4 It is as described in Formula I.
Then, G is worked as4It is CR33When, the compound with Formula I w can be by making the compound with chemical formula XXXIX
(wherein R1、R2、G1And G2It is as described in chemical formula (I)) and a kind of compound with chemical formula XL
(wherein X10It is a kind of halogen or a leaving group OSO2R38, and Q is as defined above), optionally exist In the presence of a kind of suitable alkali, reacted in a kind of atent solvent to prepare.
Alternately, G is worked as4When being nitrogen, the compound with Formula I w can be by making the compound with chemical formula XLI
(wherein R1、R2、G1And G2It is and the wherein X as described in chemical formula (I)11 -It is chemical formula OSO2R38Halogen Compound ion or anion) and a kind of compound with Formulae II a
(wherein X0It is a kind of halogen and Q is as defined above), optionally in the presence of a kind of suitable alkali, Reacted in a kind of atent solvent to prepare.
The compound with chemical formula XXXIX above can be by amino dehalogenation, by making with chemical formula XLII compound
(wherein R1、R2、G1And G2It is and the wherein X as described in chemical formula (I)12A kind of halogen or one from Remove group OSO2R38) reacted with the ammonia (gaseous or water-based) as nucleopilic reagent to prepare.Can be a kind of appropriate Atent solvent in, optionally in pressurizing vessel use equimolar amounts amount or pole excess of ammonia.The reaction can be in 0 and 200 Temperature between DEG C, optionally to be carried out under microwave irradiation.Ammonia equivalent, such as ammonium hydroxide NH can also be used4OH, acetic acid Ammonium NH4OAc and ammonium carbonate (NH4)2CO3As nitrogen source.
Compound with chemical formula XLII can be by making the compound with chemical formula XLIII
(wherein R1、R2、G1And G2It is as described in chemical formula (I)), in a kind of atent solvent, with reagent for example Phosphoryl chloride phosphorus oxychloride, phosphorus trichloride or phosphorus tribromide, phosphorus pentachloride or phosphorus pentabromide or thionyl chloride react to prepare.
Compound with chemical formula XL for example analogy EP 1371638 can be prepared.
Compound with chemical formula XLI can be by N- aminations, by making the above have chemical formula XXXIX chemical combination Thing and the O- trimethylbenzenesulfonyls azanol (O-mesitylenesulfonylhydroxylamine) as amination reagent (MSH) or a kind of its equivalent reacts to prepare, as described in previously for compound of the preparation with chemical formula XXXVI 's.
(wherein A is A to compound with Formula I7And G5And G4Both nitrogen) subgroup can be by with chemistry Formulas I x compound represents
Wherein Q is group B1、B2、B3、B4、B5、B6、B7、B8、B9Or B11In one, and wherein R1、R2、G1And G2It is As described in Formula I.
Compound with Formula I c can be by making the compound with chemical formula XLIV
(wherein R1、R2、G1And G2It is as described in chemical formula (I)) and a kind of compound with chemical formula XLV
X13- Q (XLV),
(wherein X13It is a kind of halogen or a leaving group OSO2R38, and Q is wherein group as defined above B1、B2、B3、B4、B5、B6、B7、B8、B9Or B11In arrow show substituent X13Attachment point), optionally a kind of suitable In the presence of alkali, the analogy such as WO 10/038081 in a kind of atent solvent (such as sodium hydride in dimethylformamide) React to prepare.
Alternately, compound with Formula I x can by make the compound with chemical formula XLIV with chemical Formula X LV compound is reacted under the conditions of the N- arylations of palladium chtalyst to prepare, such as example in S.L. Buchwalds (Buchwald) et al., German applied chemistry (Angew.Chem.Int.Ed.), 50,8944-8947, described in 2011.
The compound with chemical formula XLIV above can be by diazotization, by by with chemical formula XLVI's Compound
(wherein R1、R2、G1And G2It is as described in Formula I) with the natrium nitrosum in water and halogen acids or in nothing With a kind of alkyl nitrite (such as nitrite tert-butyl or isoamyl nitrite) under water condition, optionally in a kind of sour (example Such as acetic acid) in the presence of, in a kind of atent solvent (such as tetrahydrofuran), handled at a temperature of between 0 and 130 DEG C To prepare.Can be in figure Renyi (Torrini) et al., heterocyclic chemistry magazine (J.Heterocyclic Chem.), 23,1459- Find to be related to a representative instance of isoamyl nitrite and acetic acid in the tetrahydrofuran of backflow in 1463,1986.
Compound (wherein R with chemical formula (I)21It is C1-C6Alkenyloxy group ,-C (O) R36) can be as shown in scheme 5 Carry out prepare, scheme 5 is to be directed to group A1-B1Illustrate：
Scheme 5.
In scheme 5, there is chemical formula XLVII compound (wherein R1、R2、G1、G2、L1、R3、R4、V1And V0It is as right In described in chemical formula (I), and X14It is halogen (preferably bromine)) with having chemical formula XLVIII compound (wherein R39 Being can be by selected from following substituent is monosubstituted or polysubstituted C1-C5Alkyl：C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2- C6Alkenyloxy group, C2-C6Halo alkenyloxy group, C2-C6Alkynyloxy group, C2-C6Halo alkynyloxy group, C1-C6Alkyl alkylthio base, C1-C6Alkyl halide Base sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Haloalkyl sulphur Acyl group, C2-C6Alkyl-carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halo alkoxy carbonyl, cyano group, hydroxyl Base, halogen and C3-C6Cycloalkyl, wherein the C3-C6The substituent that cycloalkyl can be selected from the group is monosubstituted or polysubstituted, The group is by halogen and C1-C3Alkyl forms；Or a substituent that can be selected from the group is monosubstituted or polysubstituted phenyl base Group, the group is by C1-C6Alkyl, C1-C6Haloalkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C1-C6Alkyl alkylthio base, C1- C6Haloalkyl sulfanyl, C1-C6Alkyl sulphinyl, C1-C6Alkylsulfinyl, C1-C6Alkyl sulphonyl, C1-C6Halogen Substituted alkyl sulfonyl, C2-C6Alkyl-carbonyl, C2-C6Halogenated alkyl carbonyl, C2-C6Alkoxy carbonyl, C2-C6Halogenated alkoxy carbonyl Base, C1-C6Alkyl amino, C1-C6Haloalkylamino, C2-C8Dialkyl amido, C2-C8Halo dialkyl amido, halogen, cyanogen Base and nitro composition), in a kind of atent solvent (such as THF, DMF, dioxanes, octane, toluene and dimethylbenzene), A kind of a kind of palladium chtalyst in atent solvent (such as toluene and dimethylbenzene and DMF, or these a kind of mixture etc.) In the presence of agent (such as tetrakis triphenylphosphine palladium (0) or double (triphenylphosphine) palladium bichlorides (II)), between 25 DEG C -120 DEG C Reacted at temperature (preferably 50 DEG C -90 DEG C).Then, by a kind of product X LIX of acquisition mineral acid (such as aqueous salts Acid) handled in the presence of a kind of organic cosolvent (such as methanol, acetone, ethanol, THF etc.), changed with providing to have Formula 1y product (wherein substituent R1、R2、G1、G2、L1、R3、R4、V1、V0And R39It is as the aforementioned).These processes are many institutes Known, and previously in for example small China fir (Kosugi), positive moral (Masanori) et al., Japanese Chemical Society's publication (Bull.Chem.Soc.Japan), 60 (2), 767-8, described in 1987.
Similar chemical process can be used to R4、R5、R20、R22、R23、R24、R25、R26、R27、R28、R29And R30Middle introducing Such a substituent.
In many cases, the known compound with Formulae II is commercially available or can be by similar to text in document It is prepared by the method described in offering.Such as 3- ethylsulfonyls -5- (trifluoromethyl) pyridine-2-carboxylic acids (WO 2013180194), 3- Ethylsulfonyl pyridine-2-carboxylic acids (WO 2013180194), 3- ethylsulfonyl pyrazine -2- carboxylic acids (WO 2013180194), 3- ethylsulfonyls thiophene-2-carboxylic acid (synthesizing (Synthesis), 2007, (12), 1827-1832), 3- ethylsulfonyls -5- (trifluoromethyl) thiophene-2-carboxylic acid (WO 2013180193), 2- chloro- 6- (trifluoromethyl) pyridine-3-carboxylic acids (WO 2013180194), 5- Ethylsulfanyls thiazole -4-carboxylic acid (WO 2013180193), 2- Ethylsulfanyl thiophene -3- carboxylic acids (WO 2013180193) and the bromo- 2- methyl isophthalic acids of 4-, 1- dioxo -2,3- dihydrobenzo thiophene -7- carboxylic acids (WO 199909023),
In other cases, the synthesis for the compound with Formulae II has been developed particularly to prepare with change The compound of Formulas I is learned, and is shown in following scheme：
Scheme 6.
Scheme 7.
Scheme 8
Scheme 9
Scheme 10
Scheme 11：
Scheme 12
Compound with formula iii, IV and V known in document is commercially available or can be by similar to document In these method prepare.Such as N-2- methyl -5- (trifluoromethyl) pyridine -2,3- diamines (WO 2012086848), 6- (trifluoromethyl) pyridine -3,4- diamines (WO 2013/048214), N-3- methyl -6- (trifluoromethyl) pyridine -2,3- diamines (WO 2012/086848), N-5- methyl -2- (trifluoromethyl) pyrimidine -4,5- diamines (CAS [1023817-05-1]), N-1- methyl - 4- (trifluoromethyl) benzene -1,2- diamines (WO 2005065680), 3- amino -5- (trifluoromethyl) pyridine -2- alcohol (WO 2011049222), (the 1H)-pyrithiones (WO 2011/043404) of 3- amino -5- (trifluoromethyl) -2.
In other cases, the synthesis for the compound with formula iii, IV and V has been developed particularly to make Standby have the compound of Formula I, and is shown in following scheme：
Scheme 13
Scheme 14
Scheme 15：
Scheme 16：
Other synthesis to the compound with Formula I are shown in following scheme：
Scheme 17.
Scheme 18：
In the presence of the compound with chemical formula (I) be largely adapted to, known, for preparing every other functionalization (according to A1-A6And B1-B11Definition) standard method, such as alkanisation, halogenation, acylation, amidatioon, oximate, oxidation and reduction, The characteristic (reactivity) for the substituent that the selection of suitable preparation method is depended in these intermediate products.
These reactants can be reacted in the presence of a kind of alkali.The example of suitable alkali is alkali metal or alkaline-earth metal Hydroxide, alkali metal or alkaline earth metal hydride, alkali metal or alkaline earth metal amide, alkali metal or alkaline-earth metal alcoholates, Alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonate, alkali metal or alkaline-earth metal dialkyl amide or alkali Metal or alkaline-earth metal alkylsilylamides, alkylamine, Alkylenediamine, the saturation of free or N- alkylations or insatiable hunger Cycloalkyl amine, basic heterocycles, ammonium hydroxide and the carbocyclic ring amine of sum.It can be mentioned that example be sodium hydroxide, hydrogenation Sodium, Sodamide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, hydrofining, diisopropylamino lithium, Double (trimethylsilyl) acid amides potassium, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N- hexamethylenes Base-N, TMSDMA N dimethylamine, N, N- diethylanilines, pyridine, 4- (N, N- dimethylamino) pyridine, quinuclidine, N-methylmorpholine, benzyl three Ammonium methyl hydroxide and the -7- alkene (DBU) of 1,8- diazabicylos [5.4.0] 11.
These reagents can be reacted each other as it is, i.e.,：Without adding solvent or diluent.However, most of In the case of, it is favourable to add a kind of atent solvent or diluent or these mixture.If the reaction is deposited a kind of alkali In lower progress, then these alkali being excessively used (such as triethylamine, pyridine, N-methylmorpholine or N, N- diethylaniline) can also fill When solvent (or diluent).
The reaction advantageously from about -80 DEG C to about+140 DEG C, is preferably from about -30 DEG C to about+100 DEG C, in many feelings Carried out under condition at a temperature of between environment temperature with about+80 DEG C.
A kind of compound with Formula I can be converted into another kind with Formula I in a kind of method known per se Compound, this is by a usual manner using one or more substituents of the compound with Formula I of the starting Realized according to the replacements of another or the other one or more substituents of the present invention.
Reaction condition and parent material depending on selected suitable each situation, it is possible to for example, in a reaction Only a substituent is substituted with another substituent according to the present invention in step, or can be with same reactions steps Multiple substituents are substituted with multiple other substituents according to the present invention.
The salt of these compounds with Formula I can be prepared in a way known.Thus, for example, have The acid-addition salts of the compound of Formula I are handled by using a kind of suitable sour or a kind of suitable ion exchange reagent Come what is obtained, and with the salt of alkali be by using a kind of suitable alkali or with a kind of suitable ion exchange reagent handled come Obtain.
The salt of compound with Formula I can be converted into a usual manner free compound I, acid-addition salts (such as Handled by using a kind of suitable alkali compounds or with a kind of suitable ion exchange reagent) and alkali salt (such as it is logical Cross with a kind of suitable acid or handled with a kind of suitable ion exchange reagent).
The salt of compound with Formula I can be converted into the chemical combination with Formula I with a kind of per se known manner Other salt, the acid-addition salts of thing, such as it is transformed into other acid-addition salts, such as by using one kind in a kind of suitable solvent A kind of suitable metal salt (such as sodium, barium or silver salt, such as with silver acetate) of acid handles a kind of salt of inorganic acid (such as salt Hydrochlorate), in the solvent, a kind of inorganic salts (such as silver chlorate) formed are insoluble and therefore from the reactant mixtures In be settled out.
, can be with free with these compounds with Formula I into salt characteristic depending on the program or reaction condition Form or the form of salt obtain.
Compound with Formula I and it is appropriate when its dynamic isomer (in free form or in salt in each situation Form) can be in the form of one of possible isomers or in the form of a kind of mixture of these isomers, such as with pure different Structure body (such as enantiomer and/or diastereoisomer) form or with isomer mixture (such as enantiomeric mixture, example Such as racemic modification；Non-enantiomer mixture or raceme mixture) form presence, depending on not right present in molecule Claim number, absolute and relative configuration and/or the configuration depending on non-aromatic double bond present in molecule of carbon atom；The present invention It is related to pure isomer and possible all isomer mixtures, and in each situation of context, or even do not having Body is referred in each situation of stereochemical details, should all be understood from this layer of meaning.
The non-enantiomer mixture or racemic of the compound with Formula I in free form or salt form The mixture (obtaining for they can depend on selected parent material and program) of body can be in the physico of these components On the basis of learning difference, for example, be separated into a kind of known method by fractional crystallization, distillation and/or chromatography it is pure non-right Reflect isomers or racemic modification.
Known formula can be passed through with the enantiomeric mixture (such as racemic modification) that a kind of similar fashion obtains Method splits into optical antipode, such as by being recrystallized from a kind of optical activity solvent；Pass through the chromatography on chiral sorbent Method, such as the high performance liquid chromatography (HPLC) (HPLC) on acetylcellulose；It is solid by using specificity by means of suitable microorganism Determine enzymatic lysis；It is complexed by forming inclusion compound, such as using chiral crown ether, only one of which enantiomter；It is or logical Cross and change into diastereo-isomerism salt, for example, by make a kind of alkaline final product racemic modification and a kind of optically active acid (such as Carboxylic acid, such as camphor, tartaric acid or malic acid or sulfonic acid, such as camphorsulfonic acid) reaction, and separate and can obtain in this way Non-enantiomer mixture, such as based on its different solubilities by fractional crystallization, so as to obtain diastereoisomer, from These diastereoisomers can become desired enantiomter by the effect of suitable reagent (such as alkaline reagent) Into free.
Pure diastereoisomer or enantiomerism physical efficiency obtains according to the present invention, is not only suitable different by separating Structure body mixture, the method by generally known diastereoselectivity or enantioselective synthesis is can also be, such as By carrying out this method using a kind of suitable stereochemical parent material according to the present invention.
Can be by by the compound with Formula I and a kind of suitable oxidant (such as H2O2/ urea adduct) Reaction is carried out in the presence of acid anhydrides (for example, TFAA) and prepares N- oxides.Such oxidation is from document, for example, from medicine Learn known in magazine (J.Med.Chem.) 1989,32,2561 or WO 2000/15615.
If these single components have different bioactivity, it is advantageous that separating or synthesize in each case should Biologically more effective isomers, such as enantiomter or diastereoisomer, or isomer mixture, such as mapping Isomer mixture or non-enantiomer mixture.
These have Formula I compound and it is appropriate when its dynamic isomer (in each case in free shape Formula or salt form) it can also be obtained if appropriate in the form of hydrate and/or including other solvents, such as can be used for Those of the crystallization of existing compound in solid form.
The compound with Formula I according to the present invention is to have prevention and/or treatment in harmful organism control field The active component of value, even under low amount of application, they there is very favorable biocidal spectrum and be warm blooded species, Fish and plant are well tolerable.The dynamic of normal sensitivity and also anti-medicine is acted on according to these active components of the present invention All or individual other stages of development of thing harmful organism (representative of such as insect or Acarina).According to the active component of the present invention Kill insect or acaricidal activity and can directly display in itself, that is, either immediately or only after some times in past (such as During husking) occur to destroy harmful organism；Or display indirectly, such as spawning and/or incubation rate are reduced, corresponding at least 50% Destructive rate (death rate) excellent activity.
Compound with Formula I can be used for resisting and controlling insect pest (such as Lepidoptera, dipteron Mesh, Semiptera, Thysanoptera, Orthoptera, Dictyoptera, coleoptera, Siphonaptera, Hymenoptera and Isoptera) and other moved without vertebra Harmful organism (for example, mite, nematode and the mollusk pests) of thing infect.Insects, mite class, Nemata and software Animal class is collectively referenced hereinafter as harmful organism.These harmful organisms that can be resisted and control by using the compounds of this invention Including those with agricultural (term includes the cultivations of the crops of food and fiber product), gardening and herding, pet, forestry and The product in vegetables source (such as fruit, grain and timber) stores relevant harmful organism；Those infringements with man-made structures and The relevant harmful organism of the transmissions of humans and animals；And public hazards harmful organism (such as fly).
The example for the pest that can be controlled by the compound with Formula I includes：Black peach aphid (aphid), cotton Aphid (aphid), black bean aphid (aphid), Lygus Hahn (fleahopper), red cotton bug category (fleahopper), brown plant-hopper (plant hopper), rice green leafhopper (leafhopper), Bemisia spp (smelly stinkbug), America stinkbug category (smelly stinkbug), Leptocorisa spp category (smelly stinkbug), Frankliniella occidentalis (thrips), Thrips (Ji Horse), colorado potato bug (colorado potato bug), Mexico's Anthonomusgrandis (anthonomus grandis), kidney Aspidiotus category (scale insect), Aleyrodes (aleyrodid), Bemisia tabaci (aleyrodid), European corn borer (European corn borer), extra large spodoptera (cotton leafworm), tobacco budworm (cigarette night Moth), bollworm (bollworm), paddy reality noctuid (bollworm), cotton leafroller (cotton leaf roller), large white butterfly (white butterfly), pickles Moth (Plutella xylostella) (diamondback moth (Diamond back moth)), Agrotis (cutworm), striped rice borer (two Change snout moth's larva), African migratory locust (locust), Australian pestilence locust (locust), Diabroticaspp (rootworm), panonychus ulmi (apple Red spider), Jie-Li enzyme-SQ (citrus red mite), T.urticae Koch (Tetranychus urticae), Tetranychus cinnabarinus (red spider), tangerine rue rust mite (mandarin orange Citrus rust mite), Polyphagotarsonemus latus Banks (the thin mite of tea), short whisker Acarapis (grape brevipalpus), boophilus microplus (Boophilus annulatus), Dermacentor variabilis (american dog tick), ctenocephalides felis (cat flea), Liriomyza (leaf miner), housefly (housefly), Aedes aegypti (mosquito), Anopheles (mosquito), Culex (mosquito), Lucilia (calliphorid), Groton bug (cockroach), American cockroach (cockroach), the rough Lian in east (cockroach), Australia The termite (such as Australia's Cryptotermes) of Termitidae, Kalotermitidae (such as new Cryptotermes), Rhinotermitidae (such as coptotermes formosanus of taiwan, Huang Limb reticulitermes flavipe, eastern subterranean termite, Reticulitermes virginicus, west reticulitermes flavipe and Sang Te reticulitermes flavipes) and Termitidae (such as yellow ball termite (Globitermes sulphureus)), Solenopsis geminata (fiery ant), monomorium pharaonis (little red ant), Damalinia and Linognathus (sting lice With suck lice), Meloidogyne (root-knot nematode), ball Heterodera and Heterodera (SCN), Pratylenchus (rotten nematode), Rhodophyllus (radopholus similes thorne), pulvinulus sword Turbatrix (citrus nematode), haemonchus contortus (twisted stomach Worm), Caenorhabditis elegans (vinegar worm vinegar eel), Trichostrongylus (gastrointestinal nematode) and reticulate pattern Agriolimax agrestis Linnaeus (slug).
More examples of above-mentioned harmful organism are：
From Acarina, such as lower hair Eriophyes (Acalitus spp.), acupuncture Eriophyes (Aculus spp), narrow goitre Mite category (Acaricalus spp.), Genus Aceria (Aceria spp.), Acarus siro (Acarus siro), Amblyomma (Amblyomma spp.), Argas (Argas spp.), Boophilus (Boophilus spp.), short whisker Acarapis (Brevipalpus spp.), Bryobia (Bryobia spp), upper three section Eriophyes (Calipitrimerus spp.), skin mite Belong to (Chorioptes spp.), Dermanyssus gallinae (Dermanyssus gallinae), Dermatophagoides (Dermatophagoides Spp), Eotetranychus (Eotetranychus spp), Eriophyes (Eriophyes spp.), half Tarsonemus (Hemitarsonemus spp), Hyalomma (Hyalomma spp.), Isodesspp (Ixodes spp.), Oligonychus (Olygonychus spp), Ornithodoros (Ornithodoros spp.), Polyphagotarsonemus latus Banks (Polyphagotarsone Latus), Panonychus citri category (Panonychus spp.), tangerine rue rust mite (Phyllocoptruta oleivora), herbivore mite (Phytonemus spp.), Tarsonemus (Polyphagotarsonemus spp), Psoroptes (Psoroptes spp.), fan Carrapato category (Rhipicephalus spp.), Rhizoglyphus (Rhizoglyphus spp.), Sarcoptesspp (Sarcoptes Spp.), Steneotarsonemus (Steneotarsonemus spp), instep line category (Tarsonemus spp.) and Tetranychus (Tetranychus spp.)；
From Anoplura, such as Haematopinus (Haematopinus spp.), Linognathus (Linognathus spp.), people Pediculus (Pediculus spp.), Pemphigus (Pemphigus spp.) and Psylla spp (Phylloxera spp.)；
From coleoptera, such as lack grand click beetle category (Agriotes spp.), European chafer (Amphimallon majalis) (Amphimallon Majale), east different beetle (Anomala orientalis), flower are as category (Anthonomus spp.), Aphodius It is hidden that (Aphodius spp), corn intend leather winged beetle (Astylus atromaculatus), cockchafer category (Ataenius spp), beet Eat first (Atomaria linearis), beet shin flea beetle (Chaetocnema tibialis), Galeruca (Cerotoma Spp), single leaf click beetle category (Conoderus spp), root neck are as category (Cosmopolites spp.), green gold tortoise (Cotinisnitida), Curculio (Curculio spp.), round end rhinoceros cockchafer category (Cyclocephala spp), round end rhinoceros gold Chinemys (Dermestes spp.), Diabroticaspp (Diabrotica spp.), Argentinian pocket worm (Diloboderus Abderus), epilachna genus (Epilachna spp.), Eremnus spp., black different pawl sugarcane cockchafer (Heteronychus Arator), coffee berryborer (Hypothenemus hampei), Lagria vilosa, colorado potato bug (Leptinotarsa DecemLineata), Lissorhoptrusoryzophilus category (Lissorhoptrus spp.), Liogenys spp, Maecolaspis spp, maroon Suede cockchafer (Maladera castanea), Megascelis spp, Melighetes aeneus, cockchafer category (Melolontha Spp.), Myochrous armatus, saw-toothed grain beetle category (Orycaephilus spp.), ear beak are as belonging to (Otiorhynchus Spp.), Phyllophaga (Phyllophaga spp), spot are as category (Phlyctinus spp.), rutelian category (Popillia Spp.), rape phyllotreta (Psylliodes spp.), Rhyssomatus aubtilis, Rhizopertha (Rhizopertha Spp.), Scarabaeidae (Scarabeidae), Sitophilus (Sitophilus spp.), gelechiid category (Sitotroga spp.), puppet Cutworm category (Somaticus spp), sharp Rhynchophorus (Sphenophorus spp), soybean stem are as (Sternechus Subsignatus), Tenebrio (Tenebrio spp.), Tribolium (Tribolium spp.) and spot khapra beetle category (Trogoderma spp.)；
From Diptera, such as Aedes (Aedes spp.), Anopheles (Anopheles spp), jowar awns fly (Antherigona soccata.), olive fruit trypetid (Bactrocea oleae), garden march fly (Bibio Hortulanus), Bradysia Sciara (Bradysia spp.), calliphora erythrocephala (Calliphora erythrocephala), small Bar Anastrepha (Ceratitis spp.), Carysomyia (Chrysomyia spp.), Culex (Culex spp.), Cuterebra (Cuterebra spp.), few hair on the neck Anastrepha (Dacus spp.), Delia (Delia spp), Drosophila melanogaster (Drosophilamelanogaster), Fannia (Fannia spp.), Gasterophilus (Gastrophilus spp.), Geomyza tripunctata, Glossina (Glossina spp.), Hypoderma (Hypoderma spp.), Hippobosca (Hyppobosca spp.), Liriomyza (Liriomyza spp.), Lucilia (Lucilia spp.), Hippelates (Melanagromyza spp.), Musca (Musca spp.), Oestrus (Oestrus spp.), cecidomyiia category (Orseolia Spp.), Oscinella frit (Oscinella frit), lamb's-quarters spring fly (Pegomyia hyoscyami), Phorbia (Phorbia Spp.), around Anastrepha (Rhagoletis spp), Rivelia quadrifasciata, Scatella spp, Sciara (Sciara spp.), Stomoxys (Stomoxys spp.), Gadfly (Tabanus spp.), tapeworm category (Tannia spp.) with And big uranotaenia (Tipula spp.)；
From Semiptera, for example, knurl coried (Acanthocoris scabrator), Bemisia spp, alfalfa plant bug, Amblypeltanitida, sea shrimp shield coried (Bathycoelia thalassina), native chinch bug category, Cimex, Clavigralla tomentosicollis, fleahopper category (Creontiades spp.), Distantiella theobroma, Dichelops Furcatus, red cotton bug category, Edessa spp, America stinkbug category (Euchistus spp.), six spot cabbage bug (Eurydema Pulchrum), Eurygasterspp category, eating attraction, the recessed huge section chief stinkbug (Horcias nobilellus) of tool, Leptocorisa spp category It is (Leptocorisa spp.), Lygus Hahn, the large a red-spotted lizard category in the torrid zone, harlequin bug (Murgantia histrionic), new Long coried category (Neomegalotomus spp), cigarette fleahopper (Nesidiocoris tenuis), Bemisia spp, plan chinch bug (Nysius Simulans), island stinkbug (Oebalus insularis), skin stinkbug category, wall stinkbug category, Rhodnius, cocoa mirid pentatomid, chestnut soil Stinkbug (Scaptocoris castanea), black stinkbug category (Scotinophara spp.), Thyanta spp, cone nose Eimeria, cassava Lace bug (Vatiga illudens)；Without net long tube Aphis, Adalges spp, Agalliana ensigera, tal fibre Ji Aoni Wood louse (Agonoscena targionii), Aleyrodes (Aleurodicus spp.), thorn Aleyrodes (Aleurocanthus Spp), sugarcane cave aleyrodid, fur aleyrodid (Aleurothrixus floccosus), wild cabbage aleyrodid (Aleyrodes Brassicae), chlorita biguttula (Amarasca biguttula), the prominent leafhopper (Amritodus atkinson) of mango length, kidney targe A red-spotted lizard category, Aphidiadae, Aphis, a red-spotted lizard category (Aspidiotus spp.), eggplant ditch are without net aphid, potato wood louse (Bactericera Cockerelli), small Aleyrodes, short-tail Aphis (Brachycaudus spp), brevicoryne brassicae, noise made in coughing or vomiting Psylla spp, double tail aphids (Cavariella aegopodii Scop.), lecanium category, brown round a red-spotted lizard, net seed blade of grass circle a red-spotted lizard, cicadellid category (Cicadella Spp), great Bai leafhopper (Cofana spectra), hidden tumor aphid genus, leafhopper category (Cicadulina spp), Coccushesperidum, maize wing Leafhopper, naked Aleyrodes, diaphorina citri, Diuraphis noxia, western rounded tail Aphis, Empoasca flavescens, eriosoma lanigerum, grape leafhopper category, Wax clam category, eucalyptus camaldulensis wood louse (Glycaspis brimblecombei), turnip aphid, big tail Aphis (Hyalopterus spp), Super knurl aphid kind, mango greenery cicada (Idioscopus clypealis), African leafhopper (Jacobiasca lybica), small brown rice planthopper Category, ball heavily fortified point a red-spotted lizard, lepidosaphes shimer, radish aphid (Lopaphis erysimi), Lyogenys maidis, long tube Aphis, froghopper category (Mahanarva spp), Flatidae (Metcalfa pruinosa), wheat are without net aphid, Myndus crudus, tumor aphid genus, platform Gulf fragrant-flowered garlic aphid, rice green leafhopper category, brown paddy plant hopper category (Nilaparvata spp.), the big greenbug of pears, Bermuda grass trifle shell worm (Odonaspis ruthae), parasitic sugar cane cottony aphid, red bayberry edge aleyrodid, Kao Shi wood louses, Parlatoria, Pemphigus, corn wax Cicada, flat angle plant hopper category, phorodon aphid, Phylloxera spp, Planococcus, white armored scale category, mealybug category, cotton plant bug (Pseudatomoscelis seriatus), Psylla spp, cotton a red-spotted lizard (Pulvinaria aethiopica), large bamboo hat with a conical crown and broad brim Aspidiotus category, Quesada gigas, recilia dorsalis (Recilia dorsalis), Rhopalosiphum, black bourch category, Scaphoideus, y-bend Aphis, Wheat aphid category (Sitobion spp.), white backed planthopper, triangle clover springtail (Spissistilus festinus), streak plant hopper (Tarophagus Proserpina), sound Aphis, Aleyrodes, Tridiscus sporoboli, certain herbaceous plants with big flowers mealybug category (Trionymus Spp.), African wood louse, tangerine arrowhead scales, flame Erythroneura spp (Zygina flammigera), Zyginidia scutellaris；
From Semiptera, such as Cimex, the blind honeybee of cocoa knurl, red cotton bug category, America stinkbug category, Eurygasterspp category, Leptocorisa spp category (Leptocorisa spp.), Bemisia spp, intend lace bug category, be Rhodnius, Sahlbergella singularis (Scotinophara spp.), black Stinkbug category and Triatoma；
From Homoptera, such as fur aleyrodid, vegetable powder lice, kidney Aspidiotus category, Aphidiadae, Aphis, thin targe shell Eimeria (Aspidiotus spp.), Bemisia tabaci, lecanium category, dark brown Aspidiotus, Chrysomphalus ficus, Coccushesperidum, Empoasca spp category, apple cotton Aphid, Erythroneura spp category, wax clam category, small brown rice planthopper category, water and soil heavily fortified point a red-spotted lizard, Lepidosaphes, long tube Aphis, tumor aphid genus, rice green leafhopper category, it is brown fly Pediculus, Parlatoria, Pemphigus, Planococcus (Planococcus spp.), intend white wheel shield shell Eimeria, mealybug category, It is Psylla spp, cotton a red-spotted lizard, tooth armored scale category, Rhopalosiphum, pearl lecanium category, Scaphoideus, y-bend Aphis, wheat aphid category, Trialeurodes vaporariorum Westwood, non- Continent wood louse and citrus point shield rank；
From Hymenoptera, such as top Myrmecina (Acromyrmex), three section tenthredinidaes (Arge spp.), Bu Qieyebai Ant category (Atta spp.), stem tenthredinidae (Cephus spp.), Diprion (Diprion spp.), Diprionidae (Diprionidae), pine sawfoy (Gilpinia polytoma), pear fruit sawfly category (Hoplocampa spp.), hair ant category (Lasius spp.), monomorium pharaonis (Monomorium pharaonis), Neodiprion (Neodiprion spp.), agriculture ant Belong to (Pogonomyrmex spp), red fire ant (Slenopsis invicta), Solenopsis (Solenopsis spp.) and Hu Honeybee category (Vespa spp.)；
From Isoptera, for example, formosanes category (Coptotermes spp), termite (Corniternes cumulans), Principal columns of a hall Cryptotermes (Incisitermes spp), Macrotermes (Macrotermes spp), Australia Cryptotermes (Mastotermes Spp), small Cryptotermes (Microtermes spp), Reticulitermes (Reticulitermes spp.)；Solenopsis geminata (Solenopsis geminate)；
From Lepidoptera, for example, Acleris spp category (Acleris spp.), Adoxophyessp (Adoxophyes spp.), Clearwing moth category (Aegeria spp.), Noctua (Agrotis spp.), cotton leafworm (Alabama argillaceae), form sediment Mealworm category (Amylois spp.), Anticarsia (Anticarsia gemmatalis), Archips spp (Archips spp.), Silver-colored moth category (Argyresthia spp.), Argyrotaenia spp category (Argyrotaenia spp.), gamma category (Autographa Spp.), cotton lyonetid (Bucculatrix thurberiella), corn pattern noctuid (Busseola fusca), amyloid plaque snout moth (Cadra cautella), peach fruit moth (Carposina nipponensis), straw borer spp (Chilo spp.), leaf roller Belong to (Choristoneura spp.), more climing tangerine crambid (Chrysoteuchia topiaria), grape codling moth (Clysia ambiguella) (Clysia Ambiguella), leaf roll snout moth's larva category (Cnaphalocrocis spp.), cloud volume moth category (Cnephasia spp.), line volume moth category (Cochylis spp.), casebearer moth (Coleophora spp.), hedge bean powder butterfly (Colias lesbia), Cosmophila Flava, Crambus Fabricius (Crambus spp), big Oeobia undalis (Crocidolomia binotalis), Cryptophlebia leucotreta (Cryptophlebia leucotreta), boxwood moth (Cydalima perspectalis), moth-eaten moth category (Cydia Spp.), Diaphania perspectalis (Diaphania perspectalis), bar Crambus Fabricius (Diatraea spp.), the Sudan bollworm (Diparopsis castanea), Earias (Earias spp.), dehydrated sweet potato snout moth's larva (Eldana saccharina), amyloid plaque Snout moth's larva category (Ephestia spp.), leaf steinernema category (Epinotia spp), salt pool moths attracted by lamplight (Estigmene acrea), bean-pod borer (Etiella zinckinella), flower steinernema category (Eucosma spp.), ring pin list line moth (Eupoecilia Ambiguella), Euproctis (Euproctis spp.), cut Noctua (Euxoa spp.), Feltia jaculiferia, Grapholita (Gra-pholita spp.), malachite worm moth (Hedya nubiferana), Heliothis (Heliothis Spp.), Oeobia undalis (Hellula undalis), wild snout moth's larva category (Herpetogramma spp), fall webworms (Hyphantria Cunea), tomato pinworm moth (Keiferia lycopersicella), Corn snout moth's larva (Lasmopalpus lignosellus), rotation Line leaf miner (Leucoptera scitella), the thin moth category of leaf mining (Lithocollethis spp.), grape flower wing steinernema (Lobesia botrana), Loxostege bifidalis, Euproctis (Lymantria spp.), Lyonetiaspp (Lyonetia Spp.), curtain Lasiocampa (Malacosoma spp.), lopper worm (Mamestra brassicae), maduca sexta (Manduca sexta), secret Noctua (Mythimna spp), Noctua (Noctua spp), autumn geometrid moth category (Operophtera spp.), Orniodes indica, corn borer, super steinernema category (Pammene spp.), brown epiblema (Pandemis spp.), small noctuid (Panolis flammea), common moth stem noctuid (Papaipema nebris), red bell Gelechiid (Pectinophora gossypiela), coffee leafminer (Perileucoptera coffeella), America mythimna separata (Pseudaletia unipuncta), potato tuberworm (Phthorimaea operculella), pieris rapae (Pieris Rapae), vegetable powder moth category (Pieris spp.), diamondback moth (Plutella xylostella), little Bai Yponomeutas (Prays Spp.), fragrant (Richia in chi Noctua (Pseudoplusia spp), peppermint ash noctuid (Rachiplusia nu), west beans ground Albicosta), white standing grain snout moth's larva category (Scirpophaga spp.), moth stem Noctua (Sesamia spp.), long hair volume moth category (Sparganothis spp.), Spodoptera (Spodoptera spp.), cotton leafroller (Sylepta derogate), Synanthedon (Synanthedon spp.), different boat pretty young woman belong to (Thaumetopoea spp.), leaf roller category (Tortrix Spp.), cabbage looper (Trichoplusia ni), tomato gelechiid (Tuta absoluta) and Yponomeuta (Yponomeuta spp.)；
From Mallophaga, for example,
Damalinia and Trichodectes；
From Orthoptera, such as Lian category, Blatella, Gryllotalpa spp, leucophaea maderae, migratory locusts category, northern mole cricket (Neocurtilla hexadactyla), Periplaneta, mole cricket spp (Scapteriscus spp) and desert locust category；
Category (Liposcelis spp.) is nibbled from Corrodentia, such as lice；
From Siphonaptera, such as Ceratophyllus (Ceratophyllus spp.), Ct (Ctenocephalides ) and Xanthopsyllacheopis (Xenopsylla cheopis) spp.；
From Thysanoptera, for example,
Calliothrips phaseoli, flower thrips category (Frankliniella spp.), Heliothrips (Heliothrips spp), brown Taeniothrips (Hercinothrips spp.), single parent's Thrips (Parthenothrips Spp.), the hard thrips of aurantiin (Scirtothrips aurantii), soybean thrips (Sericothrips variabilis), Taeniothrips (Taeniothrips spp.), Thrips (Thrips spp)；And
From Thysanoptera, such as silverfish (Lepisma saccharina).
According to the present invention active component can be used for control, namely contain or destroy the above-mentioned type harmful organism, this A little harmful organisms are occurred especially on plant, useful plant especially in agricultural, in gardening and in forestry and On ornamental plant, or on the organ of these plants, such as fruit, flower, leaf, stem, stem tuber or root, and in certain situation Under, or even the plant organ formed subsequent time point still keeps protected these harmful organisms of resistance.
Suitable target crop is specifically cereal, such as wheat, barley, rye, oat, rice, corn or sorghum；Sweet tea Dish, such as sugar beet or fodder beet；Fruit, such as apple class fruit, stone fruit or pitted fruit, such as apple, Pears, plum, peach, almond, cherry or berry, such as strawberry, raspberry or blackberry, blueberry；Legume, such as broad bean, lens, pea Beans or soybean；Oil crops, such as rape, leaf mustard, opium poppy, olive, sunflower, coconut, castor-oil plant, cocoa or peanut；Cucurbit, Such as pumpkin, cucumber or muskmelon；Fibre plant, such as cotton, flax, hemp or jute；Cedra fruits, such as orange, lemon Lemon, grape fruit or orange；Vegetables, such as spinach, lettuce, asparagus, wild cabbage, carrot, onion, tomato, potato or bell pepper； Canella, such as avocado, Chinese cassia tree or camphor；And also tobacco, nut, coffee, eggplant, sugarcane, tealeaves, pepper, grape Tree, hop, Plantaginaceae, lactiferous plant and ornamental plant.
In another aspect, the present invention may also refer to control by phytotrophy nematode (it is entozoic-, it is half entozoic- And ectoparasite nematode) cause a kind of method of infringement to plant or part thereof, the nematode of especially following phytotrophy, such as Root-knot nematode (root knot nematodes), M hapla (Meloidogyne hapla), Meloidogyne incognita (Meloidogyne incognita), javanese root knot nematode (Meloidogyne javanica), peanut root-knot nematode (Meloidogyne arenaria) and other Meloidogyne species (Meloidogyne species)；Sporangiocyst forms line Worm (cyst-forming nematodes), globodera rostochiensis (Globodera rostochiensis) and other ball spores Capsule Turbatrix species (Globodera species)；Cereal cyst nematode (Heterodera avenae), soybean cyst nematode Heterodera glycines (Heterodera glycines), beet SCN (Heterodera schachtii), red clover golden nematode (Heterodera trifolii) and other Heterodera species (Heterodera species)；Kind goitre nematode (Seed gall nematodes), grain Turbatrix species (Anguina species)；Stem and blade face nematode (Stem and Foliar nematodes), Aphelenchoides species (Aphelenchoides species)；Seta nematode (Sting Nematodes), long anal spine nematode (Belonolaimus longicaudatus) and other thorn Turbatrix species；Pine tree line Worm (Pine nematodes), pine wood nematode (Bursaphelenchus xylophilus) and other Bursaphelenchus species (Bursaphelenchus species)；Annular nematode (Ring nematodes), loop wire Eimeria species (Criconema Species), small loop wire Eimeria species (Criconemella species), Criconemoides species (Criconemoides Species), middle ring Turbatrix species (Mesocriconema species)；Stem and lepisphere Ditylenchus dipsaci (Stem and bulb Nematodes), rot stem nematodes (Ditylenchus destructor), Ditylenchus dip saci (Ditylenchus ) and other Ditylenchus species (Ditylenchus species) dipsaci；Bore nematode (Awl nematodes), cone line Eimeria species (Dolichodorus species)；Helicotylenchus (Spiral nematodes), multi-head spiral nematode (Heliocotylenchus multicinctus) and other helix Eimeria species (Helicotylenchus species)；Sheath and sheath shape nematode (Sheath and sheathoid nematodes), sheath Turbatrix species (Hemicycliophora species) and half Criconemoides species (Hemicriconemoides species)；Latent root line Eimeria species (Hirshmanniella species)；Branch nematode (Lance nematodes), Stephanurus species (Hoploaimus species)；False root-knot nematode (false rootknot nematodes), pearl Turbatrix species (Nacobbus species)；Needle-like nematode (Needle nematodes), cross band minute hand nematode (Longidorus ) and other minute hand Turbatrix species (Longidorus species) elongatus；Pin nematode (Pin Nematodes), Pratylenchus species (Pratylenchus species)；Rotten nematode (Lesion nematodes), piebald Pratylenchidae (Pratylenchus neglectus), Cobb root (Pratylenchus penetrans), bending are short Body nematode (Pratylenchus curvitatus), Gooch Pratylenchidae (Pratylenchus goodeyi) and other are short Body Turbatrix species (Pratylenchus species)；Citrus similes thorne (Burrowing nematodes), radopholus Nematode (Radopholus similis) and other radopholus category species (Radopholus species)；Kidney shape nematode Spiral nematode (Rotylenchus robustus), kidney shape of (Reniform nematodes), sieve Bai Shi is spiraled nematode (Rotylenchus reniformis) and other Turbatrix species of spiraling (Rotylenchus species)；Shield Turbatrix Species (Scutellonema species)；Short and thick nematode (Stubby root nematodes), original burr nematode (Trichodorus primitivus) and other burr Turbatrix species (Trichodorus species), intend burr line Eimeria species (Paratrichodorus species)；Species of Tylenchorhynchus Nematodes (Stunt nematodes), purslane species of Tylenchorhynchus Nematodes (Tylenchorhynchus claytoni), along inverse species of Tylenchorhynchus Nematodes (Tylenchorhynchus dubius) and other dwarfings Turbatrix species (Tylenchorhynchus species)；Citrus nematode (Citrus nematodes), puncture Turbatrix kind Class (Tylenchulus species)；Dirk nematode (Dagger nematodes), Xiphinema species (Xiphinema species)；And the line insect types that other plant is parasitic, such as sub- grain Turbatrix (Subanguina spp.), Hypsoperine Category, big coronule Turbatrix (Macroposthonia spp.), Melinius category, punctum cyst category (Punctodera spp.), And five ditch Turbatrix (Quinisulcius spp.).
These compounds of the present invention, which also have, is directed to molluscan activity.These molluscan examples include, example Such as apple Cionellidae；A Yong Limaxs (Arion) (greyish black A Yong slugs (A.ater), ring spot A Yong slugs (A.circumscriptus), garden A Yong slugs (A.hortensis), reddish brown A Yong slugs (A.rufus))；Bradybaenidae (shrub bar snail (Bradybaena fruticum))；Cepaea (garden snail (C.hortensis), forest snail (C.nemoralis))；ochlodina；Grey Limax (Deroceras) (wild grey slug (D.agrestis), D.empiricorum, field ash slug (D.laeve), flower garden ash slug (D.reticulatum))；Disk spiral shell category (Discus) (D.rotundatus)；Euomphalia；Native snail category (Galba) (section shape soil snail (G.trunculata))；Small Cepaea (Helicelia) (the small snail of IITTALA (H.itala), cloth tie up small snail (H.obvia))；Helicidae Helicigona arbustorum)；Helicodiscus；Helicella (Helix) (open helix (H.aperta))；Limax (Limax) (greyish black slug (L.cinereoniger), yellow slug (L.flavus), edge slug (L.marginatus), big slug (L.maximus), soft slug (L.tenellus))；Lymnaea (Lymnaea)；Milax(M.gagates、 M.marginatus、M.sowerbyi)；Auger shell category (Opeas)；Bottle spiral shell category (Pomacea) (P.canaticulata)；Watt Lou snail Bos (Vallonia) and Zanitoides.
Term " crop " should be understood also to include having become as the result of conventional breeding methods or gene engineering method Must to herbicide (such as Bromoxynil) or classes of herbicides (such as HPPD inhibitor, ALS inhibitor, such as primisulfuronmethyl, prosulfuron with And trifloxysulfuron, EPSPS (5- enol-pyrovyl-shikimates -3- phosphoric acid-synzyme) inhibitor, (glutamine synthesizes GS Enzyme) inhibitor) there is the crop of tolerance.Become by conventional breeding methods (mutagenesis) to imidazolone such as methoxy miaow The example that careless smoking set has the crop of tolerance isSummer rape (Canola (Canola)).Due to heredity Engineering method and the example that has been assigned the crop to a variety of herbicides or the other tolerance of a variety of classes of herbicides includes glyphosate With careless fourth phosphine resistant corn kind, theyWithIt is commercially available under trade (brand) name.
Term " crop " is also understood as also including by using recombinant DNA technology convert and can having synthesized one kind Or the crop plants of multiple choices acting toxins, these toxin are for example, it is known that such as bacterium from toxin producing, especially bud Those of spore Bacillus.
Such as insecticidal protein can be included by the toxin of these Expressed in Transgenic Plant, such as from bacillus cereus Or the insecticidal protein of Japanese beetle bacillus；Or the insecticidal protein from bacillus thuringiensis, such as delta-endotoxin, Such as CryIA (b), CryIA (c), CryIF, CryIF (a2), CryIIA (b), CryIIIA, CryIIIB (b1) or Cry9c, or Trophophase insecticidal protein (VIP), such as VIP1, VIP2, VIP3 or VIP3A；Or bacterial clone nematode kills insect egg Such as luminous bacillus, Xenorhabdus nematophilus in vain, such as Photorhabdus or Xenorhabdus,；The toxin as caused by animal, example Such as scorpion toxin, spider toxin, wasp toxin and other insect-specific neurotoxins；By mycetogenetic toxin, such as chain Mycotoxin；Lectins, such as pea haemoglutinin, barley haemoglutinin or snowdrop haemoglutinin；Agglutinin；Albumen enzyme level Agent, such as trypsin inhibitor, serpin, stem tuber storage protein, cystatin, Papain enzyme level Agent；Ribosome inactivating protein (RIP), such as ricin (WA), corn-RIP, abrin, sponge gourd toxin, saporin or different strain Bryonia toxalbumin；Steroid metabolism enzyme, such as 3- hydroxy steroids oxidizing ferment, the solid acid-UDP- glycosyls-transferase of husking class, courage Sterol oxidizing ferment, moulting hormone inhibitor, HMG-COA- reductases, ion channel blocking agent, such as sodium channel or calcium channel Blocking agent, JH esterase, diuretic hormone acceptor, stilbene synthase, bibenzyl synthases, chitinase and dextranase.
In the context of the present invention, delta-endotoxin, for example, CryIA (b), CryIA (c), CryIF, CryIF (a2), CryIIA (b), CryIIIA, CryIIIB (b1) or Cry9c, or trophophase insecticidal protein (VIP), such as VIP1, VIP2, VIP3 or VIP3A should be clearly understood that to be also hybridization toxin, truncated toxins and modification toxin.Mixed type toxin is to pass through (see, e.g. WO 02/15701) caused by the Combination nova restructuring of the different zones of those albumen.Truncated toxins, such as one It is known to truncate CryIA (b).In the case of the toxin through modification, one or more amino acid of naturally occurring toxin It is replaced.Preferably will not be that naturally occurring protease recognition sequence is inserted into toxin in these amino acid replacements, example As in the case of CryIIIA055, cathepsin-D- recognition sequences are inserted into a CryIIIA toxin (referring to WO 03/018810)。
Such toxin can synthesize the example of genetically modified plants of such toxin and be disclosed in such as EP-A-0 374 753rd, in WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO 03/052073.
Method for preparing such genetically modified plants is known for one of ordinary skill in the art and retouched State in for example above-mentioned publication.CryI- types DNA and its preparation are for example from WO 95/34656, EP-A- 0 367 474, it is known in EP-A-0 401 979 and WO 90/13651.
It is included in the toxin in genetically modified plants so that plant has tolerance to harmful insect.These insects may reside in Any classification of insect group, but be especially that typically in beetle (coleoptera), dipteran (Diptera) and butterfly (Lepidoptera) It was found that.
Genetically modified plants including one or more coded insect-killing agent resistances and the gene for expressing one or more toxin Be it is known and it is some of be commercially available.The example of such plant is： (corn variety, expression CryIA (b) toxin)；YieldGard(corn variety, expressing CryIIIB (b1) toxin)；YieldGard(corn variety, expressing CryIA (b) and CryIIIB (b1) toxin)；(corn variety, express Cry9 (c) toxin)；Herculex(corn variety, express the tolerance of CryIF (a2) toxin and realization to herbicide grass fourth phosphine ammonium The enzyme phosphinothricin N acetyl transferase (PAT) of property)；NuCOTN(cotton variety, expressing CryIA (c) toxin)； Bollgard(cotton variety, expressing CryIA (c) toxin)；Bollgard(cotton variety, expression CryIA (c) and CryIIA (b) toxin)；(cotton variety, expression VIP toxin)；(Potato Cultivars, expression CryIIIA toxin)；GT Advantage (GA21 glyphosate tolerants character), CB Advantage (Bt11 corn borers (CB) character) and
Other examples of such genetically modified crops are：
1.Bt11 corns, just reach seeds company (Syngenta Seeds SAS), Huo Bitelu (Chemin de from first L ' Hobit) 27, F-31790 Sheng Suweier (St.Sauveur), France, registration number C/FR/96/05/10.The jade of genetic modification Chinese sorghum, CryIA (b) toxin truncated by transgene expression, make it to resist European corn borer (corn borer and powder stem snout moth's larva) Invasion and attack.Bt11 corns also transgenosis PAT enzymes are expressed to reach the tolerance to herbicide grass fourth phosphine ammonium salt.
2.Bt176 corns, just reach seeds company (Syngenta Seeds SAS), Huo Bitelu (Chemin de from first L ' Hobit) 27, F-31790 Sheng Suweier (St.Sauveur), France, registration number C/FR/96/05/10.The jade of genetic modification Chinese sorghum, by transgene expression CryIA (b) toxin, make it to resist the invasion and attack of European corn borer (corn borer and powder stem snout moth's larva). Bt176 corns also transgenosis PAT enzymes are expressed to reach the tolerance to herbicide grass fourth phosphine ammonium salt.
3.MIR604 corns, just reach seeds company (Syngenta Seeds SAS), Huo Bitelu (Chemin from first De l ' Hobit) 27, F-31790 Sheng Suweier (St.Sauveur), France, registration number C/FR/96/05/10.By turning CryIIIA toxin of the gene expression through modification becomes the corn of anti-insect.This toxin is by inserting a cathepsin-D- The Cry3A055 of protease recognition sequence modification.The preparation of such rotaring gene corn plant is described in WO 03/018810.
The corns of 4.MON 863, from Meng Shan all European Company (Monsanto Europe S.A.), 270-272 Te Fulun Main road (Avenue de Tervuren), B-1150 Brussels, Belgium, registration number C/DE/02/9.MON 863 is expressed CryIIIB (b1) toxin, and it is resistant to some coleopterons.
The cottons of 5.IPC 531, from Monsanto Company 270-272 Te Fulun main roads (Avenue de Tervuren), B- 1150 Brussels, Belgium, registration number C/ES/96/02.
6.1507 corns, from pioneer Worldwide, Inc (Pioneer Overseas Corporation) (Belgium, Bu Lu Sai Er, Tedesco main road (Avenue Tedesco), 7B-1160), registration number C/NL/00/10.The corn of genetic modification, table Up to protein C ry1F to realize to the resistances of some lepidopterous insects and expression PAT protein to realize to herbicide grass fourth phosphine The tolerance of ammonium salt.
The corns of 603 × MON of 7.NK 810, from Meng Shan all European Company (Monsanto Europe S.A.), 270- 272 De Tewenrui street (Avenue de Tervuren), B-1150 Brussels, Belgium, registration number C/GB/02/M3/ 03.By the way that the kind NK 603 of genetic modification and MON 810 are hybridized, it is made up of the hybrid corn variety of conventional breeding.NK The CP4EPSPS protein that the expression of the corn genes of 603 × MON 810 is obtained by Agrobacterium strains CP4, is allowed to resistance to weeding Agent(containing glyphosate), and CryIA (b) poison obtained by B. thuringiensis subspecies Element, it is allowed to resistance to some lepidopterous insects, including European corn borer.
The genetically modified crops of anti-insect plant are also described in BATS (Zentrum f ü r Biosicherheit und The Basel of Nachhaltigkeit, Zentrum BATS, Clarastrasse 13,4058, Switzerland) report in 2003.
Term " crop ", which is appreciated that, also to be included by using recombinant DNA technology and by so conversion can The crop of enough antipathogen of the synthesis with selectively acting, these antipathogens are for example so-called " pathogenesis-related proteins " (PRP, see, for example, EP-A-0 392 225).Such antipathogen and the transgenosis that such antipathogen can be synthesized The example of plant is known for example from EP-A-0 392 225, WO 95/33818 and EP-A-0 353 191.Produce such The method of genetically modified plants is commonly known for those skilled in the art and is described in for example above-mentioned disclosure In thing.
By such Expressed in Transgenic Plant pathogenic material can be resisted to include, such as ion channel blocking agent, such as The blocking agent of sodium and calcium channel, such as KP1, KP4 or the KP6 toxin of virus；Stilbene synthase, bibenzyl synthases；Chitinase；Glucan Enzyme；So-called " pathogenesis-related protein " (PRP, see, for example, EP-A-0 392 225)；Caused a disease by resisting caused by microorganism The skin antibioticses or heterocyclic antibiotics class (see, for example, WO 95/33818) that are related in material, such as plant pathogen defence or Protein or polypeptide factor (so-called " Plant Genes Conferring Resistance To Pathogens ", as described in WO 03/000906).
Crop can also increase (such as false single to fungi (such as reaping hook is mould, anthracnose or phytophthora), bacterium through modifying Born of the same parents bacterium) or viral (such as corium solani, tomato spotted wilf virus, cucumber mosaic virus) pathogen resistance.
Crop also includes those crops with the increased resistance to nematode (such as soybean cyst nematode).
Crop with the tolerance to abiotic stress for example passes through NF-YB or as known in the art including those Other protein expressions have the crop to the increased tolerance of arid, high salt, high temperature, cold, frost or light radiation.
Show the crop of increased yield or quality include those have improvement blooming or fruit maturation characteristic (such as is prolonged It is ripe late)；Oil, starch, amino acid, aliphatic acid, vitamin, phenols through modification or other inclusions (such as Wei Sidifu (Vistive)TMSoybean varieties)；Strengthen nutrien utilization (such as improveing nitrogen assimilation)；And enhancing quality plant product (such as The cotton fiber of higher quality).
According to other of the compound of the present invention and composition using field be the stored goods of protection and storeroom simultaneously And protection raw material, such as timber, textile, floor or building, and in hygiene department, especially protect the mankind, family Poultry and the livestock of fecund exempt from the harmful organism of mentioned type.
It is used to control harmful organism (such as Dulicidae and other disease vectors present invention also offers one kind；See also http://www.who.int/malaria/vector_control/irs/en/) method.In one embodiment, it is used for The method of control harmful organism is included by brushing, rolling, spraying, being coated or impregnated with, to the object noxious livings, their field Or surface or matrix apply the composition of the present invention.By way of example, (e.g., a kind of surface is contemplated by the present invention method Wall, ceiling or floor surface) IRS (indoor residual spray) apply.In another embodiment, it is contemplated that by such group Compound is applied to a kind of matrix, and such as nonwoven or textile material, the material is in mesh, coil serving, bed clothes, curtain and tent Form (or can be used in the manufacture of these articles using).
In one embodiment, for control such harmful organism method include to the object noxious livings, they Place or surface or matrix apply a kind of composition of the invention for killing harmful organism effective dose, in order in the surface or matrix What upper offer was effectively detained kills harmful organism activity.Such apply can be by brushing, rolling, spraying, being coated or impregnated with this Invention kills pest composition to carry out.By way of example, method of the invention contemplates a kind of surface (e.g., wall, ceiling Or floor surface) IRS apply, in order to provide on a surface be effectively detained kill harmful organism activity.At another In embodiment, it is contemplated that the control using such composition for a kind of delay of the harmful organism in matrix, the matrix It is that (or can be used for for instance in the form of mesh, coil serving, bed clothes, curtain and tent in the manufacture of these articles Using) textile material.
Pending processing matrix (including non-woven fleece, fabric or mesh) can be by natural fiber, e.g., cotton, rufiyaa Leaf fiber, jute, flax, sisal hemp, burlap or wool, or synthetic fibers, such as polyamide, polyester, polypropylene, polyacrylonitrile Etc. be made.Polyester is particularly suitable.The method of textile processing is known, such as WO 2008/151984, WO 2003/034823、US 5631072、WO 2005/64072、WO 2006/128870、EP 1724392、WO 2005113886 Or WO 2007/090739.
Other scopes according to the purposes of these compositions of the present invention are together with all kinds for all ornamental trees Fruit tree and nutwood tree injection/trunk process field.
In tree injection/trunk process field, according to these compounds of the present invention particularly suitable for confrontation from upper The Lepidoptera stated and the brill wood insect from coleoptera, especially resist the brill carpenter worm listed in following table AA and BB：
Table A A. has the example of the external brill carpenter worm of Economic Importance.
Table BB. has the example of this ground auger carpenter worm of Economic Importance.
It is to be directed to ectoparasite according to the compound of the present invention and composition in hygiene department, for example, it is hard tick, soft Tick, itch mite, harvest mite, fly (sting and lick), parasitic fly larvae, lice, head louse, bird lice and flea are effective.
The example of such parasite is：
Anoplura：Haematopinus, long palate Pediculus, Pediculus and Pthirus, pipe Pediculus.
Mallophaga：Filoplume Pediculus, short angle bird lice category, duck Pediculus, Bovicola, Werneckiella category, Lepikentron Category, Damalinia, Trichodectes and Felicola.
Diptera and Nematocera and Brachycera, such as Aedes, Anopheles, Culex, Simulium, Eusimulium, sand fly Category, Lutzomyia, Bitting midge, Chrysops, Hybomitra, Atylotus, Gadfly, Chrysozona, Philipomyia spp., honeybee hippoboscid Category, Musca, Hydrotaea, Genus Stomoxys, Haematobia, not fly category, Fannia, Glossina, Calliphora, Lucilia, Carysomyia, Wohlfahrtia, Sarcophaga, Oestrus, Hypoderma, Gasterophilus, Hippobosca, Lipoptena and Melophagus.
Siphonaptera, such as flea category, Ct, Xenosyllaspp, Ceratophyllus.
Heteroptera, such as Cimex, Triatoma, Rhodnius, Triatoma.
Blattaria, such as oriental cockroach, American cockroach, Groton bug and Supella.
Acari (mite section) and rear valve mesh and Mesostigmata, such as Argas, Ornithodoros, Otiobius, hard tick Category, Amblyomma, Boophilus, Dermacentor, Haemaphysalis, Hyalomma, Rh, Dermanyssus, the sharp mite category of thorn, lung thorn mite Category, chest thorn mite category and Varroa.
Axle Acarina (preceding valve suborder) and flour mite mesh (Astigmata), for example, honeybee shield mite category, Ji chela category, Ornithocheyletia, Mite category, wing mite under Myobia, Psorergates, Demodex, Trombidium, yak mite category, Tyroglyphus, Tyrophagus, Caloglyphus, neck Category, Psoroptes, Chorioptes, ear Sarcoptesspp, Sarcoptesspp, Notoedres, Knemidokoptes, Cytoleichus and Laminosioptes.
It is described according to the present invention these compounds and composition apply also for protection materials for example timber, textile, plastics, Adhesive, glue, paint vehicle, paper and card, leather, floor and building etc. are from insect infestations.
It can be used for for example resisting following harmful organism according to the composition of the present invention：Beetle, such as North America house longhorn beetle, length Hair longicorn, furniture death watch beetle, red hair death watch beetle, Ptilinus pectinicornis, the stem of noble dendrobium, loose bud branch death watch beetle, loose product death watch beetle, Lyctus brunneus Stephens, Africa Powder is moth-eaten, southern powder moth, quercitron moth, pubescence powder moth, chest powder moth, minthea rugicollis, material bark beetle category, wood strip bark beetle category, coffee it is black it is long it is moth-eaten, Long moth-eaten, the different wing of palm fibre of tree grows moth-eaten, Sinoxylon and dinoderus minutus；And hymenopterans insect, such as the big wood wasp of blue-black wood wasp, dragon spruce, Urocerus gigas toiganus and big wood wasp；And termite, such as European kalotermitid, numb head heap sand termite, the different termite of Indian-Pakistani structural wood, yellow chest Reticulitermes flavipe, Sang Te reticulitermes flavipes, reticulitermes flavipe, Mastotermes darwiniensis, Nevada Gu termite and coptotermes formosanus；And moth, such as silverfish.
Therefore, it is excellent the invention provides a kind of insecticidal, mite killing, nematicide or kill molluscan composition Selection of land is a kind of insecticidal or composition of mite killing, said composition include insecticidal, mite killing, nematicide or kill software The compound with Formula I of the effective dose of animal and a kind of carrier or diluent appropriate to its.
In terms of one other, the invention provides a kind of method resisted and control harmful organism, this method includes Insect, mite killing will be killed, kill nematode or kills mollusk effective dose, that preferably kills insect and mite killing effective dose has chemical formula It is on the scene that I compound or a kind of composition comprising the compound with Formula I are applied to harmful organism, harmful organism institute Institute, or be applied to easily by the plant of pest infestation, except one kind by operation or therapy for handling human body or animal body Method and the diagnostic method implemented to human body or animal body outside.
Compound with Formula I is preferred for resisting insect or mite.
Term " plant " as used herein includes seedling, shrub and trees.
The invention further relates to one kind to kill pest composition, and said composition is except including this change with Formula I Outside compound, in addition to a variety of preparation adjuvants.
Therefore the present invention is directed to kill pest composition, such as emulsifiable concentrate in polymeric agents, outstanding Supernatant liquid concentrate, direct sprayable or dilutable solution, the paste that can be smeared, dilute emulsion, soluble powder, dispersible powder Last, wettable powder, dust, particle or encapsulation, these are killed in the active component that pest composition is included according to the present invention At least one and be selected to be adapted to set objective and prevailing circumstances.
In these compositions, active component uses in a pure form, such as the solid active in a specific granularity Composition, or preferably together with least one of the auxiliary agent that is routinely used in preparation field, these auxiliary agents such as increment Agent, such as solvent or solid carrier, or such as surface active cpd (surfactant).
The example of suitable solvent is：Unhydrided or partially hydrogenated aromatic hydrocarbon, preferably C8 to the C12 of alkylbenzene Part, such as xylene mixture, alkylated naphthalene or tetrahydronaphthalene, aliphatic or cycloaliphatic hydrocarbon, such as paraffin or hexamethylene； Alcohol, such as ethanol, propyl alcohol or butanol；Glycol and its ether and ester, such as propane diols, dipropylene glycol, ethylene glycol or ethylene glycol list Methyl ether or ethylene glycol monoethyl ether；Ketone, such as cyclohexanone, isophorone or DAA；Intensive polar solvent, such as N- methylpyrroles Alkane -2- ketone, dimethyl sulfoxide or N,N-dimethylformamide, water；Unepoxidized or epoxidized vegetable oil, such as unepoxidized or ring Aoxidize rapeseed oil, castor oil, coconut oil or soybean oil and organic silicone oil.
It is typically ground natural minerals for such as solid carrier of dirt agent and dispersible powder, such as calcite, Talcum, kaolin, montmorillonite or attapulgite.In order to improve physical property, the silica or high degree of dispersion of high degree of dispersion are added Absorbable polymer is also possible.Suitable particulate adsorptive support for granule is porous type, such as float stone, brick Gravel, sepiolite or bentonite, and suitable non-sorptive carrier materials are calcite or sand.In addition it is possible to use a large amount of nothings The plant heels of the particulate material of machine or organic natural goods, particularly dolomite or crushing.
Depending on the type of active component to be prepared, suitable surface active cpd is nonionic, cationic And/or anionic surfactant or surfactant mixture, they emulsify, disperse and moistened spy with good Property.Surfactant mentioned below is considered merely as example；It is routinely being used in preparation field and suitable according to the present invention A large amount of other surfaces activating agents be described in pertinent literature.
Suitable nonionic surface active agent especially aliphatic or cycloaliphatic alcohol, saturation or unrighted acid or The polyglycol ether derivative of alkyl phenol, these derivatives can include about 3 to about 30 ethylene glycol ether groups and About 8 to about 20 carbon atoms in (ring) aliphatic hydrocarbon groups or about 6 to about 18 in the moieties of alkyl phenol Carbon atom.Also suitably water-soluble polyethylene oxide and polypropylene glycol, second diaminourea polypropylene glycol or alkyl polypropylene glycol Adduct, these adducts have 1 to about 10 carbon atom and about 20 to about 250 ethylene glycol ethers in alkyl chain Group and about 10 to about 100 propylene glycol ether groups.Generally, each propylene glycol units of above-claimed cpd include 1 to about 5 second Diol units.It can be mentioned that example be nonylphenoxy polyethoxy ethanol, castor oil polyglycol ether, polypropylene glycol/poly- Ethylene oxide adduct, tributyl phenoxypolyethoxy ethanols, polyethylene glycol or octylphenoxy polyethoxy ethanol.It is also suitable Suitable is the fatty acid ester of polyoxy ethene anhydro sorbitol, such as polyethenoxy sorbitan trioleate.
Cationic surface active agent especially generally has at least one alkyl residue (about 8 to about 22 C originals Son) as substituent and (non-halogenated or halogenation) low alkyl group or hydroxy alkyl or benzyl residue conduct be further substituted with base Quaternary ammonium salt.These salt are preferably in the form of halide, Methylsulfate or sulfovinate.Example is stearyl front three Ammonium chloride and double (2- chloroethyls) the ethyl phosphonium bromide ammoniums of benzyl.
The example of suitable anionic surfactant is the surface-active chemical combination of water-soluble soaps or water-soluble synthesis Thing.The example of suitable soaps be the alkali metal salt of the aliphatic acid with about 10 to about 22 C atoms, alkali salt or (unsubstituted or substituted) ammonium salt, such as oleic acid or stearic sodium salt or sylvite or for example from coconut or tall oil The sodium salt or sylvite of obtainable natural acid mixture；Fatty acid methyltaurinates must also be mentioned that.However, more Conventional is the surfactant of synthesis, particularly Fatty sulphonates, fat sulphate, the benzimidizole derivatives or alkane of sulfonation Base arylsulphonate.Generally, Fatty sulphonates and fat sulphate are with alkali metal salt, alkali salt or (substituted or not It is substituted) ammonium salts are existing and these salt generally have the alkyl of about 8 to about 22 C atoms, and alkyl is also answered This is interpreted as the moieties for including acyl group；It can be mentioned that example be lignin sulfonic acid, laurilsulfate or from natural The sodium salt or calcium salt of fatty alcohol sulphuric acid ester admixture prepared by aliphatic acid.The group also includes fatty alcohol/ethylene oxide adduct Thioesters salt and sulfonate.The benzimidizole derivatives of these sulfonation preferably comprising 2 sulfonyls and have about 8 to about 22 C The fatty acid residue of atom.The example of alkylaryl sulfonates is decylbenzenesulfonic acid, dibutyl naphthalenesulfonic acid or naphthalene sulfonic acids/formaldehyde contracting Sodium, calcium or the tri ethanol ammonium salt of compound.Furthermore, it is also possible that suitable phosphate, such as nonylphenol/(4-14) epoxy The phosphate ester salt of ethane adduct, or phosphatide salt.Other suitable phosphate is the three of phosphoric acid and aliphatic or aromatic alcohols Ester and/or alkyl phosphoric acid and aliphatic or the diester of aromatic alcohols, the two is all efficient oil type adjuvant.These three esters have been described above In such as WO 01/47356, WO 00/56146, EP-A-0579052 or EP-A-1018299 or under its chemical name It is commercially available.Preferred phosphotriester for these new compositions is tricresyl phosphate-(2- ethylhexyls) ester, tricresyl phosphate n-octyl And three butoxy ethyl ester of phosphoric acid, wherein tricresyl phosphate-(2- ethylhexyls) ester is most preferred.Suitable alkyl phosphonic acid dibasic acid esters It is double-(2- ethylhexyls)-(2- ethylhexyls) esters of phosphonic acids, phosphonic acids pair-(2- ethylhexyls)-(n-octyl) ester, the fourth of phosphonic acids two Base-butyl ester and double (2- the ethylhexyls)-Sanya propyl diesters of phosphonic acids, wherein double-(2- ethylhexyls)-(n-octyls)-of phosphonic acids Ester is particularly preferred.
A kind of additive preferably can be additionally included according to these compositions of the present invention, the additive includes plant The oil of source or animal origin, mineral oil, these oily Arrcostabs or these oily and oily derivative mixtures.According to this hair The value of the oil additive used in bright composition is generally the 0.01% to 10% of the spraying mixture.For example, The oil additive can be being added in aerosol can with desired concentration after prepared by the spraying mixture.Preferable oil Oil of the additive including mineral oil or plant origin, such as rapeseed oil (such asAnd), olive oil Or sunflower oil, the vegetable oil of emulsification, such as(Luo Na-Planck Canada Company ( Canada Inc.)), the oily Arrcostab of plant origin, such as methyl-derivatives, or the oil of animal origin, such as fish oil or ox Fat.A kind of preferable additive includes such as by weight substantially 80% fish oil Arrcostab and by weight 15% first Base rapeseed oil and also by weight 5% conventional emulsifying agent and pH change agent as active component.It is especially preferred Oil additive includes C8-C22The Arrcostab of aliphatic acid, especially C12-C18The methyl-derivatives of aliphatic acid, such as it is important that the moon The methyl ester of cinnamic acid, palmitic acid and oleic acid.Those esters are referred to as methyl laurate (CAS-111-82-0), methyl hexadecanoate And methyl oleate (CAS-112-62-9) (CAS-112-39-0).A kind of preferable fatty acid methyl ester derivant is 2230 and 2231 (Kening Co., Ltd (Cognis GmbH)).Those and other oily derivatives are also known in herbicide adjuvant guiding principle Want (Compendium of Herbicide Adjuvants), the 5th edition, southern University of Illinois, 2000.In addition, alkoxylate Aliphatic acid can be used as the additive in the present composition as the additive based on polymethyl siloxane, based on poly- first The additive of radical siloxane is described in WO 2008/037373.
The application and effect of these oil additives can by by they and surface reactive material, such as nonionic, Anionic or cationic surface active agent are combined and further improved.Suitable anion, nonionic and cation form The example of face activating agent is listed in WO 97/34485 page 7 and 8.Preferable surface reactive material is dodecane benzyl sulfonic acid The anion surfactant of salt type, especially its calcium salt, and the also nonionic table of fatty alcohol ethoxylate type Face activating agent.Particularly preferably ethoxylation degree is 5 to 40 C12-C22Fatty alcohol.The example of commercially available surfactant It is Genapol types (Clariant spy company (Clariant AG)).Further preferably organic silicon surfactant, it is especially poly- The heptamethyltrisiloxane of alkyl-oxide-modification, it is commercially available, for example, SilwetIt is and fluoridized Surfactant.The concentration of surface reactive material is generally from 1% to 30% by weight relative to total body additives.By oil The example for the oil additives that the mixture of class or mineral oil or derivatives thereof and surfactant is formed is Edenor ME(Syngenta Co., Ltd (Syngenta AG, CH)) and(BP ligroins state is limited Company (BP Oil UKLimited, GB)).
The surface reactive material can also be used individually in preparation, that is to say, that without oil additive.
It can aid in further in addition, adding a kind of organic solvent into the oil additive/surfactant mixture Humidification.Suitable solvent is for exampleAnd Aromatic solvents (ESSO)(Exxon Corporation (Exxon Corporation)).The concentration by weight of such solvent can be gross weight from 10% to 80%.This kind of oil additive can To be mixed with solvent, and described in such as US-A-4834908.A kind of name of the commercially available oil additive wherein disclosed Referred to as(BASF AG (BASF Corporation)).It is according to currently preferred another oil additive(first just reaching branch company of crop protection Canada (Syngenta Crop Protection Canada)).
Except these oil additives listed above, in order to strengthen the activity of these compositions according to the present invention, also have May by alkyl pyrrolidone (such as) preparation be added in the spraying mixture.Synthesis can also be used Latex (such as polyacrylamide, polyvinyl compound or poly- 1-p-menthene (such asOr)) preparation.Solution comprising propionic acid, such as EurogkemThe spray can also be mixed into Spill and active reinforcing agent is used as in mixture.
Term " active component " refers to the one kind for having in these compounds of Formula I, especially especially in these tables The compound with Formula I of middle disclosure.It also refers to the compound with Formula I, and (particularly one kind is in the table 1 Compound) mixture with other insecticides, fungicide, herbicide, safener, adjuvant etc., these mixtures are specific It is such as described below.
These compositions can also include other solids or liquid adjuvants, such as stabilizer, such as unepoxidized or epoxy Change vegetable oil (such as epoxidised coconut oil, rapeseed oil or soybean oil)；Defoamer, such as organic silicone oil；Preservative；Viscosity is adjusted Save agent；Bonding agent and/or tackifier；Fertilizer, especially formulation fertilizer containing nitrogen, such as the ammonium nitrate as described in WO 2008/017388 And urea, the effect of these fertilizer can strengthen the compounds of this invention；Or for realizing the other active components of specific function, example Such as ammonium salt Huo phosphonium salts, especially halide, sulfuric acid (hydrogen) salt, nitrate, carbonic acid (hydrogen) salt, citrate, tartrate, formic acid Salt and acetate, as described in WO 2007/068427 and WO 2007/068428, these salt can also strengthen of the present inventionization The effect of compound and it can be applied in combination with the penetration enhancer of such as alkoxylated fatty acid；Bactericide, fungicide, Nematicide, activating plants agent, invertebrate poison or herbicide.
Composition according to the present invention is with a kind of per se known manner, in the case of in the absence of auxiliary agent, such as is led to Cross grinding, screening and/or compression solid active component；With in the presence of at least one auxiliary agent, such as pass through close mixed active Composition grinds active component to prepare with a kind of or some auxiliary agents and/or together with a kind of or some auxiliary agents.
The application process of these compositions, it is the method for the harmful organism for controlling the above-mentioned type, such as spraying, atomization, spreads Powder, brush, coating, broadcast sowing or pour-they be chosen so as to be suitable to common situation expected purpose-and these compositions be used for The purposes for controlling the harmful organism of the above-mentioned type is other themes of the present invention.Typical concentration ratio be 0.1ppm with Between 1000ppm, the active component preferably between 0.1ppm and 500ppm.
In crop protection field, preferable application process is to be applied to the leaf (foliar spray medicine) of these plants, it is possible to Frequency and the ratio for selecting to apply infect risk with meet mentioned harmful organism.Alternately, the active component can be with By root system unite (systemic action) reach plant, this be the location of these plants is impregnated with by using a kind of fluid composition or Person by the location of the active component introduced plant of solid form by (such as introducing soil, such as the shape with particle (soil application) Formula) come what is realized.In the case of rice crop, such granule can add in the rice field of waterflooding measuredly.
According to these compositions of the present invention be further adapted for plant propagation material protection (such as seed, as fruit, stem tuber or Seed, or nursery plants) confrontation the above-mentioned type harmful organism.The propagating materials can be located before planting with these compositions Reason, such as seed can be handled prior to seeding.Alternately, these compositions can be applied to seed benevolence (coating), Huo Zhetong Cross and these benevolence are soaked in fluid composition or by applying one layer of solid composite.When the propagating materials is planted at When, it is also possible to these compositions are applied into seeded furrow for example during drilling.These processing methods of plant propagation material and Plant propagation material including a kind of compound as defined above with chemical formula (I) is other themes of the present invention.
According to other application processes of these compositions of the present invention soil, the portion of dipped plants are administered to including instillation Point, such as ball stem or stem tuber, it is impregnated with soil and soil injection.These methods are that oneself knows in this area.
In order to apply the compound with Formula I as insecticide, acaricide, nematicide or invertebrate poison To place where a kind of harmful organism, one of harmful organism or it is administered to easily by a kind of a kind of plant of pest infestation, Compound with Formula I is usually formulated as a kind of composition, and said composition, which is removed, includes this chemical combination with Formula I Outside thing, in addition to a kind of suitable inert diluent or carrier, and optionally, exist as the described herein or for example A kind of preparation adjuvant in surfactant (SFA) form described in EP-B-1062217.SFA is can be by reducing boundary Face tension force modification interface (such as liquid/solid, liquid/gas or liquid/liquid interface) characteristic and thus cause other characteristics (such as it is scattered, Emulsification and moistening) change chemicals.
Under normal circumstances, these compositions include the work of the Formula I of 0.1% to 99% (especially 0.1% to 95%) At least one solid or liquid adjuvant of property composition and 1% to 99.9% (especially 5% to 99.9%), however, it would be possible to 0 to 25% (especially 0.1% to 20%) for being said composition is surfactant (% expressions weight percent in each case Than).Although for commodity, the composition of concentration is typically preferable, and terminal user is substantial usually using having The diluted composition of the active component of lower concentration.
Typical concentration amount is the active component preferably between 0.1 and 500ppm between 0.1 and 1000ppm.Often The amount of application of public item generally arrives 1000g/ha per public item 1 to 2000g active components, especially 10, and preferably 10 arrive 600g/ ha。
When in a kind of seed dressing in use, the compound with Formula I is with every kilogram of seed 0.0001g to 10g (examples Such as 0.001g or 0.05g), preferably 0.005g to 10g, more preferably 0.005g to 4g ratio use.
Preferable seed treatment premix preparation is aqueous suspension concentrate.The preparation can use conventional processing skill Art and machine, such as fluidization, roller Ginding process, static rotation (rotostatic) subprocessors and rotary drum Coating device is administered on seed.Other method, such as spouted bed can also be useful.These seeds can be in the advance of coating The pre- classification of row.After coating, by these seeds typically be carried out drying and be then transferred into a starching machine be used for Starch (sizing).Such method is well known in the art.
These compositions can be selected from multiple preparation types, including can dirt powder (DP), soluble powder (SP), water Soluble particles (SG), water dispersibles particle (WG), wettable powder (WP), particle (GR) (slowly or quick release), solubility The miscible liquid (OL) of concentrate (SL), oil, ultra low volume liquids (UL), emulsifiable concentrate (EC), dispersibles concentrate (DC), emulsion (both oil-in-water (EW) and Water-In-Oil (EO)), microemulsion (ME), suspension-concentrates (SC), hanging based on oil Supernatant liquid concentrate (OD), aerosol, mist formation/smog preparation, capsule suspension liquid (CS) and seed treatment preparation.Any In the case of, selected preparation type by depending on contemplated specific purposes and with Formula I compound thing Reason, chemistry and biological nature.
Can dirt pulvis (DP) can be by by the compound with Formula I and one or more solid diluent (examples Such as, natural clay, kaolin, pyrophyllite, bentonite, aluminum oxide, montmorillonite, diatomite (kieselguhr), chalky soil, diatom Native (diatomaceous earths), calcium phosphate, calcium carbonate and magnesium carbonate, sulphur, lime, flour, talcum and other organic and nothings The solid carrier of machine) mix and the mixture is mechanically milled into fine powder to prepare.
Soluble powder (SP) can be by by the compound with Formula I and one or more water-soluble inorganic salts (such as sodium acid carbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as polysaccharide) and it is optionally a kind of or The mixture of a variety of wetting agents, one or more dispersants or the reagent is mixed to prepare to improve water dispersible/water Dissolubility.Then the mixture is ground into fine powder.Similar composition grain can also be formed water-soluble granular (SG)。
Wettable powder (WP) can be by by the compound with Formula I and one or more solid diluents or load Body, one or more wetting agents and preferably, one or more dispersants, and preferably, one or more suspending agents Mix to prepare to promote in a liquid scattered.Then the mixture is ground into fine powder.Can also be by similar combination Composition granule is to form water-dispersible granular material (WG).
It may be formed so that granule (GR)：By by the compound with Formula I and one or more powdery solids The mixture pelleting of diluent or carrier is formed, or by the way that by the compound with Formula I, (or it is in a kind of suitable examination Solution in agent) it is absorbed into honeycombed grain material (such as float stone, Concave-convex clay rod, bleaching earth, diatomite (kieselguhr), diatomite (diatomaceous earths) or maize cob meal), or by by the chemical combination with Formula I Thing (or its solution in Suitable agents) is adsorbed onto hard core material (such as sand, silicate, mineral carbonic acid salt, sulfate or phosphorus Hydrochlorate) on and if necessary, be dried to be formed by preforming blank granules.Help is commonly used to absorb or inhale Attached reagent includes solvent (such as aliphatic and aromatic petroleum solvent, alcohol, ether, ketone and ester) and sticker is (such as poly- Vinyl acetate, polyvinyl alcohol, dextrin, sugar and vegetable oil).Other one or more additives can also be included in particle (such as emulsifying agent, wetting agent or dispersant).
Dispersibility concentrate (DC) can be by being dissolved in water or a kind of organic solvent by the compound with Formula I Prepared in (such as ketone, alcohol or glycol ether).These solution can include surfactant (such as being improved in spray cistern Water-thinned prevents from crystallizing).
Emulsifiable concentrate (EC) or oil-in-water emulsion (EW) can be by being dissolved in one by the compound with Formula I In kind organic solvent (mixture for optionally including one or more wetting agents, one or more emulsifying agents or the reagent) To prepare.Being suitable for EC organic solvent class includes aromatic hydrocarbon (such as alkyl benzene or alkyl naphthalenes, example SOLVESSO 100th, SOLVESSO 150 and SOLVESSO 200；SOLVESSO is a registration mark), ketone (such as cyclohexanone or methyl ring Hexanone) and alcohol (such as benzyl alcohol, furfuryl alcohol or butanol),
N- alkyl pyrrolidines ketone (such as 1-METHYLPYRROLIDONE or NOP), the dimethylformamide of aliphatic acid Class (such as C8-C10Fatty acid dimethylamides) and chlorinated hydrocabon.EC products can spontaneously emulsify when added in water, produce With sufficiently stable property to allow the emulsion being spray applied by appropriate equipment.EW preparation is related to acquisition and is used as a kind of liquid (if it is not liquid at room temperature, and it can melt under typically lower than 70 DEG C of reasonable temperature) or in solution The compound with Formula I of (by the way that it is dissolved in appropriate solvent), then under high shear by gained liquid or molten Liquid is emulsified into the water comprising one or more SFA, to produce emulsion.The suitable solvent used in EW include vegetable oil, Chlorinated hydrocabon (such as chlorobenzene), aromatic solvent (such as alkylbenzene or alkylnaphthalene) and other in water appropriate with low solubility Organic solvent.
Microemulsion (ME) can be by the way that water be mixed to make with the admixture of one or more solvents and one or more SFA It is standby, spontaneously to produce a kind of thermodynamically stable isotropic liquid formulations.Compound with Formula I is at the beginning Be present in water or solvent/SFA admixtures in.The suitable solvent used in ME includes previously described in EC or EW Those used.ME can be that (which kind of system be present can be by conductivity measurement come really for oil-in-water system or water-in-oil system It is fixed) and can be suitable for mixing water miscible and oil-soluble pesticides in identical preparation.ME is adapted to use In being diluted into water, remain microemulsion or form conventional oil-in-water emulsion.
Suspension-concentrates (SC) can include a kind of insoluble solids of the fine dispersion of the compound with Formula I The water-based or non-aqueous suspensions of grain.SC can by by the solid chemical compound with Formula I optionally with it is a kind of or more Prepared by kind of dispersant ball milling or bead mill in appropriate medium, to produce the fine grained suspension of the compound.In said composition In can include one or more wetting agents, and suspending agent can be included to reduce the sinking speed of particle.Alternately, may be used With compound of the dry grinding with Formula I and it is added in the water comprising previously described reagent, with desired by generation Final product.
Oil-based suspension concentrate (OD) can be similarly by by the insoluble of the compound with Formula I of fine dispersion Property solid particle, which is suspended in a kind of organic fluid (for example, at least a kind of mineral oil or vegetable oil), to be prepared.OD can enter one Step includes at least one penetration enhancers (such as a kind of alcohol ethoxylate or a kind of related compound), at least one nonionic Type surfactant and/or at least one anionic surfactant, and optionally at least a kind of addition from the following group Agent, the group have emulsifying agent, foam in hibitors, preservative, antioxidant, dyestuff and/or inert fill material.OD is to want And be diluted with water before the use to produce a kind of spray solution with sufficiently stable property, so as to allow to pass through Appropriate equipment is spray applied.
Aerosol formulations include compound and suitable propellant (for example, normal butane) with Formula I.Can also By the compound with Formula I be dissolved or dispersed in suitable medium (such as water or can be miscible with a kind of water liquid, such as just Propyl alcohol) in provide the composition that is used in non-pressurized spread by hand pump.
Compound with Formula I can mix with firework mixture to form a kind of be applied in the dry state The composition of the smog comprising the compound is produced in closing space.
Capsule suspension liquid (CS) can be by prepare, except additional polymerization with preparing EW preparations similar mode Outside step, so that obtain the aqueous dispersion of oil droplet, have wherein each oil droplet is wrapped up and contained by polymer shell A kind of compound of Formula I and its optional a kind of carrier or diluent.The polymer shell can pass through interfacial polycondensation Reaction is produced by condensing program.These compositions can provide the controlled release of this compound with Formula I And they can be used for seed treatment.Compound with Formula I can also be formulated in biodegradable polymer In matrix, to provide the slow controlled release of the compound.
Compound with Formula I can also be formulated to use as seed treatment, such as powder combinations Thing, including the powder (DS) for dry method seed treatment, water miscible powder (SS) or dispersible for the water of slurry processing Powder (WS) is used as a kind of fluid composition, including flowable concentrate (FS), a kind of solution (LS) or a kind of capsule to hang Supernatant liquid (CS).DS, SS, WS, FS and LS composition preparation respectively with DP, SP, WP, SC and DC composition described above that It is a little very similar.Composition for handling seed can include a kind of examination for assisting said composition to be attached on the seed Agent (such as a kind of mineral oil or a kind of film forming obstacle).
It is (such as logical to improve the biological property of said composition that the composition of the present invention can include one or more additives Cross wetability, delay or the distribution improved on surface；Rain fastness on surface through processing；Or the compound with Formula I Absorption and mobility).These additives include surfactant (SFA), oil base spray additives, such as some mineral oil, Vegetable oil or crude vegetal (such as soybean oil and rapeseed oil), and they strengthen with other biological adjuvant (can aid in or Change have the function that Formula I compound composition) blend.Can for example, by adding ammonium salt He/Huo phosphonium salts, And/or optionally at least one such as fatty alcohol alkoxy compound (such as rapeseed methylester) or the penetration enhancer of vegetable oil esters The effect of to improve the compound with Formula I.
Wetting agent, dispersant and emulsifying agent can be cationic, anionic, amphoteric or non-ionic surface Activating agent (SFA).
Suitable cationic SFA include quaternary ammonium compound (such as cetyl trimethylammonium bromide), imidazoline and Amine salt.
Salt (such as the bay sulfuric acid of suitable anionic SFA including aliphatic acid alkali metal salt, analiphatic sulphur acid monoester Sodium), the salt of the aromatic compound of sulfonation (such as neopelex, calcium dodecyl benzene sulfonate, butyl naphthalene sulfonate And the mixture of two-isopropyl-sodium naphthalene sulfonate and three-isopropyl-sodium naphthalene sulfonate), ether sulfate, ether alcohol sulfate (such as Laureth -3- sodium sulphate), ether carboxylate (such as laureth -3- carboxylic acid sodiums), phosphoric acid ester is (from a kind of or more Kind fatty alcohol and phosphoric acid (mainly monoesters) or the product reacted between phosphorus pentoxide (mainly diester), such as laruyl alcohol With the reaction between four phosphoric acid；These other products can be ethoxylated), sulfosuccinic acid amides hydrochlorate, paraffin or alkene sulphur Hydrochlorate, taurate and ligninsulfonate.
Suitable amphoteric SFA includes glycine betaine, propionate and glycinate.
The SFA of the suitable non-ionic type include alkylene oxides (such as oxirane, expoxy propane, epoxy butane or Its mixture) with aliphatic alcohols (such as oleyl alcohol or cetanol) or with alkylbenzene phenols (such as octyl phenol, nonyl phenol or pungent Base cresols) condensation product；The partial ester of derivation of self-long chain aliphatic acid or hexitan；The condensation production of the partial ester and oxirane Thing；Block polymer (includes oxirane and expoxy propane)；Alkanolamide；Monoesters (such as fatty acid polyethylene glycol ester)；Oxygen Change amine (such as lauryl dimethyl amine oxide)；And lecithin.
Suitable suspending agent include hydrophilic colloid (such as polysaccharide, polyvinylpyrrolidone or sodium carboxymethylcellulose) and Expansive clay (such as bentonite or attapulgite).
Compound with Formula I can be applied by the means that harmful organism compound is killed in any administration that oneself knows With.For example, it can (preparation or not preparing) be directly applied to these harmful organisms or the place of these harmful organisms Place (such as the habitat of these harmful organisms, or easily by the planting plants of pest infection), or it is applied to appointing for plant What part, including leaf, stem, branch or root, the seed being applied to before plantation, be applied to plant growing or by planted its His medium (planting system that such as soil in root week, normal soil, paddy field water or water are planted), or it can spray, dusting, pass through Dipping is applied, and is applied as butterfat or paste preparation, applied as steam or by by composition (such as particulate composition or Wrap composition in water-soluble bag) distribution or and apply in burying or in aqueous environments.
Compound with Formula I can also be injected into plant or with electrodynamic spraying techniques or other low volume methods It is sprayed on plant, or is applied by soil or aerial irrigation systems.
Composition as aqueous formulation (aqueous solution or dispersion) is generally with the concentration containing a high proportion of active component The form of thing provides, and the concentrate is added to the water before the use.These concentrates can include DC, SC, OD, EC, EW, ME, SG, SP, WP, WG and CS, it usually needs be able to take to store and after such storage, can be added to for a long time To form aqueous formulation in water, these aqueous formulations keep homogeneous duration to be enough to set by the sprinkling of routine It is standby to apply.Such a aqueous formulation can include the compound with Formula I of variable quantity (for example, by weight 0.0001% To 10%), this depends on the purpose that they are used for it.
Compound with Formula I can with fertilizer (such as it is nitrogenous, containing potassium or phosphorous fertilizer, and more particularly It is ammonium nitrate and/or urea fertilizer) it is used in mixed way.Suitable preparation type includes fertiliser granulates.These mixtures are compatibly Include by weight up to 25% compound with Formula I.
In particular it is preferred to composition composition it is following (%=percentage by weights)：
Emulsifiable concentrate：
Active component：1% to 95%, preferably 5% to 20%
Surfactant：1% to 30%, preferably 10% to 20%
Solvent：5% to 98%, preferably 70% to 85%
Dirt agent：
Active component：0.1% to 10%, preferably 0.1% to 1%
Solid carrier：99.9% to 90%, preferably 99.9% to 99%
Suspension-concentrates：
Active component：5% to 75%, preferably 10% to 50%
Water：94% to 24%, preferably 88% to 30%
Surfactant：1% to 40%, preferably 2% to 30%
Wettable powder：
Active component：0.5% to 90%, preferably 1% to 80%
Surfactant：0.5% to 20%, preferably 1% to 15%
Solid carrier：5% to 99%, preferably 15% to 98%
Granule：
Active component：0.5% to 30%, preferably 3% to 15%
Solid carrier：99.5% to 70%, preferably 97% to 85%
Preparating example：
" Mpt. " refer to by DEG C in terms of fusing point.Free basis representation methyl group.
LCMS methods：
Method (SQD13)
Spectrum is recorded on the mass spectrograph from Waters (the mono- quadrupole mass spectrometers of SQD), and it is equipped with a kind of electricity Injection source (polarity：Cation or anion, capillary voltage：3.00kV, taper hole scope：30-60V, extractor：2.00V source Temperature：150 DEG C, desolvation temperature：350 DEG C, taper hole gas flow：0L/Hr, desolvation gas flow：650L/Hr, matter Measure scope：100 to 900Da) and a kind of Acquity UPLC from Waters：Binary pump, heat column compartment and two poles Pipe array detector.Solvent degasser, binary pump, heat column compartment and PDAD.Post：This UPLC of water HSS T3,1.8μm, 30x 2.1mm, temperature：60 DEG C, DAD wave-length coverages (nm)：210 to 500, Solvent Gradient：A=water+5% MeOH+0.05%HCOOH, B=acetonitrile+0.05%HCOOH：Gradient：Gradient：0min 0%B, 100%A；1.2-1.5min 100%B；Flow (ml/min) 0.85
Method (ZCQ13)：
Mass spectrogram is recorded on the mass spectrograph from Waters (Waters) (the mono- quadrupole mass spectrometers of ZQ), and it is equipped There is a kind of electrospray source (polarity：Cation or anion, capillary voltage：3.00kV, taper hole scope：30-60V, extractor： 2.00V source temperature：150 DEG C, desolvation temperature：350 DEG C, taper hole gas flow：0L/Hr, desolvation gas flow： 650L/Hr, mass range：100 to 900Da) and a kind of Acquity UPLC from Waters：Binary pump, heated beam Room and PDAD.Solvent degasser, binary pump, heat column compartment and PDAD.Post：It is fertile Special this UPLC HSS T3,1.8μm, 30x 2.1mm, temperature：60 DEG C, DAD wave-length coverages (nm)：210 to 500, Solvent Gradient：A =water+5%MeOH+0.05%HCOOH, B=acetonitrile+0.05%HCOOH：Gradient：Gradient：0min 0%B, 100%A；2.7- 3.0min 100%B；Flow (ml/min) 0.85.
Method (ZDQ13)：
Mass spectrogram is recorded on the mass spectrograph from Waters (Waters) (the mono- quadrupole mass spectrometers of ZQ), and it is equipped There is a kind of electrospray source (polarity：Cation or anion, capillary voltage：3.00kV, taper hole scope：30-60V, extractor： 2.00V source temperature：150 DEG C, desolvation temperature：350 DEG C, taper hole gas flow：0L/Hr, desolvation gas flow： 650L/Hr, mass range：100 to 900Da) and a kind of Acquity UPLC from Waters：Binary pump, heated beam Room and PDAD.Solvent degasser, binary pump, heat column compartment and PDAD.Post：It is fertile Special this UPLC HSS T3,1.8μm, 30x 2.1mm, temperature：60 DEG C, DAD wave-length coverages (nm)：210 to 500, Solvent Gradient：A =water+5%MeOH+0.05%HCOOH, B=acetonitrile+0.05%HCOOH：Gradient：Gradient：0min 0%B, 100%A；1.2- 1.5min 100%B；Flow (ml/min) 0.85.
Method (ZQ2000)：
ZQ2000 mass spectrographs (single-phase QMS) from water this (Waters)
Ionization method：Electron spray
Polarity：Cation
Capillary (kV) 3.5, taper hole (V) 60.00, extractor (V) 3.00, source temperature (DEG C) 150, desolvation temperature (DEG C) 350, taper hole blowback air-flow (L/Hr) 50, desolventizing air-flow (L/Hr) 800
Mass range：140 to 800Da
DAD wave-length coverages (nm)：210 to 400
Method：Use this ACQUITY UPLC of the water of following HPLC gradient conditions
(solvent orange 2 A：Water/methanol 9:1,0.1% formic acid, and solvent B：Acetonitrile, 0.1% formic acid)
Post type：This (Waters) ACQUITY UPLC HSS T3 of water；Column length：30mm；Column internal diameter：2.1mm；Particle Size：1.8 micron；Temperature：60℃.
1H and19F NMR are measured：Measured on Brucker 400MHz or 300MHz mass spectrographs, relative to TMS standards with Ppm provides chemical shift.The measure spectrum in specified solution.
Mass spectrometry method MS
LC-20AD mass spectrographs (single QMS) from Shimadzu (Shimadzu)
Instrument parameter：
Ionization method：Electron spray
Polarity：Cation and anion
Capillary (kV) 1.50
Taper hole (V) is unknown
Extractor (V) 5.00
Source temperature (DEG C) 200
Desolventizing temperature (DEG C) 250
Taper hole blowback air-flow (l/Hr) 90
Desolventizing air-flow (l/Hr) 90
Mass range：50Da to 1000Da
Example P1：2- methyl -7- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] -4- (trifluoros Methyl) -2,3- dihydrobenzo thiophene 1,1- dioxide (compound A1.014-B2.022)：
Step A：2- methyl-N- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] -1,1- dioxos -4- (three Methyl fluoride) -2,3- dihydrobenzo thiophene -7- formamides：
By 2- methyl isophthalic acids, 1- dioxos -4- (trifluoromethyl) -2,3- dihydrobenzo thiophene -7- carboxylic acids (308mg, 1.05mmol, as prepared in WO 9909023) and N2- methyl -5- (trifluoromethyl) pyridines -2,3- diamines (200mg, 1.05mmol, as prepared in WO 2012/092051) suspension 3- (ethylimino methylenes in THF (15ml) Base amino)-N, N- dimethyl -propyl- 1- amine (487mg, 3.14mmol) and pyridine (100mg, 1.26mmol) processing.This is reacted Mixture is stirred 18 hours and then diluted with ethyl acetate and 1N HCl.Separation organic phase simultaneously extracts aqueous phase with ethyl acetate Take.The organic phase of merging is washed with water, uses anhydrous Na2SO4Dry, filter and be concentrated under vacuum.Pass through flash chromatography (use ethyl acetate:Hexamethylene 1:1 elution), provide the title product (105mg, 21%) of white solid-like.LCMS (methods SQD13)：468 (M+H), retention time 0.97min.
Step B：2- methyl -7- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] -4- (fluoroforms Base) -2,3- dihydrobenzo thiophene 1,1- dioxide (compound A1.014-B2.022)：
By 2- methyl-N- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] -1,1- dioxo -4- (fluoroforms Base) -2,3- dihydrobenzo thiophene -7- formamides (71mg, 0.15mmol) and toluene-4-sulfonic acid (8mg, 0.05mmol) be dissolved in Solution in 1- methylpyrrolidin- 2- ketone (1ml) heats 100min in microwave at 160 DEG C.At this moment after, the reaction is mixed Compound is poured into water, is extracted with ethyl acetate, and uses anhydrous Na2SO4Dry, filter simultaneously reduced under vacuum.The product of acquisition is used Hexamethylene is ground, to provide mpt.206 DEG C of white solid-like of title compound (45mg, 66%).LCMS (methods SQD13)：450 (M+H), retention time 0.99min.
1H NMR(400MHz,CDCl3) ppm 8.77 (d, J=1.5Hz, 1H)；8.42 (d, J=1.5Hz, 1H)；8.05 (d, J=8.1Hz, 1H)；7.75 (d, J=7.1Hz, 1H)；3.90(s,3H)；3.74 (d, J=16.9,8.1Hz, 1H) 3.52- 3.68 (m, 1H) 3.19 (dd, J=16.87,8.1Hz, 1H)；1.55ppm (d, J=7.0Hz, 3H).
Example P2：The bromo- 2- methyl -7- of 4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] -2, 3- dihydrobenzo thiophene 1,1- dioxide (compound A1.014-B2.023)：
Step A：The bromo- 2- methyl-N- of 4- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] -1,1- dioxos - 2,3- dihydrobenzo thiophene -7- formamides：
At room temperature, by the bromo- 2- methyl isophthalic acids of 4-, 1- dioxo -2,3- dihydrobenzo thiophene -7- carboxylic acids (320mg, 1mmol, as prepared in WO 9909023) solution in dichloromethane (10ml) is with oxalyl chloride (170mg, 1.3mmol) With 1-2 drop DMF processing.After 1 hour, add N2- methyl -5- (trifluoromethyl) pyridines -2,3- diamines (200mg, 1.0mmol) and triethylamine (100mg, 1.2mmol), and the reactant mixture is stirred at room temperature until reaction is completed.This is anti- Mixture dchloromethane is answered, is washed with water, uses anhydrous Na2SO4Dry, filter and be concentrated under vacuum.Pass through fast layer Analysis purifying (uses ethyl acetate:Hexamethylene 1:1 elution), to provide the title compound (240mg, 48%) in yellow solid. LCMS (method SQD13)：478/480 (M+H), retention time 0.95min.
Step B：The bromo- 2- methyl -7- of 4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] -2,3- Dihydrobenzo thiophene 1,1- dioxide (A1.014-B2.023)
By the bromo- 2- methyl-N- of 4- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] -1,1- dioxos -2,3- Dihydrobenzo thiophene -7- formamides (210mg, 0.44mmol) and toluene-4-sulfonic acid (23mg, 0.13mmol) are dissolved in 1- methyl Solution in pyrrolidin-2-one (3ml) heats 1 hour in microwave at 160 DEG C.At this moment after, the reactant mixture is inclined It is poured into water, is extracted with ethyl acetate, uses anhydrous Na2SO4Dry, filter simultaneously reduced under vacuum.(used by flash chromatography Ethyl acetate:Hexamethylene (0/100)->(50/50) elute), provide the title compound of white lenticular.LCMS (methods SQD13)：460/462 (M+H), retention time 0.97min.
1H NMR(400MHz,CDCl3) ppm 8.76 (d, J=1.10Hz, 1H)；8.41 (d, J=1.1Hz, 1H)； 8.22 (d, J=7.70Hz, 1H)；7.73 (d, J=7.70Hz, 1H)；4.02 (dd, J=17.8,7.5Hz, 1H)；3.44-3.60 (m,1H)；3.35 (dd, J=17.8,7.5Hz, 1H)；2.74 (s, 3H) 1.51ppm (d, J=7.0Hz, 3H).
Example P3：2- [4- ethylsulfonyls -6- (trifluoromethyl) pyridazine -3- bases] -3- methyl -6- (trifluoromethyl) miaow Azoles simultaneously [4,5-b] pyridine (A1.014-B1.058).
Step A：5- Ethylsulfanyls -3- (trifluoromethyl) -1H- pyridazine -6- ketone.
By EtSNa (100mg, 1.2mmol) added to 5- bromo- 3- (trifluoromethyl) -1H- pyridazine -6- ketone (243mg, 1mmol, as prepared in WO 2008128995) in solution in 10ml DMF.After addition, by the mixture in room Temperature stirring 2 hours.Then the mixture is poured onto in water and is extracted with ethyl acetate three times.By the organic layer sulfuric acid of merging Sodium is dried, and is filtered and is concentrated under reduced pressure.The residue is purified by silica gel column chromatography, to provide 5- ethyl sulfanes Base -3- (trifluoromethyl) -1H- pyridazine -6- ketone (182mg, 81%).1H NMR(300Mz,DMSO-d6):δ:1.27(t,3H), 3.00(q,2H),7.38(s,1H),13.63(s,1H)；19F NMR(400MHz,DMSO-d6):δ-65.49(s,3F)；ESI- MS:223(M-H)-。
Step B：Chloro- 4- Ethylsulfanyls -6- (trifluoromethyl) pyridazines of 3-.
By 5- Ethylsulfanyls -3- (trifluoromethyl) -1H- pyridazine -6- ketone (5.8g, 26mmol) in 25ml POCl3In Mixture backflow 16h.Then, the reactant mixture is cooled to room temperature, and distills POCl under reduced pressure3.By the residue Pour into water and adjusted with sodium hydroxide to alkalescence.Gained mixture is extracted with ethyl acetate three times.By the organic of merging Layer is dried with sodium sulphate, is filtered and is concentrated under reduced pressure.Crude product is purified by silica gel column chromatography, to provide the chloro- 4- second of 3- Base sulfanyl -6- (trifluoromethyl) pyridazine (4.9g, 79%).1H NMR(300Mz,DMSO-d6):δ1.31(t,3H),3.23(q, 2H),8.00(s,1H)；1F NMR(300Mz,DMSO-d6):δ-65.19(s,3F)；ESI-MS(+):243(M+H)+。
Step C：4- Ethylsulfanyls -6- (trifluoromethyl) pyridazine -3- methyl formates.
CO gas is introduced into chloro- 4- Ethylsulfanyls -6- (trifluoromethyl) pyridazines (2.5g, 10mmol) of 3-, Pd (OAc)2(232mg, 0.1mmol), dppf (572mg, 0.1mmol) and Et3N (3.1g, 30mmol) is mixed in 30ml MeOH In compound, and interior pressure is increased into 1.5MPa.Then, the reaction is stirred into 16h at 80 DEG C.The reactant mixture is cooled down Concentrate to room temperature and under reduced pressure.The residue is purified by silica gel column chromatography, to provide 4- Ethylsulfanyls -6- (trifluoromethyl) pyridazine -3- methyl formates (1.0g, 37%).1H NMR(300Mz,DMSO-d6):δ1.28(t,3H),3.19(q, 2H),3.99(s,3H),8.01(s,1H)；19F NMR(300Mz,DMSO-d6):δ-65.61(s,3F)；ESI-MS(+):267(M +H)+,289(M+Na)+。
Step D：4- Ethylsulfanyls -6- (trifluoromethyl) Pyridazine 3 carboxylic acid.
By 4- Ethylsulfanyls -6- (trifluoromethyl) pyridazine -3- methyl formates (532mg, 2mmol) and LiOH (96mg, 4mmol) in 30ml THF and 6ml H230min is stirred at room temperature in mixture in O.Then the mixture is poured into water In, and pH is adjusted to 3-4 with watery hydrochloric acid.Gained mixture is extracted with ethyl acetate three times.By the organic layer sulphur of merging Sour sodium is dried, and is filtered and is simultaneously concentrated under reduced pressure, with obtain 4- Ethylsulfanyls -6- (trifluoromethyl) Pyridazine 3 carboxylic acid (398mg, 79%).1H NMR(300Mz,DMSO-d6):δ1.22(t,3H),3.16(q,2H),8.03(s,1H)；19F NMR(300Mz, DMSO-d6):δ-65.52(s,3F)；ESI-MS(-):267(M-H)-。
Step E：4- Ethylsulfanyls-N- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] -6- (fluoroforms Base) pyridazine -3- formamides.
By 4- Ethylsulfanyls -6- (trifluoromethyl) Pyridazine 3 carboxylic acid (230mg, 0.9mmol), N2- methyl -5- (trifluoros Methyl) pyridine -2,3- diamines (209mg, 1.1mmol, as prepared in WO 2012092051), HATU (520mg, 1.4mmol), 16h is stirred at room temperature in mixtures of the DIPEA (235mg, 1.8mmol) in 20ml DMF.Then this is mixed Thing is poured onto in water and is extracted with ethyl acetate three times.The organic layer of merging is dried with sodium sulphate, filtered and dense under vacuo Contracting.The residue is purified by silica gel column chromatography, to provide 4- Ethylsulfanyls-N- [2- (methylamino) -5- (three Methyl fluoride) -3- pyridine radicals] -6- (trifluoromethyl) pyridazine -3- formamides (369mg, 95%).1H NMR(300Mz,DMSO-d6): δ1.30(t,3H),2.87(d,3H),3.12(q,2H),7.03(s,1H),7.77(s,1H),8.07(s,1H),8.33(s, 1H),10.54(s,1H)；19F NMR(300Mz,DMSO-d6):δ:-65.43(s,3F),-58.81(s,3F)；ESI-MS(+): 426(M+H)+。
Step D：2- [4- Ethylsulfanyls -6- (trifluoromethyl) pyridazine -3- bases] -3- methyl -6- (trifluoromethyl) imidazoles And [4,5-b] pyridine (compound A1.014-B1.050)：
By the 4- Ethylsulfanyls-N- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] in 10ml AcOH - 6- (trifluoromethyl) pyridazine -3- formamides (369mg, 0.9mmol) flow back 2 hours.Then by the reactant mixture under vacuo Concentration.By the residue by silica gel flash column chromatography, with provide 2- [4- Ethylsulfanyls -6- (trifluoromethyl) pyridazine - 3- yls] -3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine (compound A1.014-B1.050,181mg, 51%).1H NMR(300Mz,DMSO-d6):δ1.27(t,3H),3.20(q,2H),4.07(s,1H),8.12(s,1H).8.75(s,1H), 8.93(s,1H)；19F NMR(300Mz,DMSO-d6):δ-66.44(s,3F),-58.33(s,3F)；ESI-MS(+):408(M+ H)+.)+.Mpt.149℃-156℃.LCMS (SQD13) Rt.1.12min, 408 (M+H).
Step E：2- [4- ethylsulfonyls -6- (trifluoromethyl) pyridazine -3- bases] -3- methyl -6- (trifluoromethyl) imidazoles And [4,5-b] pyridine (A1.014-B1.058)：
By 2- [4- Ethylsulfanyls -6- (trifluoromethyl) pyridazine -3- bases] -3- methyl -6- (trifluoromethyl) imidazo [4, 5-b] pyridine (109mg, 0.3mmol) and m-CPBA (232mg, 1.3mmol) be in 20ml CH2Cl2In mixture at room temperature Stir 2h.Then the mixture is washed with saturated sodium sulfite, aqueous sodium bicarbonate, and dried with sodium sulphate.In filtering Afterwards, the solvent is concentrated under reduced pressure.By the residue by silica gel flash chromatography, to obtain title compound (chemical combination Thing A1.014-B1.058) (113mg, 96%).1HNMR(300Mz,DMSO-d6):δ1.26(t,3H),3.91(s,3H),3.94 (q,2H),8.77(s,1H),8.79(s,1H),8.97(s,1H)；19F-NMR(300Mz,DMSO-d6):δ-65.30(s,3F),- 58.32(s,3F)；ESI-MS(+):440(M+H)+.)Mpt.172℃-174℃.LCMS (ZCQ13) Rt.1.06min, 440 (M+ H)。
Example P4：5- ethylsulfonyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] thiophene Azoles (V13.05)：
Step A 5- Ethylsulfanyl 4-thiazolecarboxylic acid ethyl esters：
At -40 DEG C, solution of the isocyanide ethyl acetate (5.6g, 0.05mol) in 100ml THF is added dropwise to uncle In suspension of the butanol potassium (6.1g, 0.055mol) in 20ml THF.After the addition, the mixture is cooled to -60 DEG C, While keeping the temperature at below -50 DEG C, carbon disulfide (3.8g, 0.05mol) is added dropwise.Then, by the mixture It is heated up to 10 DEG C and adds bromoethane (5.4g, 0.05mol).The mixture is further stirred for 2h and is concentrated under vacuum.Should Residue is purified by silica gel column chromatography, to obtain compound 5- Ethylsulfanyl 4-thiazolecarboxylic acids ethyl ester (5.6g, 52%).1H NMR(300MHz,DMSO-d6):δ1.27-1.37(m,6H),3.03(q,2H),4.25(q,2H),8.97(s,1H)；ESI- MS(+):218(M+H)+,240(M+Na)+。
Step B：5- Ethylsulfanyl thiazole -4-carboxylic acids。
5- Ethylsulfanyl 4-thiazolecarboxylic acid ethyl esters (4.6g, 0.02mol) and NaOH (1.68mg, 0.04mol) are existed Mixture in 25ml water and 50ml THF is stirred at room temperature overnight.Then, the reactant mixture is poured into watery hydrochloric acid. Then, the sediment of accumulation is filtered, is washed with water, is dried under reduced pressure, to obtain title compound (3.9g, 90%).1H NMR(300MHz,DMSO-d6):δ1.32(t,3H),3.00(q,2H),8.94(s,1H),12.94(br s,1H)；ESI-MS (+):190(M+H)+,212(M+Na)+；HPLC：99.9%.
Step C：N- [4- amino -6- (trifluoromethyl) -3- pyridine radicals] t-butyl carbamate：
To 6- (trifluoromethyl) pyridines -3,4- diamines (3.14g, 17.73mmol, as prepared in U.S.7767687) Tertbutyloxycarbonyl tert-butyl carbonate (4.64g, 21.27mmol) is added in solution in THF (50ml), and by the mixture It is stirred at 50 DEG C.After 8 hours, 1.1g (5.0mmol) tertbutyloxycarbonyl tert-butyl carbonate is added in addition, and is continued It is stirred at 50 DEG C 4 hours.Then the reactant mixture is concentrated under vacuum, and brown residue is suspended in dichloromethane In alkane, filter and be dried under vacuum, to provide the title compound of white lenticular.LCMS (method SQD13)：During reservation Between 0.79min, 278 (M+H).
Step D：N- [4- amino -6- (trifluoromethyl) -3- pyridine radicals]-N- Methyl-carbamic acid tert-butyl esters
At 20 DEG C -25 DEG C, a period through 20min, to sodium hydride (0.648g, 14.85mmol) in 30ml The N- [4- amino -6- (trifluoromethyl) -3- pyridine radicals] being dissolved in 20ml DMF is added dropwise in stirred suspension in DMF T-butyl carbamate (3.92g, 14.14mmol).It is stirred at room temperature after 15min, addition iodomethane (2.21g, 15.55mmol).At ambient temperature after 30min, it is waterborne that the mixture is poured onto 200ml, is extracted with ethyl acetate two It is secondary, and by the organic component priority water and salt water washing of merging, use Na2SO4Dry and be concentrated under vacuum.From ethyl acetate/ Crude product is recrystallized in heptane, to provide the title compound of white lenticular (3.18g).LCMS (method SQD13)：Retain Time 0.85min, 292 (M+H).
Step E：N3- methyl -6- (trifluoromethyl) pyridine -3,4- diamines：
To N- [4- amino -6- (trifluoromethyl) -3- pyridine radicals]-N- Methyl-carbamic acids tert-butyl ester (3.53g, 12.119mmol) in the limpid colourless solution in Yu dioxanes add hydrogen chloride (2M solution of the 18ml in water, 36.36mmol), and by the mixture it is heated to flowing back.After gas release stops, the reactant mixture is cooled to room Temperature, and handled with solid sodium bicarbonate (3.1g, 36.9mmol).The slurry is diluted with water and is extracted with ethyl acetate twice. By the organic layer priority water and salt water washing of merging, Na is used2SO4Dry and be concentrated under vacuum, to provide 2.25g in colourless The title compound of lenticular, Mpt, 138 DEG C -140 DEG C；LCMS (method SQD13)：, residence time 0.24min, 192 (M+H).
Alternately,N3- methyl -6- (trifluoromethyl) pyridine -3,4- diaminesIt can be obtained by following procedure：
To 6- (trifluoromethyl) pyridine -3,4- diamines (2.0g, 12.2mmol) and potassium carbonate (3.2g, 23.1mmol) in second Iodomethane (0.8mL) is added in solution in nitrile (10mL).The reactant mixture is stirred overnight at 30 DEG C.Filter out carbonic acid Potassium；Filtrate is dried under vacuum and purifies (oil with silica gel column chromatography:EtOAc=4:3) it is in, faint yellow solid shape to obtain Title compound (0.32g, yield：37%).1H NMR(400MHz,DMSO-d6):δ(ppm)7.57(s,1H),6.83(s, 1H), 5.82 (s, 2H), 5.23 (d, J=4.8Hz, 1H), 2.80 (d, J=4.8Hz, 3H).19F NMR(300MHz,DMSO- d6):δ(ppm)-60.12(s,3F)。ESI-MS(+):192(M+H)。
Step F：5- Ethylsulfanyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] thiazole (compound A6.002-B7.037)：
By 5- Ethylsulfanyls thiazole -4-carboxylic acid (567mg, 3mmol), N3- methyl -6- (trifluoromethyl) pyridine -3,4- Diamines (483mg, 3mmol) and N- (3- dimethylaminopropyls)-N '-ethylcarbodimide hydrochloride (EDC.HCL) The mixture backflow 16h of (576mg, 3.6mmol) in 20ml pyridines.By the reactant mixture reduced under vacuum and pass through silica gel Column chromatography purifies, to provide title compound (120mg), 5- Ethylsulfanyls-N- [5- (methylamino) -2- (trifluoromethyl) - 4- pyridine radicals] thiazole -4-carboxamide (51mg) and N- [4- amino -6- (trifluoromethyl) -3- pyridine radicals] -5- ethyl sulfanes Base-N- methYl-thiazol -4- formamides (162mg).Latter two compound is dissolved in 10ml AcOH and the 16h that flows back.Then The mixture is concentrated under vacuum, and the residue is purified by silica gel column chromatography, to provide other title compound (140mg)。1H NMR(400MHz,DMSO-d6):δ1.34(t,3H),3.08(q,2H),4.23(s,3H),8.20(s,1H), 9.17(s,1H),9.27(s,1H)；19F-NMR(400MHz,DMSO-d6):δ-59.68(s,3F)；ESI-MS：345(M+H)+, 367(M+Na)+；Mpt.167℃-169℃.
Step G：5- ethylsulfonyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] thiazole (V13.05)
By 5- Ethylsulfanyls -4- [3- methyl -6- (trifluoromethyl) imidazos [4,5-c] in 10ml dichloromethane Pyridine -2- bases] 0.5h is stirred at room temperature in thiazole (140mg, 0.4mmol) and m-CPBA (280mg, 1.6mmol).Then should Mixture pours into Na2CO3And Na2SO3In saturated solution in water, and it is extracted with ethyl acetate three times.By the organic of merging Layer is dried with sodium sulphate, is filtered and is concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide title compound Thing (147mg, 96%).1H NMR(400MHz,DMSO-d6):δ1.28(t,3H),4.04(q,2H),4.05(s,3H),8.32 (s,1H),9.29(s,1H),9.70(s,1H)；19F-NMR(400MHz,DMSO-d6):δ-58.84(s,3F)；ESI-MS(+): 377(M+H)+,399(M+Na)+；LCMS (method SQD13) Rt.0.85min 377 (M+H).Mpt.178℃-179℃
Example P5：2- [5- (difluoro-methoxy) -3- ethylsulfonyl -2- pyridine radicals] -3- methyl -6- (trifluoromethyl) Imidazo [4,5-c] pyridine (compound V12.19)：
Step A：Bis- chloro- 5- of 2,3- [(4- methoxyphenyls) methoxyl group] pyridine
By 5,6- dichloropyridine -3- alcohol (8.2g, 50mmol), 4- methoxy-benzyls chlorine (11.8g, 75mmol) and K2CO3 (21.0g, 150mmol) is in CH3Mixture backflow 6h in CN (250ml).Then, the mixture is cooled to room temperature and mistake Filter.Filtrate is concentrated under reduced pressure and purifies the residue by silica gel column chromatography, to provide the title of white solid-like Compound (10.0g, 70% yield).1H NMR(400MHz,DMSO-d6):δ3.72(s,3H),5.09(s,2H),6.92(d,J =8.8Hz, 2H), 7.35 (d, J=8.8Hz, 2H), 7.89 (d, J=2.8Hz, 1H), 8.15 (d, J=2.8Hz, 1H)；ESI- MS(+):284(M+H)+；Mpt.:124℃-125℃.
Step B：The chloro- 5- of 3- [(4- methoxyphenyls) methoxyl group] pyridine -2- Ethyl formates
By CO gases introduce 2,3- bis- chloro- 5- [(4- methoxyphenyls) methoxyl group] pyridine (10.0g, 35.2mmol), Dppf (975mg, 1.8mmol), Pd (OAc)2(158mg, 0.7mmol) and Et3N (10.2ml, 70.4mmol) is in 110ml EtOH In mixture in, and interior pressure increases to 1.6MPa.By the reactant mixture in 125 DEG C of stir abouts 7 hours.Then, will The mixture is cooled to room temperature and filtered.Filtrate is concentrated under reduced pressure and purifies the residue by silica gel column chromatography, with Obtain the title compound (6.8g, 60% yield) in faint yellow solid shape.1H NMR(400MHz,DMSO-d6):δ1.26(t,J =6.8Hz, 3H), 3.72 (s, 3H), 4.28 (q, J=6.8Hz, 2H), 5.15 (s, 2H), 6.92 (d, J=8.0Hz, 2H), 7.37 (d, J=8.0Hz, 2H), 7.76 (d, J=2.0Hz, 1H), 8.32 (d, J=2.0Hz, 1H)；ESI-MS(+):322(M+ H)+,345(M+Na)+；Mp:45℃-46℃.
Step C：3- Ethylsulfanyls -5- [(4- methoxyphenyls) methoxyl group] pyridine -2- Ethyl formates
By the chloro- 5- of 3- [(4- methoxyphenyls) methoxyl group] pyridine -2- Ethyl formates (6.4g, 0.02mol) and EtSNa The mixture of (3.35g, 0.04mol) in 50ml DMF stirs 4h at 90 DEG C.Then the mixture is poured onto in water and be used in combination Ethyl acetate extracts three times.The organic layer of merging is dried with sodium sulphate, filters and concentrates under reduced pressure.The residue is passed through Silica gel column chromatography purifies, to provide title compound (3g, 43% yield).1H NMR(400MHz,DMSO-d6):δ1.22(t, 3H),1.29(t,3H),2.97(q,2H),3.76(s,3H),4.27(q,2H),5.24(s,2H),6.96(d,2H),7.34(d, 1H),7.41(d,2H),8.15(d,1H)；ESI-MS(+):370(M+Na)+。
Step D：3- Ethylsulfanyls -5- [(4- methoxyphenyls) methoxyl group] pyridine-2-carboxylic acids：
By ethyl -3- Ethylsulfanyls -5- [(4- methoxyphenyls) methoxyl group] pyridine -2- formic acid esters (3g, 0.009mol) it is stirred at room temperature overnight with mixtures of the NaOH (692mg, 0.017mol) in 10ml water and 30ml THF. Then, the reactant mixture is poured into watery hydrochloric acid, and be extracted with ethyl acetate three times.By the organic layer sodium sulphate of merging Dry, filter and be concentrated under vacuum.By the residue by silica gel flash column chromatography, to provide title compound (2.3g, 83% yield).1H NMR(400MHz,DMSO-d6):δ1.23(t,3H),2.94(q,2H),3.76(s,3H),5.24 (s,2H),6.96(d,2H),7.32(d,1H),7.41(d,2H),8.13(d,1H),12.69(br s,1H)；ESI-MS(+): 320(M+H)+,342(M+Na)+。
Step E：3- Ethylsulfanyls -5- [(4- methoxyphenyls) methoxyl group]-N- [5- (methylamino) -2- (fluoroforms Base) -4- pyridine radicals] pyridine-2-carboxamide：
By compound 3- Ethylsulfanyls -5- [(4- methoxyphenyls) methoxyl group] pyridine-2-carboxylic acids (284mg, 0.89mmol), N3- methyl -6- (trifluoromethyl) pyridines -3,4- diamines (149mg, 0.89mmol, such as in example P4 steps E Prepare) and mixtures of the EDC.HCl (188mg, 0.98mmol) in 10ml pyridines flow back 16h.Then, the mixture is existed Reduced under vacuum, it is diluted with water and is extracted with ethyl acetate.By the organic layer Na of merging2SO4Dry, concentrate under reduced pressure, with Thick title product (320mg) is provided, it is directly used in next step without further purification.
Step F：5- Ethylsulfanyls -6- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] pyridine - 3- alcohol：
By 3- Ethylsulfanyls -5- [(4- methoxyphenyls) methoxyl group]-N- [5- (methyl ammonia in 10ml AcOH Base) -2- (trifluoromethyl) -4- pyridine radicals] pyridine-2-carboxamide (320mg) backflow 16h.Then by the mixture under vacuo Concentration, and the residue is purified by silica gel column chromatography, to provide title compound (151mg).1H-NMR(400MHz, DMSO-d6):δ1.18(t,3H),2.91(q,2H),3.96(s,3H),7.34(d,1H),8.11(d,1H),8.22(s,1H), 9.18(s,1H),10.74(s,1H)；19F-NMR(400MHz,DMSO-d6):δ-64.84(s,3F)；ESI-MS(+):355(M+ H)+。
Step G：2- [5- (difluoro-methoxy) -3- Ethylsulfanyl -2- pyridine radicals] -3- methyl -6- (trifluoromethyl) miaow Azoles simultaneously [4,5-c] pyridine：
At 50 DEG C, by CHClF2Gas introducing 5- Ethylsulfanyls -6- [3- methyl -6- (trifluoromethyl) imidazo [4, 5-c] pyridine -2- bases] pyridine -3- alcohol (100mg, 0.28mmol) and Cs2CO3(460mg, 1.41mmol) is in 10ml DMF Continue 2 hours in mixture.Then the mixture is poured onto in water and is extracted with ethyl acetate three times.By the organic layer of merging Dried with sodium sulphate, filter and be concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide title product (94mg, 82%).1H NMR(400MHz,DMSO-d6):δ1.35(t,3H),2.93(q,2H),4.07(s,3H),6.67(t, 1H),7.52(d,1H),8.19(s,1H),8.36(d,1H),8.95(s,1H)；19F-NMR(400MHz,DMSO-d6):δ- 81.81(d,1F),-66.25(s,3F)；ESI-MS(+):405(M+H)+,427(M+Na)+,459(M+MeOH+Na)+；HPLC: 98.2%
Step H：2- [5- (difluoro-methoxy) -3- ethylsulfonyl -2- pyridine radicals] -3- methyl -6- (trifluoromethyl) miaow Azoles simultaneously [4,5-c] pyridine (compound V12.19)：
By 2- [5- (difluoro-methoxy) -3- Ethylsulfanyl -2- pyridine radicals] -3- methyl -6- in 5ml dichloromethane (trifluoromethyl) imidazo [4,5-c] pyridine (80mg, 0.2mmol) and m-CPBA (136mg, 0.8mmol) are stirred at room temperature 0.5h.Then the mixture is poured into Na2CO3And Na2SO3Saturated aqueous solution in, and be extracted with ethyl acetate three times.Will The organic layer of merging is dried with sodium sulphate, is filtered and is concentrated under vacuum.The residue is purified by silica gel column chromatography, with to Go out title compound (67mg, 88%).1H NMR(400MHz,DMSO-d6):δ1.19(m,3H),3.78(d,3H),3.90(s, 3H),6.77(t,1H),8.11(s,2H),8.30(d,1H),8.86(d,1H),9.00(s,1H)；19F-NMR(400MHz, DMSO-d6):δ-78.62(d,1F),-62.07(s,3F)；ESI-MS(+):437(M+H)+.Mpt.146℃-148℃；LCMS (method SQD13)：Retention time 1.03 minutes, 405 (M+H).
Example P6：6- (2- ethanesulfonyl -6- trifluoromethylpyridin -3- bases) -3- Methyl-2-trifluoromethyls -3,5- Dihydro-diimidazole simultaneously [4,5-b；4 ', 5 '-e] pyridine (compound V26.03)：
Step A：3- methyl -6- nitros -2- (trifluoromethyl) imidazo [4,5-b] pyridine：
At 70 DEG C, will be stirred in the N2- methyl-5-nitros in TFA (10mL)-pyridine -2,3- diamines (10g, 59.52mmol) Mix 16h.By the mixture by silicon chromatographic purifying, with obtain in yellow solid pure title compound (9.81g, 67%).1HNMR(300MHz,d6-DMSO):δ 9.46 (d, J=2.4Hz, 1H), 9.22 (d, J=2.4Hz, 1H), 4.04 (s, 3H)。
Step B：3- methyl -6- nitro -4- oxidations -2- (trifluoromethyl) imidazo [4,5-b] pyridines -4-：
To 3- methyl -6- nitros -2- (trifluoromethyl) imidazo [4,5-b] pyridines (5.3g, 21.54mmol) in dichloromethane Perhydrit (UHP, 6.17g, 65.7mmol) is added in solution in alkane dichloromethane (60mL), is cooled with an ice bath, and by Drop addition TFAA (13.6g, 65.7mmol).The mixture is stirred 18 hours at ambient temperature.TCL displays consumption is about 50% parent material.In DEG C another batch of UHP (6.08g, 64.63mmol) of addition and a TFAA (13.8g, 64.63mmol).Should Mixture is stirred for 24 hours in environment temperature.The reactant mixture is diluted with water, stirs and continues 20min.Separate organic Phase, and by aqueous phase with dichloromethane extraction (3 times).By the organic phase water and salt water washing of merging, Na is used2SO4Dry, and It is concentrated under vacuum.By the residue by silicon chromatographic purifying, to provide the title compound of white solid-like (1.91g).1HNMR(300MHz,d6-DMSO):δ 9.17 (d, J=1.8Hz, 1H), 8.83 (d, J=1.8Hz, 1H), 4.41 (d, J= 1.2Hz,3H)。
Step C：Chloro- 3- methyl -6- nitros -2- (trifluoromethyl) imidazo [4,5-b] pyridines of 5-：
By 3- methyl -6- nitro -4- oxidations -2- (trifluoromethyl) imidazo [4,5-b] pyridine -4- (2.8g, 10.69mmol) it is dissolved in POCl3In (50mL), and return stirring 2 hours.The mixture is poured into frozen water, uses EtOAc Extract (3 times).By organic phase NaHCO3(water-based) and water washing, use Na2SO4Dry, drying is evaporated to, to obtain thick title Compound (3.8g), it is used for next step without further purification.
Step D：N5,3- dimethyl -6- nitros -2- (trifluoromethyl) imidazo [4,5-b] pyridin-5-amine：
To chloro- 3- methyl -6- nitros -2- (trifluoromethyl) imidazo [4,5-b] pyridines (3.8g) of compound 5- in ethanol MeNH is added in solution in (40mL)2(water-based, 5mL).The reactant mixture is stirred 18 hours at ambient temperature.Should Mixture filters, and is dried under vacuum, to obtain the pure title compound (2.3g) of white solid-like.1HNMR (300MHz,d6-DMSO):δ 8.90 (s, 1H), 8.64-8.62 (m, 1H), 3.79 (d, J=1.2Hz, 3H), 3.07 (d, J= 4.8Hz,3H)。
Step E：N5,3- dimethyl -2- (trifluoromethyl) imidazo [4,5-b] pyridine -5,6- diamines：
In N2Under, to compound N 5,3- dimethyl -6- nitros -2- (trifluoromethyl) imidazo [4,5-b] pyridin-5-amine 200mg palladium carbons are added in the solution of (2.3g, 8.36mmol) in EtOAc (30mL) and methanol (30mL).At room temperature, use The mixture is hydrogenated 4h by hydrogen balloon.The mixture is filtered by diatomite, and filtrate is evaporated to drying.By the residue By silicon chromatographic purifying, to provide the title compound (1.6g, 78%) in violet solid shape.1HNMR(300MHz,d6- DMSO):δ 7.01 (s, 1H), 6.29 (d, J=3.3Hz, 1H), 4.69 (s, 2H), 3.77 (d, J=1.2Hz, 3H), 2.92 (d, J =4.5Hz, 3H).
Step F：The bromo- 2- of 3- chloro- 6- (trifluoromethyl) pyridine：
By compound 2- chloro- 6- (trifluoromethyl) pyridine -3- amine
(5.88g, 30mmol, as prepared in WO 2009110475), isoamyl nitrite (7.02g, 60mmol), P-TsOH (6.19g, 36mmol), TBAB (19.32g, 60mmol) and CuBr2(1.40g, 6mmol) is mixed in 60ml MeCN 4h is stirred at room temperature in compound.Then, the mixture is concentrated under vacuum and purifies the residue by silica gel column chromatography, To provide title compound (5.85g, 75%).1H-NMR(300Mz,DMSO-d6):δ7.85(d,1H),8.52(s,1H)；19F- NMR(300Mz,DMSO-d6):δ-65.72(s,3F)。
Step G：Bromo- 2- Ethylsulfanyls -6- (trifluoromethyl) pyridines of 3-：
By the bromo- 2- of 3- chloro- 6- (trifluoromethyl) pyridine (5.98g, 23mmol) and EtSNa (1.93g, 23mmol) in 50ml Mixture stirring 2h in MeCN.Then, the mixture is poured into watery hydrochloric acid, and be extracted with ethyl acetate three times.It will close And organic layer dried with sodium sulphate, filter and be concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide Title compound (4.06g, 58%).1H-NMR(300Mz,DMSO-d6):δ1.26(t,3H),3.08(q,2H),7.50(d, 1H),8.20(d,1H)；19F-NMR(300Mz,DMSO-d6):δ-65.45(s,3F)。
Step H：2- Ethylsulfanyls -6- (trifluoromethyl) Nicotinicum Acidum ethyl ester：
CO gas is introduced into bromo- 2- Ethylsulfanyls -6- (trifluoromethyl) pyridines (572mg, 2mmol) of 3-, Pd (OAc)2(90mg, 0.4mmol), dppf (444mg, 0.8mmol) and Et3N (1.01g, 10mmol) is in 10ml EtOH and 10ml In mixture in DMF, and interior pressure is increased to 2.7MPa.The mixture is heated into 6h at 90 DEG C and is cooled to room temperature.So Afterwards, it is poured into water and is extracted with ethyl acetate three times.The organic layer of merging is dried with sodium sulphate, filtered and in vacuum Lower concentration.By the residue by flash silica chromatography, to provide title compound (795mg, 88%).1H-NMR (300Mz,DMSO-d6):δ1.23(t,3H),1.28(t,3H),3.05(q,2H),4.29(q,2H),7.66(d,1H),8.39 (d,1H)；19F-NMR(300Mz,DMSO-d6):δ-62.88(s,3F)。
Step I：2- Ethylsulfanyls -6- (trifluoromethyl) pyridine-3-carboxylic acid：
By 2- Ethylsulfanyls -6- (trifluoromethyl) Nicotinicum Acidum ethyl esters (480mg, 1.7mmol) and KOH (482mg, 8.6mmol) 16h is stirred at room temperature in the mixture in 10ml water and 10ml THF.The reactant mixture is poured into dilute salt In acid and it is extracted with ethyl acetate.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.By the residue Purified by silica gel column chromatography, to provide title compound (430mg, 90%).1H-NMR(300Mz,DMSO-d6):δ1.23(t, 3H),3.02(q,2H),7.64(d,1H),8.37(d,1H),13.85(br s,1H)；19F-NMR(300Mz,DMSO-d6):δ- 62.78(s,3F)；ESI-MS(-):250(M-H)-。
Step J：2- Ethylsulfanyls-N- [3- methyl -5- (methylamino) -2- (trifluoromethyl) imidazo [4,5-b] pyrroles Pyridine -6- bases] -6- (trifluoromethyl) pyridine-3-carboxamide：
By 2- Ethylsulfanyls -6- (trifluoromethyl) pyridine-3-carboxylic acid (251mg, 1mmol), N5,3- dimethyl -2- (three Methyl fluoride) imidazo [4,5-b] pyridine -5,6- diamines (245mg, 1.0mmol, the product of the step E in this example), The mixture stirring 16h of HATU (570mg, 1.5mmol) and DIPEA (258mg, 2mmol) in 10ml DMF.By the mixture It is concentrated under vacuum, and is purified by silica gel column chromatography, provides title compound (408mg, 84%).1H NMR(300Mz, DMSO-d6):δ1.26(t,3H),2.91(d,3H),3.07(q,2H),3.83(s,3H),6.69(q,1H),7.76(d,1H), 7.80(s,1H),8.44(d,1H),9.97(s,1H)；19F NMR(300Mz,DMSO-d6):δ-62.50(s,3F),-57.02 (s,3F)。
Step K：6- (2- Ethylsulfanyl -6- trifluoromethylpyridin -3- bases) -3- Methyl-2-trifluoromethyls -3,5- two Hydrogen-diimidazole simultaneously [4,5-；4 ', 5 '-e] pyridine：
By 2- Ethylsulfanyls-N- [3- methyl -5- (methylamino) -2- (trifluoromethyl) imidazo [4,5-b] pyridine - 6- yls] mixture backflow 2h of -6- (trifluoromethyl) pyridine-3-carboxamide (382mg, 0.8mmol) in 10ml AcOH, so The mixture is concentrated under vacuum afterwards and purifies the residue by silica gel column chromatography, to provide title compound (231mg, 63%).1H-NMR(300Mz,CDCl3):δ1.33(t,3H),3.22(q,2H),3.85(s,3H),4.09(s,3H), 7.51(d,1H),7.86(d,1H),8.59(d,1H)；19F NMR(300Mz,CDCl3):δ-68.64(s,3F),-63.72(s, 3F)；ESI-MS(+):461(M+H)+,483(M+Na)+.Mpt.154℃-156℃；LCMS；Retention time 1.13 minutes, 461 (M +H)
Step L：6- (2- ethanesulfonyl -6- trifluoromethylpyridin -3- bases) -3- Methyl-2-trifluoromethyls -3,5- two Hydrogen-diimidazole simultaneously [4,5-b；4', 5'-e] pyridine (compound V26.03)：
By 6- (2- Ethylsulfanyl -6- trifluoromethylpyridin -3- bases) -3- Methyl-2-trifluoromethyl -3,5- dihydros-two Imidazo [4,5-；4 ', 5 '-e] pyridine (161mg, 0.35mmol) and m-CPBA (242mg, 1.4mmol) be in 10ml dichloromethane In mixture 2h is stirred at room temperature.Then the mixture is poured into NaHCO3And Na2SO3In saturated solution in water, And it is extracted with ethyl acetate three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.By the residue Purified by silica gel column chromatography, to provide the title compound of white solid-like (163mg, 94%).1H NMR(300Mz, CDCl3):δ1.30(t,3H),3.53(q,2H),3.85(s,3H),4.09(s,3H),8.08(d,1H),8.30(d,1H), 8.54(s,1H)；19F NMR(300Mz,CDCl3):δ-63.78(s,3F),-59.57(s,3F)；ESI-MS:493(M+H)+, 515(M+Na)+.Mpt.197℃-199℃；LCMS (method SQD13)：Retention time 0.95 minute, 493 (M+H).
Example P7：4- ethylsulfonyls -5- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] -2- (trifluoromethyl) thiazole (compound V14.05)：
Step A：4- bromo- 2- (trifluoromethyl) thiazole：
By the bromo thiazoles of 2,4- bis- (24.3g, 0.1mol), FSO2CF2COOCH3(23.0g, 0.12mmol) and CuI (19.0g, 0.1mol) mixture in 200ml DMF heats 4 hours at 100 DEG C.Then, the reactant mixture is poured into water, and The title compound (22.9g, 83%) is distilled under water-aspirator pressure.The product is used in next step without further purification Suddenly.
Step B：4- bromo- 2- (trifluoromethyl) thiazole-5-carboxylic acid：
At 60 DEG C, under nitrogen atmosphere, n-BuLi (2.5M in hexane, 62mmol) is added slowly to anhydrous in 150ml I-Pr in THF2In NH (6g, 59mmol).After the addition, the mixture is stirred for 0.5 hour at the same temperature.So Afterwards, 4- bromo- 2- (trifluoromethyl) thiazole (12g, 52.0mmol) is slowly added into thing mixed above, and continues to stir 20min. The mixture is poured into dry ice, and is stirred for one hour.The reactant mixture is allowed to be warming up to environment temperature, with acetic acid second Ester is diluted, and organic phase is successively washed with water and saturated brine, is dried with sodium sulphate, is filtered and be dried under vacuum, with to Go out title product (10.1g, 71%).
Step C：4- bromo- 2- (trifluoromethyl) thiazole -5- phosgenes：
By 4- bromo- 2- (trifluoromethyl) thiazole-5-carboxylic acids (276mg, 1mmol) in 10ml SOCl2In mixture backflow 4 hours.Distill excessive SOCl2, to provide thick title product (295mg), it is directly used in down without further purification One step.
Step D：The bromo- 5- of 4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] -2- (trifluoromethyl) Thiazole：
By 4- bromo- 2- (trifluoromethyl) thiazole -5- phosgenes (477mg, 1.7mmol) and N3- methyl -6- (trifluoromethyl) Mixture backflow of pyridine -3, the 4- diamines (330mg, 1.7mmol, as prepared in example P4 steps E) in 10ml toluene 16h.Then the reactant mixture is concentrated under vacuum, and the residue is purified by silica gel column chromatography, to provide title Compound (358mg, 44%).1H NMR(300Mz,DMSO-d6):δ:3.98(s,3H),8.30(s,1H),9.28(s,1H)；19F NMR(300Mz,DMSO-d6):δ-61.58(s,3F),-57.88(s,3F)；ESI-MS:433(M+H)+。
Step E：4- Ethylsulfanyls -5- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] -2- (trifluoromethyl) thiazole：
EtSNa (123mg, 1.5mmol) is added to the bromo- 5- of 4- [3- methyl -6- (trifluoromethyl) imidazos [4,5-c] Pyridine -2- bases] in mixture of -2- (trifluoromethyl) thiazole (315mg, 0.7mmol) in 10ml DMF., will after addition The mixture is stirred at room temperature 2 hours.Then the mixture is poured onto in water and is extracted with ethyl acetate three times.By merging Organic layer is dried with sodium sulphate, is filtered and is concentrated under reduced pressure.Crude product is purified by silica gel column chromatography, it is titled to provide Compound (176mg, 58%).1H NMR(300Mz,DMSO-d6):δ1.25(t,3H),3.18(q,2H),4.02(s,3H),8.25 (s,1H),9.24(s,1H)；19F NMR(300Mz,DMSO-d6):δ-59.80(s,3F),-55.95(s,3F)；ESI-MS:413 (M+H)+.LCMS (method SQD13)：Rt.1.12 minutes, 413 Mpt.92 DEG C -94 DEG C of (M+H)
Step F：4- ethylsulfonyls -5- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] -2- (trifluoromethyl) thiazole (compound V14.05)：
By 4- Ethylsulfanyls -5- [3- methyl -6- (trifluoromethyl) imidazo [4,5-c] pyridine -2- bases] -2- (trifluoros Methyl) thiazole (109mg, 0.3mmol) and m-CPBA (228mg, 1.3mmol) be in 15ml CH2Cl2In mixture stirred in room temperature Mix 2h.The reactant mixture saturated sodium sulfite and aqueous sodium bicarbonate are diluted, and separate organic layer, is done with sodium sulphate It is dry, filter and be concentrated under vacuum.By the residue by flash silica chromatography, with provide title compound (71mg, 61%).1H NMR(300Mz,DMSO-d6):δ1.16(t,3H),3.51(q,2H),3.89(s,3H),8.28(s,1H),9.27 (s,1H)；19F NMR(300Mz,DMSO-d6):δ-59.81(s,3F),-55.74(s,3F)；ESI-MS:445(M+H)+,467 (M+Na)+,499(M+MeOH+Na)+。
Example P8：4- ethylsulfonyls -2- (trifluoromethyl) -5- [7- (trifluoromethyl) imidazo [1,2-a] pyridine -2- Base] thiazole (compound V2.11)：
Step A：Bromo- N- methoxy-. N-methyls -2- (trifluoromethyl) thiazole -5- formamides of 4-：
By 4- bromo- 2- (trifluoromethyl) thiazole-5-carboxylic acid
(5.8g, 21mmol, as prepared described in example P7 steps B), N, O- dimethyl hydroxylamines hydrochloride (2.5g, 25mmol), the mixture of HATU (9.6g, 25mmol) and DIPEA (5.4g, 42mmol) in 35ml DMF stirs at room temperature Mix 16h.The mixture is poured into water and is extracted with ethyl acetate three times.The organic layer of merging is dried with sodium sulphate, mistake Filter and be concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide title compound (4.7g, 70%).1H NMR(300Mz,DMSO-d6):δ3.27(s,3H),3.68(s,3H)；19F NMR(300Mz,DMSO-d6):δ-56.33(s, 3F)；ESI-MS:341(M+Na)+。
Step B：1- [4- bromo- 2- (trifluoromethyl) thiazole -5- bases] ethyl ketone：
At 0 DEG C, under nitrogen atmosphere, MeMgBr (3M is in middle THF, 15ml, 45mmol) is added dropwise to the bromo- N- methoxies of 4- In solution of base-N- methyl -2- (trifluoromethyl) thiazole -5- formamides (5.7g, 21mmol) in 30ml dry THFs.Adding In addition after, it is allowed to which the mixture is heated up to environment temperature and stirs 30min.Then the mixture is poured into watery hydrochloric acid and be used in combination Ethyl acetate extracts three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.The residue passes through fast Fast purified on silica, to provide title product (4.8g, 86%).1H NMR(300Mz,DMSO-d6):δ2.68(s,3H)；19F NMR(300Mz,DMSO-d6):δ-66.14(s,3F)。
Step C：4- bromo- 2- (trifluoromethyl) -5- [7- (trifluoromethyl) imidazo [1,2-a] pyridine -2- bases] thiazole：
At 120 DEG C, under air atmosphere, by 1- [4- bromo- 2- (trifluoromethyl) thiazole -5- bases] ethyl ketone (220mg, 1mmol), 2- amino -4- (trifluoromethyl) pyridine (193mg, 1.2mmol, as prepared in WO2011090122), Cu (OAc)2.H2O (12mg, 0.1mmol), 1,10- phenanthrolenes (18mg, 0.1mmol), ZnI2(32mg, 0.1mmol) in Mixture stirring 16h in 12ml dichloro-benzenes.The mixture is concentrated under vacuum, and the residue is passed through into silica gel column chromatography Purifying, to provide title compound (153mg, 36%).1H NMR(300Mz,DMSO-d6):δ7.25(d,1H),8.12(s, 1H),8.84(d,1H),8.96(s,1H)；19F NMR(300Mz,DMSO-d6):δ-64.34(s,3F),-62.89(s,3F)； ESI-MS(-):414(M-H)-；HPLC：97.7%.
Step D：4- Ethylsulfanyls -2- (trifluoromethyl) -5- [7- (trifluoromethyl) imidazo [1,2-a] pyridine -2- Base] thiazole：
EtSNa (157mg, 1.9mmol) is added to 4- bromo- 2- (trifluoromethyl) -5- [7- (trifluoromethyl) imidazos [1,2-a] pyridine -2- bases] in mixture of the thiazole (389mg, 0.9mmol) in 15ml DMF.After the addition, this is mixed Compound stirs 2 hours at ambient temperature.Then the reactant mixture is poured into water and is extracted with ethyl acetate three times.Will The organic layer of merging is dried with sodium sulphate, is filtered and is concentrated under vacuum.The residue is purified by silica gel column chromatography, with to Go out title compound (281mg, 76%).1H NMR(300Mz,DMSO-d6):δ1.28(t,3H),3.23(q,2H),7.24(d, 1H),8.11(s,1H),8.75(s,1H),8.86(d,1H)；19F NMR(300Mz,DMSO-d6):δ-66.81(s,3F),- 65.09(s,3F)；ESI-MS(+):398(M+H)+；HPLC:96.3%.
Step E：4- ethylsulfonyls -2- (trifluoromethyl) -5- [7- (trifluoromethyl) imidazo [1,2-a] pyridine -2- Base] thiazole(compound V2.11)：
By 4- Ethylsulfanyls -2- (trifluoromethyl) -5- [7- (trifluoromethyl) imidazo [1,2-a] pyridine -2- bases] thiophene Azoles (80mg, 0.2mmol) and m-CPBA (105mg, 0.6mmol) are in 10ml CH2Cl2In mixture environment temperature stir 2 Hour.Then the mixture is washed with saturated sodium sulfite and aqueous sodium bicarbonate.Organic layer is dried with sodium sulphate, filtered And it is concentrated under vacuum.By the residue by flash silica chromatography, to provide title compound (66mg, 77%).1H NMR(300Mz,DMSO-d6):δ1.22(t,3H),3.57(q,2H),7.27(d,1H),8.16(s,1H),8.94(d,2H)；19F NMR(300Mz,DMSO-d6):δ-48.60(s,3F),-50.52(s,3F)；ESI-MS(+):430(M+H)+；HPLC:96.9%. Mpt.126℃-128℃
Example P9：3- methyl -2- [3- methyl sulphonyls -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) imidazoles And [4,5-c] pyridine (compound V12.18)：
Step A：3- methyl sulphonyls -5- (trifluoromethyl) pyridine -2- phosgenes：
By 3- methyl sulphonyls -5- (trifluoromethyl) pyridine-2-carboxylic acids (1.0g, 3.7mmol, such as in US20100234603 Middle preparation) it is suspended in SOCl2In (5mL), 1 drop DMF is added into the mixture.The reactant mixture is heated to flowing back, And stir 3h.Then be evaporated to drying under reduced pressure, with provide the title compound of white solid-like (1.1g, 100%).The residue is directly used in next step without further purification.
Step B：N- [5- (methylamino) -2- (trifluoromethyl) -4- pyridine radicals] -3- methyl sulphonyl -5- (fluoroforms Base) pyridine-2-carboxamide：
It is molten in 5ml toluene to 3- methyl sulphonyls -5- (trifluoromethyl) pyridine -2- phosgenes (80mg, 0.3mmol) Compound N 3- methyl -6- (trifluoromethyl) pyridines -3,4- diamines (60mg, 1.1mmol, such as in example P4 steps E are added in liquid Middle preparation), the reactant mixture is then heated up to 100 DEG C and continues 5 hours.After this, room temperature is cooled to be used in combination 15ml water dilutes, and with EtOAc extractions three times.The organic layer of merging is dried with sodium sulphate, and purified by silica gel column chromatography (EtOAc:Petroleum ether=1/4), to provide the title compound of white solid-like (50mg, 40% yield).
Step C：3- methyl -2- [3- methyl sulphonyls -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) imidazoles And [4,5-c] pyridine (compound V12.18)：
5- methyl-N- [2- methyl -5- (methylamino) -4- pyridine radicals] -3- methyl sulphonyls-pyridine-2-carboxamide (85mg, 0.2mmol) is added to 5ml acetic acid, and reactant mixture is heated up into 100 DEG C of lasting 12h.By the reactant mixture It is cooled to room temperature and is diluted with 20ml water, and with EtOAc extractions three times.The organic layer of merging is done with sodium sulphate It is dry, and (EtOAc is purified by silica gel column chromatography:Petroleum ether=1/4), to provide the title compound of white solid-like (40mg, 50% yield).1H NMR(300MHz,CDCl3)δ3.65(s,3H),3.94(s,3H),8.11(s,1H),8.82(s, 1H),9.01(s,1H),9.24(s,1H)。19F NMR(300Mz,CDCl3)δ-67.27(s,3H),δ-63.34(s,3H)。ESI- MS:425(M+1).Mpt..234℃-236℃.LCMS (method SQD 13) Rt.0.93 minutes, 425 (M+H).
Example P10：2- [2- ethylsulfonyls -6- (trifluoromethyl) -3- pyridine radicals] -7- (trifluoromethyl) imidazo [1, 2-a] pyridine (compound V3.05)：
Step A：2- Ethylsulfanyls -6- (trifluoromethyl) pyridine -3- phosgenes：
By 2- Ethylsulfanyls -6- (trifluoromethyl) pyridine-3-carboxylic acid
(502mg, 2mmol, as prepared in example P6 steps I) is in 10ml SOCl2In mixture flow back 4 hours. Then, excessive SOCl is evaporated2, to provide title compound (538mg, 100%), it is directly used in without further purification Next step.
Step B：2- Ethylsulfanyl-N- methoxy-. N-methyls -6- (trifluoromethyl) pyridine-3-carboxamide：
By crude product 2- Ethylsulfanyls -6- (trifluoromethyl) pyridine -3- phosgenes (538mg, 2mmol), N, O- diformazans Base hydroxylamine hydrochloride (588mg, 6mmol) and K2CO3The mixture of (1.66g, 12mmol) in 10ml THF and 1ml water exists 10min is stirred at room temperature.Then the mixture is poured onto in water and is extracted with ethyl acetate three times.The organic layer of merging is used Sodium sulphate is dried, and is filtered and is concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide title compound (411mg, yield：70%).1H-NMR(300Mz,DMSO-d6):δ1.23(t,3H),3.10(q,2H),3.23(s,3H),3.45 (s,3H),7.64(d,1H),7.94(d,1H)；19F NMR(300Mz,DMSO-d6):δ-62.44(s,3F)。
Step C：1- [2- Ethylsulfanyls -6- (trifluoromethyl) -3- pyridine radicals] ethyl ketone：
At room temperature, to 2- Ethylsulfanyl-N- methoxy-. N-methyls -6- (trifluoromethyl) pyridine-3-carboxamide 1.4ml MeMgBr (3M is in THF) are added in the solution of (411mg, 1.4mmol) in 10ml THF, and allow to react this Stir 30min.Then the mixture is poured onto in water and is extracted with ethyl acetate three times.By the organic layer sodium sulphate of merging Dry, filter and be concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide title compound (290mg, production Rate：83%).1H-NMR(300Mz,DMSO-d6):δ1.22(t,3H),2.60(s,3H),3.02(q,2H),7.71(d,1H), 7.52(d,1H)；19F-NMR(300Mz,DMSO-d6):δ-67.93(s,3F)。
Step D：2- [2- Ethylsulfanyls -6- (trifluoromethyl) -3- pyridine radicals] -7- (trifluoromethyl) imidazos [1,2- A] pyridine：
By 1- [2- Ethylsulfanyls -6- (trifluoromethyl) -3- pyridine radicals] ethyl ketone (249mg, 1mmol), 4- (fluoroforms Base) pyridine -2- amine (162mg, 1.2mmol), Cu (OAc)2·H2O (12mg, 0.1mmol), ZnI2 (32mg, 0.1mmol) and 1, Mixture of the 10- phenanthrolenes (18mg, 0.1mmol) in 5ml dichloro-benzenes stirs 48h at 130 DEG C.Then by the mixture It is concentrated under vacuum, and the residue is purified by silica gel column chromatography, provides title compound (120mg, yield： 30%).1H NMR(300Mz,CDCl3):δ1.39(t,3H),3.29(q,2H),7.00(dd,1H),7.46(d,1H),7.94 (s,1H),8.27(d,1H),8.42(s,1H),8.47(d,1H)；19F NMR(300Mz,CDCl3):δ-69.33(s,3F),- 64.83(s,3F)；ESI-MS(+):392(M+H)+。
Step E：2- [2- ethylsulfonyls -6- (trifluoromethyl) -3- pyridine radicals] -7- (trifluoromethyl) imidazos [1,2- A] pyridine (compound V3.05)：
By compound 2- [2- Ethylsulfanyls -6- (trifluoromethyl) -3- pyridine radicals] -7- (trifluoromethyl) imidazo [1, 2-a] mixture of pyridine (156mg, 0.4mmol) and m-CPBA (277mg, 1.6mmol) in 10ml dichloromethane is in environment Temperature stirs 2 hours.Then the mixture is poured into NaHCO3And Na2SO3In saturated solution in water, and with acetic acid second Ester extracts three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.The residue is passed through into silicagel column Chromatographic purifying, to provide title compound (115mg, yield：68%).1H-NMR(300Mz,CDCl3):δ1.50(t,3H), 3.74(q,2H),7.01(dd,1H),7.95(s,1H),7.96(d,1H),8.27(d,1H),8.77(s,1H),8.92(d, 1H)；19F NMR(300Mz,CDCl3):δ-73.07(s,3F),-69.08(s,3F)；ESI-MS(+):424(M+H)+。 Mpt.188 DEG C of -190 DEG C of LCMS (method SQD 13):Rt.1.07 minutes, 424 (M+H).
Example P11：3- ethylsulfonyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] - 1,2,5- thiadiazoles (compound A1.014-B8.012)：
Step A：(2Z) -2- cyano group -2- oximidos-ethyl acetate：
At room temperature, by H3PO4(1.83mL, 27mmol) is added to cyan-acetic ester (5g, 44.2mmol) and NaNO2 In the mixture of (2.87g, 41.5mmol) in 35ml water.After the addition, the mixture is heated up to 40 DEG C and be stirred for One hour.Then, 3.69ml hydrochloric acid is added in the mixture, and continues stirring 18 hours.By the mixture diethyl ether Extraction is three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.The residue is passed through into silica gel column layer Analysis purifying, to provide title compound (4.3g, yield：69%).1H NMR(300Mz,DMSO-d6):δ1.28(t,3H),4.32 (q,2H)。
Step B：2- amino -2- cyano-acetic acid ethyl esters：
By Na2S2O4(17g, 105mmol) is added slowly to (2Z) -2- cyano group -2- oximidos-ethyl acetate (5g, 35mmol) And NaHCO3In the mixture of (1.5g, 17mmol) in 40ml water.Then 16h is stirred at room temperature in the mixture and uses chlorine Imitative extraction is three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum, to provide title compound (3.18g, yield 71%).1H NMR(300Mz,DMSO-d6):δ1.24(t,3H),3.53(s,2H),4.19(q,2H),4.81 (s,1H)。
Step C：The chloro- 1,2,5- thiadiazoles -3- Ethyl formates of 4-：
At ambient temperature, disulphur dichloride (4.06g, 30mmol) is added to 2- amino -2- cyano-acetic acid ethyl esters In the solution of (1.28g, 10mmol) in 10ml DMF.The mixture is stirred into 16h at ambient temperature and poured into ice, With dichloromethane extraction three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.The residue is led to Silica gel column chromatography purifying is crossed, to provide title compound (1.2g, yield：63%).1H NMR(300Mz,DMSO-d6):δ1.35 (t,3H),4.39(q,2H)。
Step D：4- Ethylsulfanyl -1,2,5- thiadiazoles -3- Ethyl formates：
By the Na in 10ml water2S·9H2O (2.4g, 10mmol) is added to the thiadiazoles -3- formic acid second of 4- chloro- 1,2,5- In solution of the ester (1.92g, 10mmol) in 30ml ethanol and by the mixture flow back 4h.Then by the mixture under vacuo Concentrate and add solution of the bromoethane (3.24g, 30mmol) in 10ml DMF.The reactant mixture is stirred in environment temperature 16 hours, pour into watery hydrochloric acid, and be extracted with ethyl acetate three times.The organic layer of merging is dried with sodium sulphate, filtering is simultaneously It is concentrated under vacuum.The residue is purified by silica gel column chromatography, to provide title compound (1.57g, yield：72%).1H NMR(300Mz,DMSO-d6):δ1.34(t,3H),1.36(t,3H),3.19(q,2H),4.37(q,2H)；ESI-MS(+): 219(M+H)+,241(M+Na)+。
Step E：4- Ethylsulfanyl -1,2,5- thiadiazoles -3- carboxylic acids：
By 4- Ethylsulfanyls -1,2,5- thiadiazoles -3- Ethyl formates (680mg, 3.12mmol) and LiOH (240mg, 10mmol) 2h is stirred at room temperature in the mixture in 5ml water and 5ml THF.Then, the reactant mixture is poured into dilute salt In acid, and it is extracted with ethyl acetate three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.Should Residue is purified by silica gel column chromatography, to provide product title compound (550mg, yield：93%).1H NMR(300Mz, DMSO-d6):δ1.35(t,3H),3.12(q,2H)。
Step F：3- Ethylsulfanyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] -1,2, 5- thiadiazoles (compound A1.014-B8.010)：
By 4- Ethylsulfanyls -1,2,5- thiadiazoles -3- carboxylic acids (570mg, 3mmol), N2- methyl -5- (trifluoromethyl) Pyridine -2,3- diamines (669mg, 3.5mmol, as prepared in WO 2012092051) and EDC.HCl (672mg, 3.5mmol) the mixture backflow 16h in 5ml pyridines.Then the mixture is concentrated under vacuum, and passes through silica gel column layer Analysis purifying, to provide title compound (621mg, yield：60%).1H-NMR(300Mz,DMSO-d6):δ1.41(t,3H), 3.27(q,2H),4.24(s,3H),8.73(s,1H),8.90(s,1H)；19F NMR(300Mz,DMSO-d6):δ-53.72(s, 3F)；ESI-MS(+):346(M+H)+.LCMS (method SQD13)：Rt.1.21 minutes, 346 Mpt.188 DEG C -189 DEG C of (M+H).
Step G：3- ethylsulfonyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine -2- bases] -1,2, 5- thiadiazoles (compound A1.014-B8.012)：
By in 10ml DCM 3- Ethylsulfanyls -4- [3- methyl -6- (trifluoromethyl) imidazo [4,5-b] pyridine - 2- yls] -1,4h is stirred at room temperature in 2,5- thiadiazoles (0.87mmol, 300mg) and m-CPBA (519mg, 3mmol).Then will The mixture pours into NaHCO3And Na2SO3In saturated solution in water, and it is extracted with ethyl acetate three times.By having for merging Machine layer is dried with sodium sulphate, is filtered and is concentrated under vacuum.The residue is purified by silica gel column chromatography, it is titled to provide Compound (147mg, 75%).1H NMR(300Mz,DMSO-d6):δ1.31(t,3H),3.97(q,2H),4.00(s,3H),8.76 (s,1H),8.94(s,1H)；19F NMR(300Mz,DMSO-d6):δ-53.85(s,3F)；ESI-MS(+):378(M+H)+,400 (M+Na)+,432(M+Na+MeOH)+.LCMS (method SQD13)：Rt.0.93 minutes, 378 Mpt.144 DEG C -146 DEG C of (M+H)
Example P12：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) [1,2,4] three Azoles simultaneously [1,5-c] pyrimidine (compound V16.03)：
Step A：4- (trifluoromethyl) pyrimidine -1--1,6- diamines, 2,4,6- tri-methyl p-toluenesulfonates salt (MSH)：
Pay attention to：MSH as dry powder is explosive unstable, and is preferably handled in dichloromethane solution.
2,2,2- trifluoroacetic acids (4.4g, 2.54mmol, 2.9mL) are loaded into the microwave equipped with a magnetic stirring bar Pipe.Then, (t-butoxycarbonyl amino) 2,4,6- tri-methyl p-toluenesulfonate salt (1g, 2.54mmol) is added at 0 DEG C.The reaction is mixed Compound stirs 2h at 0 DEG C, adds ice-water, and sediment is recovered by filtration.Wet cake is washed with water, and is dissolved in dichloro In methane (5mL), and dried with sodium sulphate.At 0 DEG C, to 6- (trifluoromethyl) pyrimidine -4- amine (0.3723g, such as in WO Prepared in 2007113558) resulting solution is added dropwise in agitating solution in dichloromethane (5mL).1 hour at 0 DEG C At room temperature after a night (white suspension), the reactant mixture is diluted with diethyl ether (8mL), and is recovered by filtration Sediment, to obtain title compound (0.791g, 82%).
Step B：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl)-[1,2,4] triazole And [1,5-c] pyrimidine (compound V16.03)：
4- (trifluoromethyl) pyrimidine -1--1,6- diamines, 2,4,6- tri-methyl p-toluenesulfonate salt (0.3g, 0.791mmol), 3- ethylsulfonyls -5- (trifluoromethyl) pyridine-2-carboxylic acids (0.33593g, 1.1861mmol) and 3- (ethylimino methylenes Base amino)-N, N- dimethyl -propyl- 1- amine salt acidulants (0.1819098g, 0.9489mmol) are dissolved in pyridine (2mL), and 3h is heated at 120 DEG C.At this moment after, the reactant mixture is poured onto it is waterborne, by water layer with EtOAc extract three times.It will close And organic layer priority water and salt water washing, use Na2SO4Dry, filter and be concentrated under vacuum.By crude product diethyl ether Grind and filter, to provide white powdered product (110mg, 33%).
1H NMR(400MHz,CDCl3):δ (ppm) 9.31 (d, J=2.2Hz, 1H), 9.17 (d, J=1.5Hz, 1H), 8.34-8.53 (m, 1H), 3.23 (q, J=7.5Hz, 2H), 1.37 (t, J=7.5Hz, 3H).LCMS (method SQD13)：Rt: 0.94min,426(M+H)。Mpt.:190℃-192℃
Example P13：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) oxazoles simultaneously [5, 4-c] pyridine (compound V12.05)：
Step A：4- nitros -6- (trifluoromethyl) pyridine -3- alcohol：
At 0 DEG C, to solution of 6- (trifluoromethyl) pyridine -3- alcohol (5.00g, 30.7mmol) in sulfuric acid (92.0mL) Middle addition ice (25.0g, 1390mmol), keeps the temperature at less than 10 DEG C.Into the solution add nitric acid (2.97g, 2.14mL, 30.7mmol), and the mixture is heated 4 hours at 85 DEG C.Add Part II nitric acid (2.97g, 2.14mL, 30.7mmol), and by the reaction at 85 DEG C it is stirred overnight.Lcms analysis shows about 40% conversion, and therefore adds nitric acid (2.97g, 2.14mL, 30.7mmol), and the reaction is stirred into 5h at 85 DEG C.Add another part nitric acid (2.97g, 2.14mL, 30.7mmol), and the reaction is stirred overnight at 85 DEG C.At this moment after, the mixture is poured into frozen water simultaneously With 250ml Et2O is extracted.By the organic phase sodium sulphate drying of merging and it is concentrated under vacuum.The residue is passed through quick Chromatographic purifying, with dichloromethane eluent, to provide title compound (18% yield).1H NMR(400MHz,CDCl3):10.32 (s,1H),8.82(s,1H),8.30(s,1H)ppm。
Step B：4- amino -6- (trifluoromethyl) pyridine -3- alcohol：
Under argon, to 4- nitros -6- (trifluoromethyl) pyridine -3- alcohol (1.15g, 5.53mmol) in ethanol (50mL) and four Palladium carbon (0.12g) is added in solution in hydrogen furans (10mL).Stirred at room temperature using nitrogen atmosphere (balloon), and by the mixture Mix overnight.After completing to reduce, the mixture is filtered with diatomite, and filter cake is washed with ethanol.By solvent in vacuum Lower removal is simultaneously purified the residue by flash chromatography (cyclohexane/ethyl acetate), to provide the titled of glue that take on a red color Compound (0.98g, quantitative).1H NMR(400MHz,CDCl3):7.92(s,1H),6.92(s,1H),4.75(s,2H)ppm。
Step C：2- [3- Ethylsulfanyls -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) oxazoles simultaneously [5,4- C] pyridine.(compound A6.006-B1.014)：
By 4- amino -6- (trifluoromethyl) pyridine -3- alcohol (100mg, 0.56mmol) and 3- Ethylsulfanyl -5- (trifluoros Methyl) pyridine-2-carboxylic acids (155mg, 0.62mmol, as prepared in WO 2013018928) are molten in polyphosphoric acid (2mL) Liquid stirs 24 hours at 185 DEG C.Then the reactant mixture is poured into water (50mL) with vigorous stirring, and pH is used NaOH (2N) is adjusted to 8.Aqueous phase is extracted with dichloromethane (x2), and the organic phase of merging is dried with sodium sulphate.In vacuum Lower evaporation solvent, and the residue is purified by flash chromatography (cyclohexane/ethyl acetate), to provide title compound (75mg, 34%).
1H NMR(400MHz,CDCl3):9.20(s,1H),8.82(s,1H),8.32(s,1H),7.98(s,1H),3.14 (q,2H),1.54(t,3H)ppm.LCMS (method SQD13)：Rt:1.15min, 394 (M+H).
Step D：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) oxazoles simultaneously [5,4- C] pyridine (compound V12.05)：
To 2- [3- Ethylsulfanyls -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) oxazoles simultaneously [5,4-c] pyrroles M-CPBA (83mg, 0.34mmol) is added in solution of the pyridine (60mg, 0.153mmol) in dichloromethane (10mL).By gained Yellow solution is stirred at room temperature 1 hour, and then adds 60mg m-CPBA again.The reactant mixture is stirred in room temperature 2h, and then pour into the saturated solution of potassium carbonate.Aqueous phase is extracted twice with dichloromethane, and by the organic of merging Mutually dried, and be concentrated under vacuum with sodium sulphate.The residue is purified by flash chromatography (cyclohexane/ethyl acetate), with Provide white powdered title compound (49mg, 75%) (75%).
1H NMR(400MHz,CDCl3):9.28(s,1H),9.22(s,1H),8.84(s,1H),8.24(s,1H),3.98 (q,2H),1.48(t,3H)ppm.LCMS (method SQD13)：Rt.1.02min, 426 (M+H+).
Example P14：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) imidazo [1, 2-c] pyrimidine (compound V16.02)：
Step A：1- [3- Ethylsulfanyls -5- (trifluoromethyl) -2- pyridine radicals] ethyl ketone：
By bromine (methyl) magnesium, (1.4M is in THF:Toluene 1:In 3,14Ml, 18.95mmol) in dry toluene (90mL) Solution be cooled to 0 DEG C, and dropwise with 3- Ethylsulfanyls -5- (trifluoromethyl) pyridine -2- formonitrile HCNs (4.00g, 17.23mmol, As prepared in WO 2013018928) solution that is dissolved in 30ml toluene handled.Allow to stir the reaction at 0 DEG C Mix 30min.At this moment after, lcms analysis display reaction is completed.The reactant mixture is slowly used into NH4Cl saturations are water-based (50ml) and HCl 10% (30ml) are quenched, and gained mixture is stirred vigorously into 15min in room temperature.Water layer is extracted with EtOAc Take twice, and the organic phase of merging is used into anhydrous Na successively with 10% water-based HCl, water and salt water washing2SO4Dry, filtering is simultaneously It is concentrated under vacuum.It is used for next step by thick title product (4.335g, 91%) is not purified.
1H NMR(400MHz,CDCl3):δ (ppm) 8.62 (s, 1H), 7.85 (d, J=1.1Hz, 1H), 2.96 (q, J= 7.3Hz, 2H), 2.74 (s, 3H), 1.43 (t, J=7.5Hz, 3H).LCMS (method SQD13)：Retention time 1.05min, 250 (M+H)。
Step B：1- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] ethyl ketone：
At 0 DEG C, m-CPBA (24.29g, 98.53mmol) is added to 1- [3- Ethylsulfanyl -5- (fluoroforms portionwise Base) -2- pyridine radicals] in solution of the ethyl ketone (11.98g, 48.06mmol) in chloroform (400mL) (at 0 DEG C).Allow gained mixed Compound is heated up to room temperature and stirs 20h.Then by the reactant mixture water-based NaHCO of 200mL3With 50mL saturation thiosulfuric acids Sodium water solution is quenched, and with EtOAc extractions three times.By the organic phase of merging successively with water-based NaHCO3With salt water washing, use Na2SO4Dry and be concentrated under vacuum.Purifying (uses EtOAc/ heptan on 220g posts on mighty torrent machine (torrent machine) Alkane elutes), provide the title compound (8.5g, 63%) of white solid-like.
1H NMR(400MHz,CDCl3):δ (ppm) 9.07 (d, J=1.1Hz, 1H), 8.59 (d, J=1.5Hz, 1H), 3.58 (q, J=7.3Hz, 2H), 2.74 (s, 3H), 1.38 (t, J=7.5Hz, 3H).LCMS (method SQD13)：Retention time 0.87min, 282 (M+H).
Step C：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) imidazos [1,2- C] pyrimidine：
By 6- (trifluoromethyl) pyrimidine -4- amine (232mg, 1.0607mmol, as prepared in WO 2007113558), 1- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] ethyl ketone (200mg, 0.71mmol), cupric iodide (I) (7.0mg, 0.036mmol), trifluoromethayl sulfonic acid In (III) (4.0mg, 0.0071mmol) and 1-Methyl-2-Pyrrolidone (4mL) is mixed Compound stirs 19 hours at 120 DEG C.LC-MS：Desired product and parent material, and thus by the reaction at 120 DEG C again Stirring 27 hours.Reactant mixture is cooled to environment temperature, and adds water and ethyl acetate.Aqueous layer with ethyl acetate is extracted 2 times, and by the organic layer of merging salt water washing, use Na2SO4Dry, filter and be concentrated under vacuum.The product is passed through Combiflash chromatographies are purified with the gradient of 12g post and hexamethylene+0-80% ethyl acetate, to provide white solid The title compound (96mg, 31%) of shape.1H NMR(400MHz,CDCl3):δ(ppm)9.20(s,1H),9.14(s,1H), 8.80 (d, J=1.5Hz, 1H), 8.44 (s, 1H), 7.99 (s, 1H), 4.10 (q, J=7.5Hz, 2H), 1.43 (t, J= 7.5Hz,3H).LCMS (method SQD13)：Rt：0.98min, 425 (M+H).Mpt.180℃-181℃.
Example P15：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -3- methyl -7- (trifluoromethyl) miaow Azoles simultaneously [1,2-c] pyrimidine (compound V16.01)：
Step A：The bromo- 2- of 3- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) imidazo [1,2-c] pyrimidine：
2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) imidazo [1,2-c] is phonetic Pyridine (52mg, 0.123mmol) is dissolved in acetonitrile (1mL), and at ambient temperature with N-bromosuccinimide (24.5mg, 0.135mmol) handle.Reactant mixture is stirred at room temperature overnight.The reactant mixture is concentrated under vacuum, and passed through Combiflash chromatographies are purified with the gradient of 4g post and hexamethylene+0-50% ethyl acetate.Obtain white solid-like Title product.
1H NMR(400MHz,CDCl3):δ (ppm) 9.22 (d, J=0.7Hz, 1H), 9.20 (s, 1H), 8.77 (d, J= 1.5Hz, 1H), 7.94 (s, 1H), 4.00 (q, J=7.6Hz, 2H), 1.40-1.47 (t, J=7.6Hz, 3H).LCMS (methods SQD13)：Rt：1.04min, 503/505 (M+H).
Step B：The bromo- 2- of 3- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) imidazo [1,2-c] pyrimidine (compound V16.01)：
By the bromo- 2- of 3- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- (trifluoromethyl) imidazos [1,2- C] the suspension argon of pyrimidine (100mg, 0.199mmol) and potassium carbonate (84mg, 0.60mmol) in the dioxane of Isosorbide-5-Nitrae-(3mL) 10min is purged, and then with 2,4,6- trimethyls -1,3, the boron azacyclohexane of 5,2,4,6- trioxa three (trioxatriborinane) (30.0mg, 0.24mmol, 0.0332mL) and Pd (Ph3) 4 (23mg, 0.02mmol) processing.Will The reactant mixture heats 12 hours at 95 DEG C.Lcms analysis shows desired product and parent material, and thus will The mixture cools down and purges 10min with argon, and with 2,4,6- trimethyls -1,3, the boron azacyclohexane of 5,2,4,6- trioxa three (trioxatriborinane) (30.0mg, 0.24mmol, 0.0332mL) and Pd (Ph3) 4 (23mg, 0.02mmol) processing.Will The reactant mixture is reheated 5 hours at 95 DEG C until reaction is completed.By reactant mixture NH4Cl saturated solutions and water are dilute Release, and be then extracted with ethyl acetate three times.By the organic layer of merging salt water washing, Na is used2SO4Dry, filter and true Sky is lower to be concentrated.By product by combiflash chromatograph with the gradient of 12g post and hexamethylene 0-50% ethyl acetate carry out it is pure Change.This provides the title product (51mg, 59%) of white solid-like.1H NMR(400MHz,CDCl3):δ(ppm)9.17(d,J =1.5Hz, 1H), 9.01 (s, 1H), 8.77 (d, J=1.5Hz, 1H), 4.10 (q, J=7.6Hz, 2H), 2.78 (s, 3H), 1.40-1.47 (t, 7.6Hz, 3H) .LCMS (method SQD13)：Rt：1.01min, 439 (M+H).Mpt.240℃-242℃.
Example P16：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -1- methyl -5- (trifluoromethyl) miaow Azoles simultaneously [4,5-b] pyrazine (compound A1.026-B1.022)：
Step A：The iodo- N- Methyl-pyrazins -2- amine of 3,5- bis-：
At 10 DEG C, to N- methylpyrazine -2- amine (1g, 9.2mmol) in dimethyl sulfoxide (20ml)/water (0.4ml) N- iodine succinimide (4.1g, 18.4mmol) is added in agitating solution portionwise.Then the reactant mixture is allowed slowly to heat It is stirred overnight to room temperature and at such a temperature.Then the another of N- iodine succinimide (4.1g, 18.4mmol) is added at room temperature Outer aliquot.After stirring 7 hours, the reactant mixture is poured onto on ice (20g).Sediment is collected, uses cold water (20ml) is washed, and is dried, to provide title compound (2.15g, 65%).1H NMR(300MHz,DMSO-d6)δ(ppm)： 8.14 (s, 1H), 6.69 (br, 1H), 2.77 (d, 3H, J=4.5Hz)；ESI-MS(-):360.
Step B：The iodo- N2- Methyl-pyrazins -2,3- diamines of 5-：
Will be in the NH in EtOH (15ml)3(gas) added to the iodo- N- Methyl-pyrazins -2- amine of 3,5- bis- (2.15g, In 6mmol), and the mixture is heated to 150 DEG C of lasting 18h in seal pipe.After the solution is cooled down, dichloromethane is added Alkane and water (1:1,200ml).Aqueous phase is extracted with dichloromethane (50ml), and by the organic layer Na of merging2SO4It is dry and dense Contracting, to provide the title compound of white solid-like.(1.19g, 80%).1H NMR(300MHz,DMSO-d6)δ(ppm)： 7.41(s,1H)6.35(br,3H),2.78(s,3H)；ESI-MS(-):249,ESI-MS(+):251.
Step C：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] iodo- 1- methyl-imidazoles of -5- simultaneously [4,5- B] pyrazine：
By the method described in above example, from iodo- N2- Methyl-pyrazins -2, the 3- diamines of 5- and 3- ethylsulfonyls - The compound is prepared in 5- (trifluoromethyl) pyridine-2-carboxylic acids.
Step D：2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -1- methyl -5- (trifluoromethyl) imidazoles And [4,5-b] pyrazine (compound A1.026-B1.022)：
By compound 2- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] iodo- 1- methyl-imidazoles of -5- simultaneously [4, 5-b] pyrazine (497mg, 1mmol), FSO2CF2COOMe (384mg, 2m mol) and CuI (191mg, 1mmol) are in 5ml DMF Mixture stir 24h under nitrogen atmosphere at 120 DEG C.Then, the mixture is poured into watery hydrochloric acid, and extracted with ethyl acetate Take three times.The organic layer of merging is dried with sodium sulphate, filters and is concentrated under vacuum.Crude product is pure by silica gel column chromatography Change, to provide title compound (197.5mg, yield：45%).1H NMR(300MHz,CDCl3)δ(ppm)：9.26(s,1H), 8.88 (s, 1H), 8.75 (s, 1H), 3.98 (m, 5H), 1.42 (t, J=6.9Hz, 3H).19F NMR(300Mz,CDCl3)δ (ppm)：-62.15；-65.18.ESI-MS:440(M+H),462(M+Na+).Mpt.162℃-165℃.LCMS (methods SQD13)：Rt.1.04 minutes, 440 (M+H).
Example P17：3- methyl -2- [3- (sulfonyloxy methyl ylmethyl) -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoros Methyl) imidazo [4,5-b] pyridine (compound is A.014-B1.106)：
By 3- methyl -5- (trifluoromethyl) pyridine -2- Ethyl formates (1.0g 4.29mmol, such as in JACS (J.Amer.Chem.Soc.), 2013, prepared described in 135,12122-12134) be dissolved in acetonitrile (40ml), it is used in combination N- bromines succinamide (1.21g, 6.43mmol) and benzoyl peroxide (0.150g, 0.600mmol) processing.Use sunlamp The reactant mixture is irradiated, is heated at reflux (75 DEG C of bath temperatures).After 10 hours, the mixture is cooled down, filtered, and Reduced under vacuum.By crude product (1.27g) (it mainly includes 3- (bromomethyl) -5- (trifluoromethyl) pyridine -2- Ethyl formates) It is used for next step without further purification.
3- (bromomethyl) -5- (trifluoromethyl) pyridine -2- Ethyl formates (0.5g, 1.6mmol, made above) are dissolved in In DMF, 0 DEG C is cooled to, and handled with sodium methyl mercaptide (0.22g, 3.2mmol).Allow the mixture being heated up to room temperature, and stir Mix overnight.By the reactant mixture with water-based NH4Cl dilutes, and is extracted with TBME (2x).By the remaining water layer water-based HCl of 6N Acidifying, and extracted 3 times with dichloromethane.By the dichloromethane layer Na of merging2SO4Dry, filter and evaporate, to provide 0.31g Buff white solid, the solid bag is containing desired 3- (methylsulfanyl methyl) -5- (trifluoromethyl) pyridine-2-carboxylic acids.By its It is used for next step without further purification.
By N2- methyl -5- (trifluoromethyl) pyridine -2,3- diamines (0.24g, 1.3mmol, such as in WO2012092051 Prepare), EDC.HCl (0.24g, 1.3mmol) and 3- (methylsulfanyl methyl) -5- (trifluoromethyl) pyridine-2-carboxylic acids (0.29g, the crude samples more than) are dissolved in pyridine (15ml).The brown suspension is stirred into 2h at 120 DEG C.This is anti- Answer mixture to be diluted with water, and extracted with EtOAc.Organic layer is separated, and with salt water washing, uses Na2SO4Dry and evaporate.Will be thick Product is purified by the machines of RF 200 chromatography (using EtOAc/ hexamethylenes gradient elution), and to provide 0.35g buff white solids, this is solid Body include desired product N- [2- (methylamino) -5- (trifluoromethyl) -3- pyridine radicals] -3- (methylsulfanyl methyl) - 5- (trifluoromethyl) pyridine-2-carboxamide.The product has been dissolved in the 1- first of toluene-4-sulfonic acid (0.072g, 0.41mmol) In base pyrrolidin-2-one (5ml), and 1h is heated at 160 DEG C in microwave.At this moment it is after, the reactant mixture water is dilute Release, and extracted with EtOAc.By organic layer water and salt water washing, with sodium sulphate drying and it is concentrated under vacuum.With silica gel barrel mast (Rf200) purify, eluted with hexamethylene/EtOAc, provide 3- methyl -2- [3- (the methylsulfanyl first of white solid-like Base) -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) imidazo [4,5-b] pyridine (140mg).LCMS (methods SQD13)：Rt.1.17 minutes, 407 (M+H).
By 3- methyl -2- [3- (methylsulfanyl methyl) -5- (trifluoromethyl) -2- pyridine radicals] -6- (trifluoromethyl) miaow Simultaneously solution of [4, the 5-b] pyridine (100mg, 0.25mmol) in dichloromethane is cooled to 0 DEG C to azoles, and adds MCPBA at 0 DEG C (61mg, 0.25mmol).After 1h, LC/MS shows sulfoxide and sulfone, and thus adds 61mg MCPBA again.Completed in reaction When, by mixture 2M Na2CO3It is quenched with dichloromethane.Organic layer is separated, is washed with water once, uses Na2SO4Dry, mistake Filter and be concentrated under vacuum.Purified with silica gel barrel mast (Rf200), eluted with hexamethylene/EtOAc, provide white solid-like Title compound (80mg, 70%).LCMS (method SQD13)：Rt.1.02 minutes, 439 (M+H).1H NMR(400MHz, CDCl3):δ (ppm) 9.08 (d, J=1.5Hz, 1H), 8.79 (d, J=1.5Hz, 1H), 8.34-8.36 (m, 1H), 8.33 (d, J =1.8Hz, 1H), 5.25 (s., 2H), 4.13 (s, 3H), 2.93 (s, 3H).
Example P18：The bromo- 2- of 6- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -3- methyl-imidazoles simultaneously [4, 5-c] pyridine (compound V12.20)：
Step A：The fluoro- 1- oxidations-pyridine -1- of the bromo- 5- of 2-：
At 0 DEG C, into agitating solution of the bromo- 5- fluorine pyridines (5.0g, 28.4mmol) of 2- in TFA (10.0mL) dropwise Add H2O2(30%, 15mL), the mixture is stirred overnight under reflux.After cooling, the reaction system is poured onto In ice-water, with methylene chloride/methanol (10:1,50mL x 3) extraction, organic layer saturated sodium bicarbonate solution and salt are washed Wash, and use anhydrous sodium sulfate drying.After filtering and being concentrated under vacuum, by crude product (pale solid, 4.6g, yield： 84%) it is used for next step without further purification.
Step B：The fluoro- 4- nitros -1- oxidations-pyridine -1- of the bromo- 5- of 2-：
At 0 DEG C, to the fluoro- 1- oxidations of the bromo- 5- of 2--pyridine -1- (4.6g, 23.9mmol) in sulfuric acid (dense) (20mL) Solution in be slowly added fuming nitric aicd (10mL).After the addition, the reaction temperature rises to 120 DEG C, and at this temperature after Continuous stirring 4h.After cooling to room-temperature, the reaction solution is poured onto in ice-water.By pH value NH4OH is adjusted to 1.Filtering Sediment, and oven drying, to obtain the title compound (2.3g, 40%) in faint yellow solid shape.
Step C：The bromo- N- methyl -4- nitros -1- oxidations of 6--pyridine -1--3- amine：
To the fluoro- 4- nitros -1- oxidations of the bromo- 5- of 2--solution of the pyridine -1- (1.1g, 4.6mmol) in ethanol (10mL) Middle addition MeNH2/ ethanol (4mL).4h is stirred at room temperature in the reactant mixture.The mixture is concentrated under vacuum, with to It is in the title compound of solid-like to go out, and it is used for into next step without further purification.
Step D：The bromo- N- methyl -4- nitro-pyridines -3- amine of 6-：
To the bromo- N- methyl -4- nitros -1- oxidations of 6--pyridine -1--3- amine (thick more than, 4.6mmol) in PBr (1.0mL) is added in solution in dichloromethane (10mL).The reactant mixture is stirred 1 hour at ambient temperature.Will The mixture is dried under vacuum, and to provide the title compound in Chinese red solid-like, and it is used without further purification In next step.
Step E：The bromo- N3- methvl-pyridiniums -3,4- diamines of 6-：
Add into solution of the bromo- N- methyl -4- nitro-pyridines -3- amine of 6- (crude product, 4.6mmol) in methanol (10mL) Add Raney's nickel (Raney Ni) (20%wt), and hydrazine hydrate (1.0mL) is added dropwise at 0 DEG C.By the reactant mixture in room temperature Lower stirring a few minutes.Raney's nickel (Raney Ni) is filtered out by diatomite；Filtrate is dried under vacuum, and uses silica gel column layer Analyse (dichloromethane:Methanol, 10:1) purify, with obtain in lavender solid-like title compound (0.6g, three step yields, 63%).1H NMR(400MHz,DMSO-d6):δ(ppm)7.20(s,1H),6.65(s,1H),6.54(brs,2H),3.34(s, 1H), 2.69 (d, J=6.4Hz, 3H).ESI-MS(+):203(M+H).
Step F：N- (the bromo- 3- pyridine radicals of 4- amino -6-) -3- ethylsulfonyl-N- methyl -5- (trifluoromethyl) pyridine - 2- formamides：
To bromo- N3- methvl-pyridiniums -3, the 4- diamines (0.60g, 2.96mmol) of 6-, 3- ethylsulfonyl -5- (fluoroforms Base) pyridine-2-carboxylic acids (0.92g, 3.26mmol, as prepared in WO 2013180194) and HATU (1.4g, 3.68mmol) DIPEA (1.2ml, 7.26mmol) is added in agitating solution in DMF (5.0mL).The system is stirred at room temperature overnight. By the reaction EtOAc and H2O dilutes, and by organic layer salt solution and water washing, uses anhydrous sodium sulfate drying.In filtering and true After the lower concentration of sky, the thick title product is used for next step without further purification.
Step G：The bromo- 2- of 6- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -3- methyl-imidazoles simultaneously [4,5- C] pyridine (compound V12.20)：
By N- (the bromo- 3- pyridine radicals of 4- amino -6-) -3- ethylsulfonyl-N- methyl -5- (trifluoromethyl) pyridine -2- first Solution of the acid amides (crude product, 2.96mmol) in acetic acid (5.0mL) is stirred overnight at 120 DEG C.The mixture is evaporated to drying. The residue is passed through into purified on silica (petroleum ether:EtOAc=4:1), to obtain the title compound of white solid-like (0.65g, two step yields：48%).1H NMR(400MHz,DMSO-d6):δ(ppm)9.53(s,1H),8.94(s,1H), 8.74 (s, 1H), 8.01 (s, 1H), 3.83 (q, J=7.6Hz, 2H), 3.79 (s, 3H), 1.19 (t, J=7.2Hz, 3H).19F NMR(300MHz,DMSO-d6):δ(ppm)-60.42(s,3F).ESI-MS(+):449(M+H),472(M+Na)；ESI-MS (-):447(M-H).Mpt.188℃-190℃.LCMS (method SQD13)：Rt.0.95min, 451 (M+H).
Example P19：The chloro- 6- of 3- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- methyl-imidazoles simultaneously [4, 5-c] pyridazine (compound V12.17)
Step A：3,6- dichloro-pyridazine -4- amine
Bromo- 3,6-, the bis- chloro- pyridazines (15.0g, 65.8mmol, as prepared in WO 2008116815) of 4- are dissolved in In EtOH (73.1mL), and it is incorporated into autoclave.At room temperature, the NH of gas is introduced3(4.48g, 263mmol), and And then the reactant mixture is stirred overnight under reflux.The solution is concentrated under vacuum, and by residue EtOAc Grinding, insoluble Partial filtration is fallen, and evaporates mother liquor, to provide crude product.By it by flash chromatography, hexamethylene is used Alkane/EtOAc 1/1+2.5%Et3N elutions, to provide the title compound (5.82g, 53%) in light brown solid.LCMS (method ZCQ13)：Rt.0.3min, 164/166/168 (M+H).
Step B：The chloro- N3- methyl-pyridazins -3,4- diamines of 6-
In autoclave, by 3,6- dichloro-pyridazine -4- amine (2.35g, 14.3mmol) be dissolved in EtOH (20.2g, 215mmol, 26.7mL) in methylamine processing, and be heated to 100 DEG C.At 100 DEG C after 48h, LCMS no longer shows starting Material.The reactant mixture is evaporated to drying.The crude product is diluted in dichloromethane, and adds 4ml Et3N.Should Mixture is stirred at room temperature 5' and evaporated.The residue is diluted with 5ml water, and by insoluble filtration of material, and dried, with to It is in the title product (1.35g, 57%) of light brown solid to go out.LCMS (method ZCQ13)：Rt.0.17min, 157/159 (M- H)。
Step C：N- [6- chloro- 3- (methylamino) pyridazine -4- bases] -3- Ethylsulfanyls -5- (trifluoromethyl) pyridines -2- Formamide
Chloro- N3- methyl-pyridazins -3, the 4- diamines (0.3g, 1.89mmol) of 6- that will be dissolved in pyridine (14.6mL) use 3- Ethylsulfanyl -5- (trifluoromethyl) pyridine-2-carboxylic acids (0.499g, 1.99mmol, as prepared in WO 2013018928) With EDCI.HCl (0.4352g, 2.27mmol) processing.4h is stirred at room temperature in the reactant mixture, and then with other portion EDCI.HCl (0.4352g, the 2.27mmol) processing divided.The mixture is stirred at room temperature overnight.Then the reaction is mixed Thing reduced under vacuum, and the residue is absorbed in EtOAc and water.Separate each phase and by the organic phase salt water washing, use Na2SO4Dry, and be concentrated under vacuum.The crude product is passed through into Flash-Master (solvents：Hexamethylene/EtOAc 3/1 is carried out Purifying, to provide the title compound of white solid-like (250mg, 33%).LCMS (method ZCQ13) retention time 1.01min, 392/394 (M+H).
Step D：The chloro- 6- of 3- [3- Ethylsulfanyls -5- (trifluoromethyl) -2- pyridine radicals] -7- methyl-imidazoles simultaneously [4,5- C] pyridazine (compoundA6.015-B1.014)
By N- [6- chloro- 3- (methylamino) pyridazine -4- bases] -3- Ethylsulfanyls -5- (trifluoromethyl) pyridine -2- formyls Amine (250mg, 0.64mmol) is dissolved in DMF (2mL) and toluene (8mL).Addition p-methyl benzenesulfonic acid monohydrate (0.123g, 0.70mmol).Bomb pipe is closed, and is heated to 160 DEG C and continues 4 hours.It is then cooled to room temperature and is evaporated to drying. The residue is passed through into Flash-Master (solvents：Hexamethylene/EtOAc 2/1) purified, it is in yellow solid to provide Title compound (172mg, 72%).
1H NMR(400MHz,CDCl3):δ(ppm)8.65-8.88(m,1H),7.86-8.05(m,2H),4.13-4.27 (m, 3H), 3.04 (q, J=7.5Hz, 2H), 1.41 (t, J=7.5Hz, 3H).LCMS (method ZCQ13)：Retention time 1.01min, 374/376 (M+H).Mpt.:156℃-158℃.
Step D：The chloro- 6- of 3- [3- ethylsulfonyls -5- (trifluoromethyl) -2- pyridine radicals] -7- methyl-imidazoles simultaneously [4,5- C] pyridazine (compound V12.17)
By the chloro- 6- of 3- [3- Ethylsulfanyls -5- (trifluoromethyl) -2- pyridine radicals], simultaneously [4,5-c's -7- methyl-imidazoles] rattles away Piperazine (0.14g, 0.3745mmol) is dissolved in dichloromethane (8mL).At 0 DEG C, addition MCPBA (0.1747g, 0.7491mmol), and by the mixture at 0 DEG C 1h is stirred, 3h is then stirred at room temperature.By reaction saturation thiosulfuric acid Sodium solution is quenched.By the organic phase of separation saturation NaHCO3 and salt water washing, Na is used2SO4Dry, filter and dense under vacuo Contracting.The crude product is passed through into Flash-Master (solvents：Hexamethylene/EtOAc 1/1) purified, to provide white solid The title compound (164mg, 96%) of shape.1H NMR(400MHz,CDCl3):δ (ppm) 9.28 (d, J=1.5Hz, 1H), 8.78 (d, J=1.8Hz, 1H), 7.71-8.03 (m, 1H), 4.02 (s, 3H), 3.84 (q, J=7.6Hz, 2H), 1.40 (t, J= 7.5Hz,3H).LCMS (method ZCQ13)：Retention time 0.91min, 406/408 (M+H).Mpt.228℃-229℃.
Specifically the example of the compound with chemical formula (I) shows that wherein Table A to K describes base in table 1 below to 130 Group B, and table L to Q describes group A：
A-B(I)
Table AWith chemical formula B1Group (DB represents a direct key, i.e. the sulphur is attached directly to aromatic rings)
Table B：With chemical formula B2Group
Table C：With chemical formula B3Group
Table D：With chemical formula B4Group
Group R12 V1 V2
B4.001 CH3 N C-H
B4.002 CH3 N C-CF3
B4.003 CH3 N C-Br
B4.004 CH3 N C-Cl
B4.005 CH3 C-H C-H
B4.006 CH3 C-H C-CF3
B4.007 CH3 C-H C-Br
B4.008 CH3 C-H C-Cl
Table E：With chemical formula B5Group
Table F：With chemical formula B6Group
Group R19 V1 V2
B6.001 C(CH3)3 N C-H
B6.002 C(CH3)3 N C-CF3
B6.003 C(CH3)3 N C-Br
B6.004 C(CH3)3 N C-Cl
B6.005 C(CH3)3 C-H C-H
B6.006 C(CH3)3 C-H C-CF3
B6.007 C(CH3)3 C-H C-Br
B6.008 C(CH3)3 C-H C-Cl
B6.009 H N C-H
B6.010 H N C-CF3
B6.011 H N C-Br
B6.012 H N C-Cl
B6.013 H C-H C-H
B6.014 H C-H C-CF3
B6.015 H C-H C-Br
B6.016 H C-H C-Cl
Table G：With chemical formula B7Group
Table H：With chemical formula B8Group
Group R3 V5 V6 m
B8.001 CH3 C-H C-H 0
B8.002 CH3 C-H C-H 1
B8.003 CH3 C-H C-H 2
B8.004 CH2CH3 C-H C-H 0
B8.005 CH2CH3 C-H C-H 1
B8.006 CH2CH3 C-H C-H 2
B8.007 CH3 C-H N 0
B8.008 CH3 C-H N 1
B8.009 CH3 C-H N 2
B8.010 CH2CH3 C-H N 0
B8.011 CH2CH3 C-H N 1
B8.012 CH2CH3 C-H N 2
Table I：With chemical formula B9Group
Group R3 V8 V7 m
B9.001 CH3 C-H C-H 0
B9.002 CH3 C-H C-CF3 0
B9.003 CH3 C-H C-Br 0
B9.004 CH3 C-H C-Cl 0
B9.005 CH3 C-H C-H 1
B9.006 CH3 C-H C-CF3 1
B9.007 CH3 C-H C-Br 1
B9.008 CH3 C-H C-Cl 1
B9.009 CH3 C-H C-H 2
B9.010 CH3 C-H C-CF3 2
B9.011 CH3 C-H C-Br 2
B9.012 CH3 C-H C-Cl 2
B9.013 CH2CH3 C-H C-H 0
B9.014 CH2CH3 C-H C-CF3 0
B9.015 CH2CH3 C-H C-Br 0
B9.016 CH2CH3 C-H C-Cl 0
B9.017 CH2CH3 C-H C-H 1
B9.018 CH2CH3 C-H C-CF3 1
B9.019 CH2CH3 C-H C-Br 1
B9.020 CH2CH3 C-H C-Cl 1
B9.021 CH2CH3 C-H C-H 2
B9.022 CH2CH3 C-H C-CF3 2
B9.023 CH2CH3 C-H C-Br 2
B9.024 CH2CH3 C-H C-Cl 2
B9.025 CH3 C-H N 0
B9.026 CH3 C-H N 1
B9.027 CH3 C-H N 2
B9.028 CH2CH3 C-H N 0
B9.029 CH2CH3 C-H N 1
B9.030 CH2CH3 C-H N 2
Table J：With chemical formula B10Group
Group R3 V9 V10 V11 m
B10.001 CH2CH3 C-H C-H C-H 0
B10.002 CH2CH3 C-H C-H C-H 1
B10.003 CH2CH3 C-H C-H C-H 2
B10.004 CH2CH3 N C-H C-H 0
B10.005 CH2CH3 N C-H C-H 1
B10.006 CH2CH3 N C-H C-H 2
B10.007 CH2CH3 N C-H N 0
B10.008 CH2CH3 N C-H N 1
B10.009 CH2CH3 N C-H N 2
B10.010 CH2CH3 N N N 0
B10.011 CH2CH3 N N N 1
B10.012 CH2CH3 N N N 2
Table K：With chemical formula B11Group
Table L：With chemical formula A1Group
Table M：With chemical formula A2Group
Table N：With chemical formula A3Group
Group R1 R2 G1 G2 G4
A3.001 CH3 H C-H C-H N
A3.002 CF3 H C-H C-H N
A3.003 Cl H C-H C-H N
A3.004 Br H C-H C-H N
A3.005 CH3 H C-H N N
A3.006 CF3 H C-H N N
A3.007 Cl H C-H N N
A3.008 Br H C-H N N
A3.009 CH3 H N N N
A3.010 CF3 H N N N
A3.011 Cl H N N N
A3.012 Br H N N N
A3.013 CH3 H C-H C-H C-CH3
A3.014 CF3 H C-H C-H C-CH3
A3.015 Cl H C-H C-H C-CH3
A3.016 Br H C-H C-H C-CH3
A3.017 CH3 H C-H N C-CH3
A3.018 CF3 H C-H N C-CH3
A3.019 Cl H C-H N C-CH3
A3.020 Br H C-H N C-CH3
A3.021 CH3 H N N C-CH3
A3.022 CF3 H N N C-CH3
A3.023 Cl H N N C-CH3
A3.024 Br H N N C-CH3
Table O：With chemical formula A4Group
Table P：With chemical formula A4Group
Group R1 R2 G1 G2 G5 G4
A5.001 CH3 H C-H C-H N N
A5.002 CF3 H C-H C-H N N
A5.003 Cl H C-H C-H N N
A5.004 Br H C-H C-H N N
A5.005 CH3 H C-H N N N
A5.006 CF3 H C-H N N N
A5.007 Cl H C-H N N N
A5.008 Br H C-H N N N
A5.009 CH3 H C-H C-H C-CH3 N
A5.010 CF3 H C-H C-H C-CH3 N
A5.011 Cl H C-H C-H C-CH3 N
A5.012 Br H C-H C-H C-CH3 N
A5.013 CH3 H C-H N C-CH3 N
A5.014 CF3 H C-H N C-CH3 N
A5.015 Cl H C-H N C-CH3 N
A5.016 Br H C-H N C-CH3 N
Table Q：With chemical formula A6Group
Table R：With chemical formula A7aGroup
Group R1 G1 G2 G3
A7.001 CH3 C-H C-H C-CH3
A7.002 CF3 C-H C-H C-CH3
A7.003 Cl C-H C-H C-CH3
A7.004 Br C-H C-H C-CH3
A7.005 CH3 C-H C-H C-H
A7.006 CF3 C-H C-H C-H
A7.007 Cl C-H C-H C-H
A7.008 Br C-H C-H C-H
A7.009 CH3 C-H C-H N
A7.010 CF3 C-H C-H N
A7.011 Cl C-H C-H N
A7.012 Br C-H C-H N
Table S：With chemical formula A8aGroup
Group R1 G1 G2 G4
A8.001 CH3 C-H C-H C-H
A8.002 CF3 C-H C-H C-H
A8.003 Cl C-H C-H C-H
A8.004 Br C-H C-H C-H
A8.005 CH3 C-H C-H C-CH3
A8.006 CF3 C-H C-H C-CH3
A8.007 Cl C-H C-H C-CH3
A8.008 Br C-H C-H C-CH3
A8.009 CH3 C-H C-H N
A8.010 CF3 C-H C-H N
A8.011 Cl C-H C-H N
A8.012 Br C-H C-H N
Table 1：The table discloses 66 kinds of compounds with chemical formula A1.014-B1, and wherein group B1 is shown in Table A Group B1.049-B1.084 and B1.091-B1.120, and A1.014 defined in table L.
Table 2：The table discloses 66 kinds of compounds with chemical formula A1.018-B1, and wherein group B1 is shown in Table A Group B1.049-B1.084 and B1.091-B1.120, and A1.018 defined in table L.
Table 3：The table discloses 66 kinds of compounds with chemical formula A1.022-B1, and wherein group B1 is shown in Table A Group B1.049-B1.084 and B1.091-B1.120, and A1.022 defined in table L.
Table 4：The table discloses 36 kinds of compounds with chemical formula A1.014-B2, and wherein group B2 is shown in table B Group B2.001-B2.036, and A1.014 defined in table L.
Table 5：The table discloses 36 kinds of compounds with chemical formula A1.018-B2, and wherein group B2 is shown in table B Group B2.001-B2.036, and A1.018 defined in table L.
Table 6：The table discloses 36 kinds of compounds with chemical formula A1.022-B2, and wherein group B2 is shown in table B Group B2.001-B2.036, and A1.022 defined in table L.
Table 7：The table discloses 24 kinds of compounds with chemical formula A1.014-B3, and wherein group B3 is shown in table C Group B3.001-B3.024, and A1.014 defined in table L.
Table 8：The table discloses 24 kinds of compounds with chemical formula A1.018-B3, and wherein group B3 is shown in table C Group B3.001-B3.024, and A1.018 defined in table L.
Table 9：The table discloses 24 kinds of compounds with chemical formula A1.022-B3, and wherein group B3 is shown in table C Group B3.001-B3.024, and A1.022 defined in table L.
Table 10：The table discloses 8 kinds of compounds with chemical formula A1.014-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A1.014 defined in table L.
Table 11：The table discloses 8 kinds of compounds with chemical formula A1.018-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A1.018 defined in table L.
Table 12：The table discloses 8 kinds of compounds with chemical formula A1.022-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A1.022 defined in table L.
Table 13：The table discloses 24 kinds of compounds with chemical formula A1.014-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A1.014 defined in table L.
Table 14：The table discloses 24 kinds of compounds with chemical formula A1.018-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A1.018 defined in table L.
Table 15：The table discloses 24 kinds of compounds with chemical formula A1.022-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A1.022 defined in table L.
Table 16：The table discloses 16 kinds of compounds with chemical formula A1.014-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A1.014 defined in table L.
Table 17：The table discloses 16 kinds of compounds with chemical formula A1.018-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A1.018 defined in table L.
Table 18：The table discloses 16 kinds of compounds with chemical formula A1.022-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A1.022 defined in table L.
Table 19：The table discloses 54 kinds of compounds with chemical formula A1.014-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A1.014 defined in table L.
Table 20：The table discloses 54 kinds of compounds with chemical formula A1.018-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A1.018 defined in table L.
Table 21：The table discloses 54 kinds of compounds with chemical formula A1.022-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A1.022 defined in table L.
Table 22：The table discloses 12 kinds of compounds with chemical formula A1.014-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A1.014 defined in table L.
Table 23：The table discloses 12 kinds of compounds with chemical formula A1.018-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A1.018 defined in table L.
Table 24：The table discloses 12 kinds of compounds with chemical formula A1.022-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A1.022 defined in table L.
Table 25：The table discloses 30 kinds of compounds with chemical formula A1.014-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A1.014 defined in table L.
Table 26：The table discloses 30 kinds of compounds with chemical formula A1.018-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A1.018 defined in table L.
Table 27：The table discloses 30 kinds of compounds with chemical formula A1.022-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A1.0122 defined in table L.
Table 28：The table discloses 12 kinds of compounds with chemical formula A1.014-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A1.014 defined in table L.
Table 29：The table discloses 12 kinds of compounds with chemical formula A1.018-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A1.018 defined in table L.
Table 30：The table discloses 12 kinds of compounds with chemical formula A1.022-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A1.022 defined in table L.
Table 31：The table discloses 64 kinds of compounds with chemical formula A1.014-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A1.014 defined in table L.
Table 29：The table discloses 64 kinds of compounds with chemical formula A1.018-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A1.018 defined in table L.
Table 30：The table discloses 64 kinds of compounds with chemical formula A1.022-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A1.022 defined in table L.
Table 31：The table discloses 132 kinds of compounds with chemical formula A2.006-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A2.006 defined in table M.
Table 32：The table discloses 132 kinds of compounds with chemical formula A2.018-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A2.018 defined in table M.
Table 33：The table discloses 36 kinds of compounds with chemical formula A2.006-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A2.006 defined in table M.
Table 34：The table discloses 36 kinds of compounds with chemical formula A2.018-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A2.018 defined in table M.
Table 35：The table discloses 24 kinds of compounds with chemical formula A2.006-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A2.0006 defined in table M.
Table 36：The table discloses 24 kinds of compounds with chemical formula A2.018-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A2.018 defined in table M.
Table 37：The table discloses 8 kinds of compounds with chemical formula A2.006-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A2.006 defined in table M.
Table 38：The table discloses 8 kinds of compounds with chemical formula A2.018-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A2.018 defined in table M.
Table 39：The table discloses 24 kinds of compounds with chemical formula A2.006-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A2.006 defined in table M.
Table 40：The table discloses 24 kinds of compounds with chemical formula A2.018-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A2.018 defined in table M.
Table 42：The table discloses 16 kinds of compounds with chemical formula A2.006-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A2.006 defined in table M.
Table 43：The table discloses 16 kinds of compounds with chemical formula A2.018-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A2.018 defined in table M.
Table 44：The table discloses 54 kinds of compounds with chemical formula A2.006-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A2.0106 defined in table M.
Table 45：The table discloses 54 kinds of compounds with chemical formula A2.018-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A2.018 defined in table M.
Table 46：The table discloses 12 kinds of compounds with chemical formula A2.006-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A2.006 defined in table M.
Table 47：The table discloses 12 kinds of compounds with chemical formula A2.018-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A2.018 defined in table M.
Table 48：The table discloses 30 kinds of compounds with chemical formula A2.006-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A2.006 defined in table M.
Table 49：The table discloses 30 kinds of compounds with chemical formula A2.018-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A2.018 defined in table M.
Table 50：The table discloses 12 kinds of compounds with chemical formula A2.006-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A2.006 defined in table M.
Table 51：The table discloses 12 kinds of compounds with chemical formula A2.018-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A2.018 defined in table M.
Table 52：The table discloses 64 kinds of compounds with chemical formula A2.006-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A2.006 defined in table M.
Table 53：The table discloses 64 kinds of compounds with chemical formula A2.018-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A2.018 defined in table M.
Table 54：The table discloses 132 kinds of compounds with chemical formula A3.006-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A3.006 defined in table N.
Table 55：The table discloses 132 kinds of compounds with chemical formula A3.018-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A3.018 defined in table N.
Table 56：The table discloses 36 kinds of compounds with chemical formula A3.006-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A3.006 defined in table N.
Table 57：The table discloses 36 kinds of compounds with chemical formula A3.018-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A3.018 defined in table N.
Table 58：The table discloses 24 kinds of compounds with chemical formula A3.006-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A3.006 defined in table N.
Table 59：The table discloses 24 kinds of compounds with chemical formula A3.018-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A3.018 defined in table N.
Table 60：The table discloses 8 kinds of compounds with chemical formula A3.006-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A3.006 defined in table N.
Table 61：The table discloses 8 kinds of compounds with chemical formula A3.018-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A3.018 defined in table N.
Table 62：The table discloses 24 kinds of compounds with chemical formula A3.006-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A3.006 defined in table N.
Table 63：The table discloses 24 kinds of compounds with chemical formula A3.018-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A3.018 defined in table N.
Table 64：The table discloses 16 kinds of compounds with chemical formula A3.006-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A3.006 defined in table N.
Table 65：The table discloses 16 kinds of compounds with chemical formula A3.018-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A3.018 defined in table N.
Table 66：The table discloses 54 kinds of compounds with chemical formula A3.006-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A3.006 defined in table N.
Table 67：The table discloses 54 kinds of compounds with chemical formula A3.018-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A3.018 defined in table N.
Table 68：The table discloses 12 kinds of compounds with chemical formula A3.006-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A3.006 defined in table N.
Table 69：The table discloses 12 kinds of compounds with chemical formula A3.0018-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A3.018 defined in table N.
Table 70：The table discloses 30 kinds of compounds with chemical formula A3.006-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A3.006 defined in table N.
Table 71：The table discloses 30 kinds of compounds with chemical formula A3.018-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A3.018 defined in table N.
Table 72：The table discloses 12 kinds of compounds with chemical formula A3.006-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A3.006 defined in table N.
Table 73：The table discloses 12 kinds of compounds with chemical formula A3.018-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A3.018 defined in table N.
Table 74：The table discloses 64 kinds of compounds with chemical formula A3.006-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A3.006 defined in table N.
Table 75：The table discloses 64 kinds of compounds with chemical formula A3.018-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A3.018 defined in table N.
Table 76：The table discloses 132 kinds of compounds with chemical formula A4.006-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A4.006 defined in table O.
Table 77：The table discloses 132 kinds of compounds with chemical formula A4.008-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A4.008 defined in table O.
Table 78：The table discloses 36 kinds of compounds with chemical formula A4.006-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A4.006 defined in table O.
Table 79：The table discloses 36 kinds of compounds with chemical formula A4.008-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A4.008 defined in table O.
Table 80：The table discloses 24 kinds of compounds with chemical formula A4.006-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A4.006 defined in table O.
Table 81：The table discloses 24 kinds of compounds with chemical formula A4.008-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A4.008 defined in table O.
Table 82：The table discloses 8 kinds of compounds with chemical formula A4.006-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A4.006 defined in table O.
Table 83：The table discloses 8 kinds of compounds with chemical formula A4.008-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A4.008 defined in table O.
Table 84：The table discloses 24 kinds of compounds with chemical formula A4.006-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A4.006 defined in table O.
Table 85：The table discloses 24 kinds of compounds with chemical formula A4.008-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A4.008 defined in table O.
Table 86：The table discloses 16 kinds of compounds with chemical formula A4.006-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A4.006 defined in table O.
Table 87：The table discloses 16 kinds of compounds with chemical formula A4.008-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A4.008 defined in table O.
Table 88：The table discloses 54 kinds of compounds with chemical formula A4.006-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A4.006 defined in table O.
Table 89：The table discloses 54 kinds of compounds with chemical formula A4.008-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A4.008 defined in table O.
Table 90：The table discloses 12 kinds of compounds with chemical formula A4.006-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A4.006 defined in table O.
Table 91：The table discloses 12 kinds of compounds with chemical formula A4.008-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A4.008 defined in table O.
Table 92：The table discloses 30 kinds of compounds with chemical formula A4.006-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A4.006 defined in table O.
Table 93：The table discloses 30 kinds of compounds with chemical formula A4.008-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A4.008 defined in table O.
Table 94：The table discloses 12 kinds of compounds with chemical formula A4.006-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A4.006 defined in table O.
Table 95：The table discloses 12 kinds of compounds with chemical formula A4.008-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A4.008 defined in table O.
Table 96：The table discloses 64 kinds of compounds with chemical formula A4.006-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A4.006 defined in table O.
Table 97：The table discloses 64 kinds of compounds with chemical formula A4.008-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A3.008 defined in table O.
Table 98：The table discloses 132 kinds of compounds with chemical formula A5.006-B1, and wherein group B1 is shown in Table A Group B1.001-B1.132, and A5.006 defined in table P.
Table 99：The table discloses 36 kinds of compounds with chemical formula A5.006-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A5.006 defined in table P.
Table 100：The table discloses 24 kinds of compounds with chemical formula A5.006-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A5.006 defined in table P.
Table 101：The table discloses 8 kinds of compounds with chemical formula A5.006-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A4.006 defined in table P.
Table 102：The table discloses 24 kinds of compounds with chemical formula A5.006-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A5.006 defined in table P.
Table 103：The table discloses 16 kinds of compounds with chemical formula A5.006-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A5.006 defined in table P.
Table 104：The table discloses 54 kinds of compounds with chemical formula A5.006-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A5.006 defined in table P.
Table 105：The table discloses 12 kinds of compounds with chemical formula A5.006-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A5.006 defined in table P.
Table 106：The table discloses 30 kinds of compounds with chemical formula A5.006-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A5.006 defined in table P.
Table 107：The table discloses 12 kinds of compounds with chemical formula A5.006-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A5.006 defined in table P.
Table 108：The table discloses 64 kinds of compounds with chemical formula A5.006-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A5.006 defined in table P.
Table 109：The table discloses 132 kinds of compounds with chemical formula A6.002-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A6.002 defined in table Q.
Table 110：The table discloses 132 kinds of compounds with chemical formula A6.014-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A6.014 defined in table Q.
Table 111：The table discloses 36 kinds of compounds with chemical formula A6.002-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A6.002 defined in table Q.
Table 112：The table discloses 36 kinds of compounds with chemical formula A6.014-B2, and wherein group B2 is shown in table B Group B2.001-B2.0036, and A6.014 defined in table Q.
Table 113：The table discloses 24 kinds of compounds with chemical formula A6.002-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A6.002 defined in table Q.
Table 114：The table discloses 24 kinds of compounds with chemical formula A6.014-B3, and wherein group B3 is shown in table C Group B3.001-B3.0024, and A6.014 defined in table Q.
Table 115：The table discloses 8 kinds of compounds with chemical formula A6.002-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A6.002 defined in table Q.
Table 116：The table discloses 8 kinds of compounds with chemical formula A6.014-B4, and wherein group B4 is shown in table D Group B4.001-B4.008, and A6.014 defined in table Q.
Table 117：The table discloses 24 kinds of compounds with chemical formula A6.002-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A6.002 defined in table Q.
Table 118：The table discloses 24 kinds of compounds with chemical formula A6.014-B5, and wherein group B5 is shown in table E Group B5.001-B5.024, and A4.014 defined in table Q.
Table 119：The table discloses 16 kinds of compounds with chemical formula A6.002-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A6.002 defined in table Q.
Table 120：The table discloses 16 kinds of compounds with chemical formula A6.014-B6, and wherein group B6 is shown in table F Group B6.001-B6.016, and A6.014 defined in table Q.
Table 121：The table discloses 54 kinds of compounds with chemical formula A6.002-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A6.002 defined in table Q.
Table 122：The table discloses 54 kinds of compounds with chemical formula A6.014-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A6.014 defined in table Q.
Table 123：The table discloses 12 kinds of compounds with chemical formula A6.002-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A6.002 defined in table Q.
Table 124：The table discloses 12 kinds of compounds with chemical formula A6.0014-B8, and wherein group B8 is shown in table H The group B8.001-B8.012 that goes out, and A6.014 defined in table Q.
Table 125：The table discloses 30 kinds of compounds with chemical formula A6.002-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A6.002 defined in table Q.
Table 126：The table discloses 30 kinds of compounds with chemical formula A6.014-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A6.014 defined in table Q.
Table 127：The table discloses 12 kinds of compounds with chemical formula A6.002-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A6.002 defined in table Q.
Table 128：The table discloses 12 kinds of compounds with chemical formula A6.014-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A6.014 defined in table Q.
Table 129：The table discloses 64 kinds of compounds with chemical formula A6.002-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A6.002 defined in table Q.
Table 130：The table discloses 64 kinds of compounds with chemical formula A6.014-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A6.014 defined in table Q.
Table 131：The table discloses 132 kinds of compounds with chemical formula A7.002-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A7.002 defined in table R.
Table 132：The table discloses 132 kinds of compounds with chemical formula A7.006-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A7.006 defined in table R.
Table 133：The table discloses 132 kinds of compounds with chemical formula A7.010-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A7.010 defined in table R.
Table 134：The table discloses 54 kinds of compounds with chemical formula A7.002-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A7.002 defined in table R.
Table 135：The table discloses 54 kinds of compounds with chemical formula A7.006-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A7.006 defined in table R.
Table 136：The table discloses 54 kinds of compounds with chemical formula A7.010-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A7.010 defined in table R.
Table 137：The table discloses 12 kinds of compounds with chemical formula A7.002-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A7.002 defined in table R.
Table 138：The table discloses 12 kinds of compounds with chemical formula A7.006-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A7.006 defined in table R.
Table 139：The table discloses 12 kinds of compounds with chemical formula A7.010-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A7.010 defined in table R.
Table 140：The table discloses 30 kinds of compounds with chemical formula A7.002-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A7.002 defined in table R.
Table 142：The table discloses 30 kinds of compounds with chemical formula A7.006-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A7.006 defined in table R.
Table 143：The table discloses 30 kinds of compounds with chemical formula A7.010-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A7.010 defined in table R.
Table 144：The table discloses 12 kinds of compounds with chemical formula A7.002-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A7.002 defined in table R.
Table 145：The table discloses 12 kinds of compounds with chemical formula A7.006-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A7.006 defined in table R.
Table 146：The table discloses 12 kinds of compounds with chemical formula A7.010-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A7.010 defined in table R.
Table 147：The table discloses 64 kinds of compounds with chemical formula A7.002-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A7.002 defined in table R.
Table 148：The table discloses 64 kinds of compounds with chemical formula A7.006-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A7.006 defined in table R.
Table 149：The table discloses 64 kinds of compounds with chemical formula A7.010-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A7.010 defined in table R.
Table 150：The table discloses 132 kinds of compounds with chemical formula A8.002-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A8.002 defined in table R.
Table 151：The table discloses 132 kinds of compounds with chemical formula A8.006-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A8.006 defined in table S.
Table 152：The table discloses 132 kinds of compounds with chemical formula A8.010-B1, and wherein group B1 is shown in Table A The group B1.001-B1.132 that goes out, and A8.010 defined in table S.
Table 153：The table discloses 54 kinds of compounds with chemical formula A8.002-B7, and wherein group B7 is shown in table G Group B7.001-B7.054, and A8.002 defined in table S.
Table 154：The table discloses 54 kinds of compounds with chemical formula A8.006-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A8.006 defined in table R.
Table 155：The table discloses 54 kinds of compounds with chemical formula A8.010-B7, and wherein B7 is the base shown in table G Group B7.001-B7.054, and A8.010 defined in table R.
Table 156：The table discloses 12 kinds of compounds with chemical formula A8.002-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A8.002 defined in table S.
Table 157：The table discloses 12 kinds of compounds with chemical formula A8.006-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A8.006 defined in table S.
Table 158：The table discloses 12 kinds of compounds with chemical formula A8.010-B8, and wherein group B8 is shown in table H Group B8.001-B8.012, and A8.010 defined in table S.
Table 159：The table discloses 30 kinds of compounds with chemical formula A8.002-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A8.002 defined in table S.
Table 160：The table discloses 30 kinds of compounds with chemical formula A4.006-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A8.006 defined in table S.
Table 161：The table discloses 30 kinds of compounds with chemical formula A8.010-B9, and wherein group B9 is shown in Table I Group B9.001-B9.030, and A8.010 defined in table S.
Table 162：The table discloses 12 kinds of compounds with chemical formula A8.002-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A8.002 defined in table S.
Table 164：The table discloses 12 kinds of compounds with chemical formula A8.006-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A8.006 defined in table S.
Table 165：The table discloses 12 kinds of compounds with chemical formula A8.010-B10, and wherein group B10 is shown in table J The group B10.001-B10.012 that goes out, and A8.010 defined in table S.
Table 166：The table discloses 64 kinds of compounds with chemical formula A8.002-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A8.002 defined in table S.
Table 167：The table discloses 64 kinds of compounds with chemical formula A8.006-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A8.006 defined in table S.
Table 168：The table discloses 64 kinds of compounds with chemical formula A8.010-B11, and wherein group B11 is shown in table K The group B11.001-B11.064 that goes out, and A8.010 defined in table S.
Table T：The physicochemical data of compound with Formula I：
Table U：The physicochemical data of especially preferred compound and its intermediate with Formula I：
One group of compound with Formula I is preferably provided, as defined in embodiments illustrated below (1) to (7)：
According to the present invention one group of especially preferred compound with Formula I be as defined in embodiment (1), and Including following combination
(1)：Group A2 and group B, B are selected from B7, B9 and B11；
Wherein A2 is preferably what is represented by group A2.1
Wherein R40It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4 Haloalkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
G21It is nitrogen, CH, C-C1-C6Alkyl, C-C1-C6Haloalkyl, C- halogens, C-CN, C-O-C1-C4Alkyl, C-S-C1- C4Alkyl, C-SO2-C1-C4Alkyl, C-S- phenyl, C-SO2- phenyl or C-SO2-C1-C4Haloalkyl；And
G51It is nitrogen, CH, C-C1-C6Alkyl, C-C1-C6Haloalkyl, C- halogens, C-CN, C-O-C1-C4Alkyl, C-S-C1- C4Alkyl, C-SO2-C1-C4Alkyl, C-S- phenyl, C-SO2- phenyl or C-SO2-C1-C4Haloalkyl；And group B7, B9 and B11 is preferably to be represented by the group selected from B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Especially preferred compound according to embodiment (1) is represented by embodiment (1.1), wherein
(1.1), in group A2.1
R40It is C1-C4Haloalkyl, particularly trifluoromethyl；
G21It is nitrogen or CH；And
G51It is nitrogen or C-C1-C6Alkyl, particularly nitrogen or C- methyl；
And in group B7.1, B9.1 and B11.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, preferably ethyl；And
R42It is C1-C4Haloalkyl, preferably trifluoromethyl；
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, preferably ethyl；And
R44It is C1-C4Haloalkyl, preferably trifluoromethyl；
M is 2；
R45It is C1-C4Alkyl, preferably ethyl；And
R46It is C1-C4Haloalkyl, preferably trifluoromethyl.
According to the present invention another group of especially preferred compound with Formula I be as defined in embodiment (2), And including following combination
(2)：Group A3 and group B, B are selected from B7, B9 and B11；
Wherein A3 is preferably what is represented by group A3.1
Wherein R47It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4 Haloalkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
G41It is nitrogen, CH, C-C1-C6Alkyl, C-C1-C6Haloalkyl, C- halogens, C-CN, C-O-C1-C4Alkyl, C-S-C1- C4Alkyl, C-SO2-C1-C4Alkyl, C-S- phenyl, C-SO2- phenyl or C-SO2-C1-C4Haloalkyl；And
G22It is nitrogen, CH, C-C1-C6Alkyl, C-C1-C6Haloalkyl, C- halogens, C-CN, C-O-C1-C4Alkyl, C-S-C1- C4Alkyl, C-SO2-C1-C4Alkyl, C-S- phenyl, C-SO2- phenyl or C-SO2-C1-C4Haloalkyl；And group B7, B9 and B11 is preferably to be represented by the group selected from B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Especially preferred compound according to embodiment (2) is represented by embodiment (2.1), wherein
(2.1), in group A3.1
R47It is C1-C4Haloalkyl, particularly trifluoromethyl；
G22It is nitrogen or CH；And
G41It is nitrogen or C-C1-C6Alkyl, particularly nitrogen or C- methyl；
And in group B7.1, B9.1 and B11.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, preferably ethyl；And
R42It is C1-C4Haloalkyl, preferably trifluoromethyl；
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, preferably ethyl；And
R44It is C1-C4Haloalkyl, preferably trifluoromethyl；
M is 2；
R45It is C1-C4Alkyl, preferably ethyl；And
R46It is C1-C4Haloalkyl, preferably trifluoromethyl.
According to the present invention another group of especially preferred compound with Formula I be as defined in embodiment (3), And including following combination
(3)：Group A4 and group B1；
Wherein A4 is preferably what is represented by group A4.1
Wherein R48It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4 Haloalkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
J3It is sulphur oxygen or N- methyl；And
R49It is hydrogen, C1-C6Alkyl, C1-C6Haloalkyl, halogen, CN, O-C1-C4Alkyl, S-C1-C4Alkyl, SO2-C1-C4 Alkyl, S- phenyl, SO2- phenyl or SO2-C1-C4Haloalkyl；
And group B1 is
Wherein m is 0,1 or 2；
R51It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R50It is hydrogen, C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl- C1-C4Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Preferred compound according to embodiment (3) is also to be represented by embodiment (3.1), wherein
(3.1), in group A4.1
R48It is C1-C4Haloalkyl, particularly trifluoromethyl；
J3It is oxygen, sulphur or N- methyl；And
G49It is hydrogen or C1-C6Alkyl, particularly hydrogen or methyl；
And group B1, B7, B9 and B11 are preferably what is represented by the group selected from B1.1, B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
R51It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R50It is hydrogen, C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl- C1-C4Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Other especially preferred compound according to embodiment (3) is represented by embodiment (3.2), wherein (3.2), In group A4.1
R48It is C1-C4Haloalkyl, particularly trifluoromethyl；
J3It is oxygen, sulphur or N- methyl；And
G49It is hydrogen or C1-C6Alkyl, particularly hydrogen or methyl；
And in group B1.1
M is 2；
V11It is nitrogen or methine；
R51It is C1-C4Alkyl, preferably ethyl；And
R50It is hydrogen or C1-C4Haloalkyl, preferably hydrogen or trifluoromethyl.
According to the present invention another group of especially preferred compound with Formula I be as defined in embodiment (4), And including following combination
(4)：Group A5 and group B, B are selected from B1, B7, B9 and B11；
Wherein A5 is preferably what is represented by group A5.1
Wherein
G55It is nitrogen or C-R53；
R53It is C1-C4Alkyl；
G25It is nitrogen or methine；And
R52It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4Halo Alkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
And group B1, B7, B9 and B11 are preferably what is represented by the group selected from B1.1, B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
R51It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R50It is hydrogen, C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl- C1-C4Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Especially preferred compound according to embodiment (4) is represented by embodiment (4.1), wherein
(4.1), in group A5.1
R52It is C1-C4Haloalkyl, particularly trifluoromethyl；
G55It is nitrogen or C-C1-C4Alkyl, preferably nitrogen or methyl；And
G25It is nitrogen or methine；
And in group B1.1
M is 2；
V11It is nitrogen or methine；
R51It is C1-C4Alkyl, preferably ethyl；And
R50It is hydrogen or C1-C4Haloalkyl, preferably hydrogen or trifluoromethyl；
In group B7.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, preferably ethyl；And
R42It is C1-C4Haloalkyl, preferably trifluoromethyl；
In group B9.1
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, preferably ethyl；And
R44It is C1-C4Haloalkyl, preferably trifluoromethyl；
And in group B11.1
M is 2；
R45It is C1-C4Alkyl, preferably ethyl；And
R46It is C1-C4Haloalkyl, preferably trifluoromethyl.
According to the present invention another group of particularly preferred compound with Formula I be as defined in embodiment (5), And including following combination
(5)：Group A6 and group B, B are selected from B1, B7, B9 and B11；
Wherein A6 is preferably what is represented by group A6.1
Wherein
G36It is N-R55, oxygen or sulphur；
R55It is C1-C4Alkyl；
G26It is nitrogen or methine；And
R54It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4Halo Alkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
And group B1, B7, B9 and B11 are preferably what is represented by the group selected from B1.1, B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
R51It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R50It is hydrogen, C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl- C1-C4Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Especially preferred compound according to embodiment (5) is represented by embodiment (5.1), wherein
(5.1), in group A6.1
R54It is C1-C4Haloalkyl, particularly trifluoromethyl；
G36It is N-C1-C4Alkyl, oxygen or sulphur；It is preferred that N-CH3, oxygen or sulphur；And
G26It is nitrogen or methine；
And in group B1.1
M is 2；
V11It is nitrogen or methine；
R51It is C1-C4Alkyl, preferably ethyl；And
R50It is hydrogen or C1-C4Haloalkyl, preferably hydrogen or trifluoromethyl；
In group B7.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, preferably ethyl；And
R42It is C1-C4Haloalkyl, preferably trifluoromethyl；
In group B9.1
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, preferably ethyl；And
R44It is C1-C4Haloalkyl, preferably trifluoromethyl；
And in group B11.1
M is 2；
R45It is C1-C4Alkyl, preferably ethyl；And
R46It is C1-C4Haloalkyl, preferably trifluoromethyl.
According to the present invention another group of especially preferred compound with Formula I be as defined in embodiment (6), And including following combination
(6)：Group A7 and group B, B are selected from B1, B7, B9 and B11；
Wherein A7 is preferably what is represented by group A7.1
Wherein
G57It is nitrogen or C-R57；
R57It is hydrogen or C1-C4Alkyl；And
R56It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4Halo Alkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
And group B1, B7, B9 and B11 are preferably what is represented by the group selected from B1.1, B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
R51It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R50It is hydrogen, C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl- C1-C4Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V82It is nitrogen methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Especially preferred compound according to embodiment (6) is represented by embodiment (6.1), wherein
(6.1), in group A7.1
R56It is C1-C4Haloalkyl, particularly trifluoromethyl；And
G57It is nitrogen, C-H or C-C1-C4Alkyl；It is preferred that nitrogen, C-H or C-CH3；
And in group B1.1
M is 2；
V11It is nitrogen or methine；
R51It is C1-C4Alkyl, preferably ethyl；And
R50It is hydrogen or C1-C4Haloalkyl, preferably hydrogen or trifluoromethyl；
In group B7.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, preferably ethyl；And
R42It is C1-C4Haloalkyl, preferably trifluoromethyl；
In group B9.1
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, preferably ethyl；And
R44It is C1-C4Haloalkyl, preferably trifluoromethyl；
And in group B11.1
M is 2；
R45It is C1-C4Alkyl, preferably ethyl；And
R46It is C1-C4Haloalkyl, preferably trifluoromethyl.
According to the present invention another group of especially preferred compound with Formula I be as defined in embodiment (7), And including following combination
(7)：Group A8 and group B, B are selected from B1, B7, B9 and B11；
Wherein A8 is preferably represented by group A8.1
Wherein
G48It is nitrogen or C-R59；
R59It is hydrogen or C1-C4Alkyl；And
R58It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4Halo Alkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
And group B1, B7, B9 and B11 are preferably what is represented by the group selected from B1.1, B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
R51It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R50It is hydrogen, C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl- C1-C4Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo ring Alkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4 Alkyl, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl.
Especially preferred compound according to embodiment (7) is represented by embodiment (7.1), wherein
(7.1), in group A8.1
R58It is C1-C4Haloalkyl, particularly trifluoromethyl；And
G48It is nitrogen, C-H or C-C1-C4Alkyl；It is preferred that nitrogen, C-H or C-CH3；
And in group B1.1
M is 2；
V11It is nitrogen or methine；
R51It is C1-C4Alkyl, preferably ethyl；And
R50It is hydrogen or C1-C4Haloalkyl, preferably hydrogen or trifluoromethyl；
In group B7.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, preferably ethyl；And
R42It is C1-C4Haloalkyl, preferably trifluoromethyl；
In group B9.1
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, preferably ethyl；And
R44It is C1-C4Haloalkyl, preferably trifluoromethyl；
And in group B11.1
M is 2；
R45It is C1-C4Alkyl, preferably ethyl；And
R46It is C1-C4Haloalkyl, preferably trifluoromethyl.
The especially preferred compound with Formula I of the present invention is listed in following table V1 into V26.Table V 1 is to V26 Represent the further embodiment of the present invention：In these tables, Et is CH2CH3, Me is CH3, NMe is N-CH3, and CMe is C-Me etc..
Table V 1：Compound with chemical formula A2.1-B7.1：
Table V 2：Compound with chemical formula A2.1-B9.1：
Table V 3：Compound with chemical formula A2.1-B11.1：
Table V 4：Compound with chemical formula A3.1-B7.1：
TableV5：Compound with chemical formula A3.1-B9.1：
TableV6：Compound with chemical formula A3.1-B11.1：
Table V 7：Compound with chemical formula A4.1-B1.1：
Table V 8：Compound with chemical formula A5.1-B1.1：
Table V 9：Compound with chemical formula A5.1-B7.1：
Table V 10：Compound with chemical formula A5.1-B9.1：
TableV11：Compound with chemical formula A5.1-B11.1：
Table V 12：Compound with chemical formula A6.1-B1.1：
Table V 13：Compound with chemical formula A6.1-B7.1：
Table V 14：Compound with chemical formula A6.1-B9.1：
Table V 15：Compound with chemical formula A6.1-B11.1：
Table V 16：Compound with chemical formula A7.1-B1.1：
Table V 17：Compound with chemical formula A7.1-B7.1：
Table V 18：Compound with chemical formula A7.1-B9.1：
Table V 19：Compound with chemical formula A7.1-B11.1：
Table V 20：Compound with chemical formula A8.1-B1.1：
Table V 21：Compound with chemical formula A8.1-B7.1：
Table V 22：Compound with chemical formula A8.1-B9.1：
TableV23：Compound with chemical formula A8.1-B11.1：
Table V 24：Compound with chemical formula A4.1-B7.1：
Table V 25：Compound with chemical formula A4.1-B9.1：
Table V 26：Compound with chemical formula A4.1-B11.1：
Preparation example (%=percentage by weights)
The emulsion of any desired concentration can be prepared from these concentrates by being diluted with water.
These solution are adapted to use in the form of droplet.
The active component is dissolved in dichloromethane, the solution is sprayed on one or more carriers and then will Solvent is evaporated under vacuo.
Instant dirt agent is obtained by the way that carrier is mixed closely with active component.
Active component is mixed with additive and fully grinds the mixture in a suitable grinder.This gives Wettable powder is gone out, these wettable powders can be diluted with water to provide the suspension of arbitrary desired concentration Liquid.
Example F6：Extruder particle
The active component is mixed with these additives, and grinds the mixture, is moistened with water, extrude, be granulated and Dried in air stream.
Example F7：The particle of coating
Active component 3%
Polyethylene glycol (MW 200) 3%
Kaolin 94%
In a blender, the active component of this fine gtinding is uniformly applied to be moistened with polyethylene glycol Kaolin on.These give dustless coated granule.
Example F8：Suspension-concentrates
The active component of the fine gtinding is mixed closely with these additives.Any suspension for wishing concentration can Prepared from the suspension-concentrates so obtained by being diluted with water.
The combination is sufficiently mixed with these adjuvants and is fully ground mixture in an appropriate grinder, from And obtain the powder for being used directly for seed treatment.
Example F10：Emulsifiable concentrate
The emulsion with any required dilution that can be used in plant protection can be by being diluted with water from this Obtained in kind concentrate.
Example F11：Flowable concentrate for seed treatment
The combination of this fine dispersion is closely mixed with these adjuvants, so as to give a kind of suspension-concentrates, It can make to be diluted with water from the concentrate and obtain any desired suspension., can be to plant living using such dilution body Handled together with plant propagation material and it is protected for microbial infection by spraying, toppling over or impregnate.
There is the composition for killing insect, mite killing and/or Fungicidally active by adding other, according to these compositions of the present invention Activity can significantly widen, and be suitable for environment at that time.Compound with Formula I is with other with killing elder brother The mixture of the composition of worm, mite killing and/or Fungicidally active can also have further, it is unexpected the advantages of, these are excellent Point can also be described as synergistic activity in broader implication.For example, plant is to its more preferable tolerance, the plant poison reduced Property, insect can be controlled either in their production period (for example, grinding or mixing in their different developmental phases During conjunction, during their storage or their use) more preferable behavior.
Herein, the additive of suitable active component is, for example, the representative thing of the active component of classification below：It is organic Phosphorus compound, nitrophenol derivative, thiocarbamide, juvenile hormone, carbonamidine, benzophenone derivates, ureas, azole derivatives, ammonia Carbamate, pyrethroid, chlorinated hydrocabon, acylureas, pyridylmethylene amino derivative, macrolides, anabasine with And sporeine preparation.
The mixture of the compound with Formula I and active component is that preferably (abbreviation " TX ", which is meant, " to be selected from down below Group a kind of compound, the group by be described in the present invention table 1 to 168 and V1 to V26 in compound group into ")：
A kind of adjuvant, the adjuvant are selected from the group by following material composition：Oil (substitutes title (628)+TX),
A kind of acaricide, the acaricide are selected from the group by following material composition：Acequinocyl ([57960-19-7] [CCN])+ TX, fenpyroximate [134098-61-6] [CCN]+TX, flucythrinate [70124-77-5] [CCN]+TX, 1,1- bis- (4- chlorphenyls)- Cellosolvo (IUPAC titles) (910)+TX, Hexythiazox [78587-05-0] [CCN]+TX, 2,4 dichloro benzene base benzene sulfonic acid Ester (IUPAC/ chemical abstracts name) (1059)+TX, 2- fluoro- N- methyl-N-1- NADs (IUPAC titles) (1295)+TX, 4- Chlorophenyl phenyl sulfone (IUPAC titles) (981)+TX, AVM (1)+TX, acequinocyl (3)+TX, acetyl worm nitrile [CCN]+TX, Acrinathrin (9)+TX, Aldicarb (16)+TX, aldoxycarb (863)+TX, α-cypermethrin (202)+TX, amidithion (870)+ TX, sulfanilamide (SN) mite ester [CCN]+TX, aminothio salt (872)+TX, Citram (875)+TX, Citram binoxalate (875)+TX, Amitraz (24)+TX, aramite (881)+TX, arsenic trioxide (882)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+TX, azinphos ethyl (44)+TX, azinphos-methyl (azinphos-methyl) (45)+TX, azobenzene (IUPAC titles) (888)+TX, azacyclotin (46)+TX, Alamos (889)+TX, benzene mattress spirit (62)+TX, benzene promise sand phosphorus (benoxafos) (replacement title) [CCN]+TX, Citrazon (71)+TX, Ergol (IUPAC titles) [CCN]+TX, connection Phenylhydrazine ester (74)+TX, bifenthrin (76)+TX, binapacryl (907)+TX, brofenxalerate (replacement title)+TX, bromocyclne (bromocyclen) (918)+TX, bromophos (920)+TX, Rilariol (921)+TX, fenisobromolate (94)+TX, Buprofezin (99)+TX, butocarboxim (103)+TX, butanone sulfone prestige (104)+TX, butocarboxim (butylpyridaben) (replacement title)+TX, Lime sulfur (IUPAC titles) (111)+TX, toxaphene (941)+TX, sok (943)+TX, carbaryl (115)+TX, gram Budweiser (118)+TX, carbophenothion (947)+TX, CGA 50 ' 439 (research code) (125)+TX, chinomethionat (chinomethionat) (126)+TX, Neotran (959)+TX, Spanon (964)+TX, chlordimeform-hydrochloride (964)+TX, Chlorfenapyr (130)+TX, chlorfenethol (968)+TX, chlorfenizon (970)+TX, chlorfensulphide (971)+TX, Chlorfenvinphos (131)+TX, ethyl ester Qikron (975)+TX, Yi Tuoming (chloromebuform) (977)+TX, chloromethiuron (978)+TX, Acaralate (983)+ TX, chlopyrifos (145)+TX, chlorpyrifos-methyl (146)+TX, Actellic (994)+TX, cinerin (696)+TX, cinerin 11 (696)+TX, II cinerin II (cinerins) (696)+TX, clofentezine (158)+TX, closantel (replacement title) [CCN]+ TX, Coumafos (174)+TX, Crotamiton (replacement title) [CCN]+TX, crotoxyphos (1010)+TX, cufraneb (1013)+TX, Cyanthoate (1020)+TX, cyflumetofen [400882-07-7]+TX, three lambda-cyhalothrins (196)+TX, plictran (199)+TX, Cypermethrin (201)+TX, DCPM (1032)+TX, DDT (219)+TX, demephion (1037)+TX, demephion-O (1037)+TX, Demephion-S (1037)+TX, demeton (1038)+TX, demeton-methyl (224)+TX, demeton-O (1038)+TX, in methyl It is grand to inhale phosphorus-O (224)+TX, demeton-S (1038)+TX, demeton-methyl-S (224)+TX, demeton-S- methyl sulphurs (demeton-S-methylsulphon) (1039)+TX, methamidophos (226)+TX, dialifos (1042)+TX, diazinon (227)+TX, dichlofluanid (230)+TX, DDVP (236)+TX, BFPO (dicliphos) (replacement title)+TX, open pleasure Dissipate (242)+TX, Carbicron (243)+TX, everywhere gram (1071)+TX, BFPO (dimefox) (1081)+TX, Rogor (262)+ TX, diformazan polynactin (dinactin) (replacement title) (653)+TX, Dinitrocyclohexylphenol (dinex) (1089)+TX, Dinitrocyclohexylphenol (dinex-diclexine) (1089)+TX, dinobuton (dinobuton) (269)+TX, dinocap (dinocap) (270)+TX, Dinocap -4 [CCN]+TX, dinocap -6 [CCN]+TX, dinitro ester (1090)+TX, dinopenton (dinopenton) (1092)+ TX, nitre monooctyl ester (1097)+TX, dinoterbon (1098)+TX, dioxathion (1102)+TX, diphenyl sulphone (DPS) (IUPAC titles) (1103)+ TX, disulfiram (replacement title) [CCN]+TX, disulfoton (278)+TX, DNOC (282)+TX, benzene oxycetylene mite (dofenapyn) (1113)+TX, Doramectin (replacement title) [CCN]+TX, 5a,6,9,9a-hexahydro-6,9-methano-2,4 (294)+TX, endothion (1121)+TX, EPN (297)+ TX, Eprinomectin (replacement title) [CCN]+TX, Ethodan (309)+TX, ethoate methyl (ethoate-methyl) (1134)+ TX, etoxazole (320)+TX, etrimfos (1142)+TX, fenazaflor (1147)+TX, fenazaquin (328)+TX, fenbutatin oxide (330)+TX, fenothiocarb (337)+TX, Fenpropathrin (342)+TX, tebufenpyrad (fenpyrad) (replacement title)+TX, fenpyroximate (345)+TX, fenson (1157)+TX, fluorine nitre diphenylamines (fentrifanil) (1161)+TX, fenvalerate (349)+TX, fluorine Worm nitrile (354)+TX, fluacrypyrim (360)+TX, Fluazuron (1166)+TX, fluorine mite thiophene (1167)+TX, flucycloxuron (366)+TX, fluorine Fenvalerate (367)+TX, Fluenyl (1169)+TX, flufenoxuron (370)+TX, flumethrin (372)+TX, fluoraracide (1174)+TX, taufluvalinate (1184)+TX, FMC 1137 (research code) (1185)+TX, anti-mite amidine (405)+TX, anti-mite Amidine hydrochloride (405)+TX, formothion (1192)+TX, amine first prestige (formparanate) (1193)+TX, Xiang-HCH (430)+ TX, glyodin (1205)+TX, halfenprox (424)+TX, heptene ether (432)+TX, hexadecane basic ring carboxylate (IUPAC/ chemical abstracts name) (1216)+TX, Hexythiazox (441)+TX, iodomethane (IUPAC titles) (542)+TX, isocarbophos (replacement title) (473)+TX, isopropyl 0- (Methoxyamino thiophosphoryl) salicylate (IUPAC titles) (473)+TX, Ivermectin (replacement title) [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX, iodfenphos (1248)+ TX, lindane (430)+TX, lufenuron (490)+TX, malathion (492)+TX, benzyl malononitrile (malonoben) (1254)+TX, Afos (502)+TX, mephosfolan (1261)+TX, mesulfen (replacement title) [CCN]+TX, methacrifos (1266)+TX, methylamine Phosphorus (527)+TX, methidathion (529)+TX, mercaptodimethur (530)+TX, methomyl (531)+TX, bromomethane (537)+TX, MTMC (550)+TX, Menite (556)+TX, Mexacarbate (1290)+TX, milbemycin (557)+TX, mite killing mattress element oxime (replacement title) [CCN]+TX, mipafox (1293)+TX, Azodrin (561)+TX, morphothion (1300)+TX, Moxidectin (replacement title) [CCN]+TX, 2-dichloroethylk dimethyl phosphate (567)+TX, NC-184 (compound code)+TX, NC-152 (compound code)+TX, the spirit of fluorine mosquito (1309)+TX, nikkomycin (replacement title) [CCN]+TX, nitrilacarb (1313)+TX, nitrilacarb 1:1 zinc chloride complex compound (1313)+TX, NNI-0101 (compound code)+TX, NNI-0250 (compound code)+TX, omethoate (omethoate) (594) + TX, oxamyl (602)+TX, sub- Thiometan (oxydeprofos) (1324)+TX, Disystom-s (1325)+TX, pp '-DDT (219)+TX, parathion (615)+TX, Permethrin (626)+TX, oil (replacement title) (628)+TX, phenkapton (1330)+ TX, phenthoate dimephenthoate cidial (631)+TX, thimet (636)+TX, Phosalone (637)+TX, phosfolan (1338)+TX, phosmet (638)+TX, phosphamidon (639)+TX, phoxim (642)+TX, pirimiphos-methyl (652)+TX, citicide (polychloroterpenes) (traditional title) (1347)+TX, polynactin (polynactins) (replacement title) (653)+ TX, Proclonol (1350)+TX, Profenofos (662)+TX, promacyl (1354)+TX, propargite (671)+TX, propetamphos (673)+ TX, arprocarb (678)+TX, prothidathion (1360)+TX, prothoate (1362)+TX, pyrethrins I (696)+TX, Dalmatian chrysanthemum Ester II (696)+TX, pyrethrin (696)+TX, pyridaben (699)+TX, pyridaphethione (701)+TX, pyrimidifen (706)+TX, Pyrimitate (1370)+TX, quinalphos (711)+TX, quinalphos (1381)+TX, R-1492 (research code) (1382)+TX, RA- 17 (research code) (1383)+TX, rotenone (722)+TX, schradane (1389)+TX, cadusafos (sebufos) (substitute name Claim)+TX, selamectin (replacement title) [CCN]+TX, SI-0009 (compound code)+TX, sophamide (1402)+TX, season ketone Mite ester (738)+TX, Spiromesifen (739)+TX, SSI-121 (research code) (1404)+TX, sulfiram (replacement title) [CCN]+TX, sulfluramid (750)+TX, sulfotep (753)+TX, Sulfur (754)+TX, S21-121 (research code) (757)+ TX, taufluvalinate (398)+TX, tebufenpyrad (763)+TX, TEPP (1417)+TX, terbam (replacement title)+TX, department replace sieve Phosphorus (777)+TX, tetradiphon (786)+TX, polynactin (replacement title) (653)+TX, mite killing thioether (tetrasul) (1425)+TX, thiofanox (thiafenox) (replacement title)+TX, Talcord (1431)+TX, thiofanox (800)+TX, methyl Disulfoton (801)+TX, Eradex (1436)+TX, Su Li rhzomorphs (thuringiensin) (replacement title) [CCN]+TX, prestige mattress Phosphorus (1441)+TX, benzene thiophene mite (1443)+TX, Hostathion (820)+TX, azoles prestige (triazuron) (replacement title)+TX, enemy Hundred worms (824)+TX, the phosphorus of chlorobenzene second third (trifenofos) (1455)+TX, first polynactin (trinactin) (replacement title) (653)+TX, menazon (847)+TX, fluorine pyrazoles worm (vaniliprole) [CCN] and YI-5302 (compound code)+TX,
A kind of algicide, the algicide are selected from the group by following material composition：3- benzos [b] thiophene -2- bases -5,6- two Hydrogen -1,4,2- Evil thiazine -4- oxides [CCN]+TX, two cupric octoates (IUPAC titles) (170)+TX, copper sulphate (172)+TX, Spread net (cybutryne) [CCN]+TX, dihydro naphthoquinones (1052)+TX, antiphen (232)+TX, endothal (295)+TX, three Benzene tin (347)+TX, white lime [CCN]+TX, Dithane A40 (566)+TX, quinoclamine (714)+TX, quinone duckweed amine (quinonamid) (1379)+TX, Simanex (730)+TX, fentin acetate (IUPAC titles) (347) and triphenyltin hydroxide (IUPAC names Claim) (347)+TX,
A kind of anthelmintic, the anthelmintic are selected from the group by following material composition：Abamectin (1)+TX, crufomate (1011)+TX, Doramectin (replacement title) [CCN]+TX, according to mark's fourth (291)+TX, according to mark's butylbenzene formic acid esters (291)+ TX, Eprinomectin (replacement title) [CCN]+TX, ivermectin (replacement title) [CCN]+TX, milbemycin (substitute name Claim) [CCN]+TX, Moxidectin (replacement title) [CCN]+TX, piperazine [CCN]+TX, selamectin (replacement title) [CCN]+ TX, pleocidin (737) and thiophanate (1435)+TX,
A kind of avicide, the avicide are selected from the group by following material composition：Chloralose (127)+TX, endrin (1122)+TX, Entex (346)+TX, pyridine -4- amine (IUPAC titles) (23) and strychnine (745)+TX,
A kind of bactericide, the bactericide are selected from the group by following material composition：1- hydroxyl -1H- pyridine -2- thioketones (IUPAC titles) (1222)+TX, 4- (quinoxaline -2- bases amino) benzsulfamide (IUPAC titles) (748)+TX, 8- hydroxyl quinolines Quinoline sulfate (446)+TX, bronopol (97)+TX, two cupric octoates (IUPAC titles) (170)+TX, Kocide SD (IUPAC names Claim) (169)+TX, cresols [CCN]+TX, antiphen (232)+TX, Dipyrithione (1105)+TX, dodicin (1112)+TX, enemy Sulphur sodium (1144)+TX, formaldehyde (404)+TX, hydrargaphen (replacement title) [CCN]+TX, kasugarnycin (483)+TX, kasugarnycin Hydrochloride hydrate (483)+TX, two (dimethyl dithiocarbamate) nickel (IUPAC titles) (1308)+TX, three chloromethanes Yl pyridines (580)+TX, octhilinone (590)+TX, Oxolinic Acid (606)+TX, terramycin (611)+TX, oxyquinoline potassium sulfate (446)+TX, probenazole (658)+TX, streptomysin (744)+TX, streptomysin sesquisulfate (744)+TX, tecloftalam (766)+TX and thimerosal (replacement title) [CCN]+TX,
A kind of biological reagent, the biological reagent are selected from group constituted by the following substances：Adoxophyes moth PuGV (Adoxophyes orana GV) (replacement title) (12)+TX, agrobacterium radiobacter (replacement title) (13)+TX, Predatory Mites (Amblyseius spp.) (replacement title) (19)+TX, celery looper nucleopolyhedrosis virus (Anagrapha falcifera NPV) (replacement title) (28)+TX, Anagrus atomus (replacement title) (29)+TX, aphid parasitic wasp (Aphelinus Abdominalis) (replacement title) (33)+TX, cotten aphid parasitic wasp (Aphidius colemani) (replacement title) (34)+TX, Eat aphid cecidomyiia (Aphidoletes aphidimyza) (replacement title) (35)+TX, autographa californica nuclear polyhedrosis virus (Autographa californica NPV) (replacement title) (38)+TX, bacillus firmus (Bacillus firmus) (replacement title) (48)+TX, Bacillus sphaericus (Bacillus sphaericus Neide) (scientific name) (49)+TX, Su Yunjin Bacillus (Bacillus thuringiensis Berliner) (scientific name) (51)+TX, bacillus thuringiensis .I (Bacillus thuringiensis subsp.aizawai) (scientific name) (51)+TX, bacillus thuringiensis subsp israelensis (Bacillus thuringiensis subsp.israelensis) (scientific name) (51)+TX, bacillus thuringiensis Japan are sub- Kind (Bacillus thuringiensis subsp.japonensis) (scientific name) (51)+TX, bacillus thuringiensis k. (Bacillus thuringiensis subsp.kurstaki) (scientific name) (51)+TX, bacillus thuringiensis t. (Bacillus thuringiensis subsp.tenebrionis) (scientific name) (51)+TX, ball spore stiff mattress (Beauveria in vain Bassiana) (replacement title) (53)+TX, Bu Shi in vain stiff mattress (Beauveria brongniartii) (replacement title) (54)+ TX, lacewing (Chrysoperla carnea) (replacement title) (151)+TX, Cryptolaemus montrouzieri (Cryptolaemus Montrouzieri) (replacement title) (178)+TX, carpocapsa pomonella granulosis virus (Cydia pomonella GV) (substitute name Claim) (191)+TX, Dacnusa sibirica (Dacnusa sibirica) (replacement title) (212)+TX, a garden pea leaf miner Ji Chalcid fly (Diglyphus isaea) (replacement title) (254)+TX, Encarsia formosa (Encarsia formosa) (scientific name) (293) + TX, eretmocerus SP (Eretmocerus eremicus) (replacement title) (300)+TX, corn earworm nucleopolyhedrosis virus (Helicoverpa zea NPV) (replacement title) (431)+TX, thermophilic mattress heterorhabditis indica (Heterorhabditis Bacteriophora) and H.megidis (replacement title) (433)+TX, considerable ladybug (Hippodamia is assembled Convergens) (replacement title) (442)+TX, tangerine powder scale insect parasitic wasp (Leptomastix dactylopii) (substitute name Claim) (488)+TX, fleahopper (Macrolophus caliginosus) (replacement title) (491)+TX, lopper worm core polyhedral body Virus (Mamestra brassicae NPV) (replacement title) (494)+TX, Metaphycus helvolus (replacement title) (522)+TX, yellowish green green stiff mattress (Metarhizium anisopliae var.acridum) (scientific name) (523)+TX, chafer The small spore mutation of green muscardine fungus (Metarhizium anisopliae var.anisopliae) (scientific name) (523)+TX, neodiprion sertifer (Neodiprion sertifer) nucleopolyhedrosis virus and reddish tone pine bark procyanidins (N.lecontei) nucleopolyhedrosis virus (substitute Title) (575)+TX, minute pirate bugs (replacement title) (596)+TX, paecilomyces fumosoroseus (Paecilomyces Fumosoroseus) (replacement title) (613)+TX, Chile, which catch, plants mite (Phytoseiulus persimilis) (replacement title) (644)+TX, beet armyworm (Spodoptera exigua multicapsid) more nucleocapsid nucleopolyhedrosis virus (scientific name) (741)+TX, march fly nematode (Steinernema bibionis) (replacement title) (742)+TX, nematode Steinernema carpocapsae (Steinernema carpocapsae) (replacement title) (742)+TX, Steinernema feltiae (replacement title) (742)+TX, Steinernema glaseri (replacement title) (742)+TX, Steinernema riobrave (replacement title) (742)+TX, Steinernema riobravis (replacement title) (742)+TX, Steinernema scapterisci (replacement title) (742)+TX, genus steinernema (Steinernema spp.) (replacement title) (742)+TX, Trichogramma spp (replacement title) (826)+TX, west it is blind walk mite (Typhlodromus occidentalis) (replacement title) (844) and lecanium wheel branch mattress (Verticillium lecanii) (replacement title) (848)+TX,
A kind of soil sterilants, the soil sterilants are selected from the group by following material composition：Iodomethane (IUPAC titles) (542) and methyl bromide (537)+TX,
A kind of chemosterilants, the chemosterilants are selected from the group by following material composition：Apholate (apholate) [CCN]+TX, double (aziridine) methylamino phosphine sulfide (bisazir) (replacement title) [CCN]+TX, busulfan (replacement title) [CCN]+TX, diflubenzuron (250)+TX, enlightening wheat are for husband (dimatif) (replacement title) [CCN]+TX, hemel (hemel) [CCN]+TX, hempa (hempa) [CCN]+TX, metepa (metepa) [CCN]+TX, Metapside (methiotepa) [CCN]+TX, sterile spy (methyl apholate) [CCN]+TX, infertile pyridine (morzid) [CCN]+TX, penfluron (penfluron) (replacement title) [CCN]+TX, Aphoxide (tepa) [CCN]+TX, thio hempa (thiohempa) (substitute name Claim) [CCN]+TX, thio-tepa (replacement title) [CCN]+TX, tretamine (replacement title) [CCN] and uredepa (replacement name Claim) [CCN]+TX,
A kind of insect pheromone, the insect pheromone are selected from the group by following material composition：(E)-decyl- 5- alkene -1- base second Acid esters and (E)-decyl- 5- alkene -1- alcohol (IUPAC titles) (222)+TX, (E)-ten three carbon -4- alkene -1- yl acetate (IUPAC names Claim) (829)+TX, (E) -6- methyl hept-2-ene" -4- alcohol (IUPAC titles) (541)+TX, (E, Z)-ten four carbon -4,10- diene - 1- yl acetates (IUPAC titles) (779)+TX, (Z)-ten two carbon -7- alkene -1- yl acetates (IUPAC titles) (285)+TX, (Z)-ten six carbon -11- olefine aldehydrs (IUPAC titles) (436)+TX, (Z)-ten six carbon -11- alkene -1- yl acetates (IUPAC titles) (437)+TX, (Z)-ten six carbon -13- alkene -11- alkynes -1- yl acetates (IUPAC titles) (438)+TX, (Z)-two ten -13- alkene - 10- ketone (IUPAC titles) (448)+TX, (Z)-ten four carbon -7- alkene -1- aldehyde (IUPAC titles) (782)+TX, (Z)-ten four carbon - 9- alkene -1- alcohol (IUPAC titles) (783)+TX, (Z)-ten four carbon -9- alkene -1- yl acetates (IUPAC titles) (784)+TX, (7E, 9Z)-ten two carbon -7,9- diene -1- yl acetates (IUPAC titles) (283)+TX, (9Z, 11E)-ten four carbon -9,11- two Alkene -1- yl acetates (IUPAC titles) (780)+TX, (9Z, 12E)-ten four carbon -9,12- diene -1- yl acetate (IUPAC names Claim) (781)+TX ,-1- alkene of 14- methyl 18 (IUPAC titles) (545)+TX, 4- methyl aldehyde C-9-5- alcohol and 4- methyl aldehyde C-9- 5- ketone (IUPAC titles) (544)+TX, α-more texels (multistriatin) (replacement title) [CCN]+TX, western loose bark beetle Assembly pheromone (brevicomin) (replacement title) [CCN]+TX, Pherocon CM (codlelure) (replacement title) [CCN]+TX, Pherocon CM (codlemone) (replacement title) (167)+TX, cue-lure (cuelure) (replacement title) (179)+TX, Disparmone (277)+TX, the yl acetate of 12 carbon -8- alkene -1 (IUPAC titles) (286)+TX, 12 carbon - 9- alkene -1- yl acetates (IUPAC titles) (287)+TX, 12 carbon -8+TX, 10- diene -1- yl acetates (IUPAC titles) (284)+TX, dominicalure (replacement title) [CCN]+TX, 4- methyloctanoic acids ethyl ester (IUPAC titles) (317)+TX, fourth Fragrant phenol (replacement title) [CCN]+TX, dendroctonus frontalis assembly pheromone (frontalin) (replacement title) [CCN]+TX, lure worm Hexadecyl ester (gossyplure) (replacement title) (420)+TX, Grandemone (grandlure) (421)+TX, Grandemone I (replacement title) (421)+TX, Grandemone II (replacement title) (421)+TX, Grandemone III (replacement title) (421)+TX, Grandemone IV (replacement title) (421)+TX, hexalure (hexalure) [CCN]+TX, tooth bark beetle Dienol (ipsdienol) (replacement title) [CCN]+TX, small stupid enol (ipsenol) (replacement title) [CCN]+TX, cockchafer Sub- gyplure (japonilure) (replacement title) (481)+TX, lineatin (replacement title) [CCN]+TX, litlure (are replaced Code name claims) [CCN]+TX, looplure (looplure) (replacement title) [CCN]+TX, Medlure (medlure) [CCN]+TX, megatomoic acid (replacement title) [CCN]+TX, Allylveratrole (methyl eugenol) (replacement title) (540)+TX, muscalure (muscalure) (563)+TX, 18-2,13- diene-1- yl acetates (IUPAC titles) (588)+ TX, 18-3,13- diene-1- yl acetates (IUPAC titles) (589)+TX, He Kangbi (orfralure) (replacement title) [CCN]+TX, oryctalure (replacement title) (317)+TX, Fei Lekang (ostramone) (replacement title) [CCN]+TX, lure Worm ring (siglure) [CCN]+TX, sordidin (replacement title) (736)+TX, sulcatol (replacement title) [CCN]+ TX, 14-11- alkene-1- yl acetates (IUPAC titles) (785)+TX, spy lure ketone (839)+TX, spy to lure ketone A (other rock) (839) + TX, spy lure ketone B1(replacement title) (839)+TX, spy lure ketone B2(replacement title) (839)+TX, spy lure ketone C (replacement title) (839) and trunc-call (replacement title) [CCN]+TX,
A kind of insect repellent, the insect repellent are selected from the group of following material composition：2- (octylsulfo) ethanol (IUPAC titles) (591)+TX, dihydropyrone (butopyronoxyl) (933)+TX, butoxy (polypropylene glycol) (936)+TX, oneself Adipate (IUPAC titles) (1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC names Claim) (1048)+TX, Metadelphene [CCN]+TX, Metadelphene [CCN]+TX, dimethyl phthalate (dimethyl carbate) [CCN]+TX, Ethohexadiol (1137)+TX, own urea [CCN]+TX, first quinoline fourth (methoquin-butyl) (1276)+TX, the new caprinoyl of methyl Amine [CCN]+TX, oxamic acid ester (oxamate) [CCN] and Icaridin [CCN]+TX,
A kind of insecticide, the insecticide are selected from the group by following material composition：momfluorothrin[609346- 29-4]+TX, pyrazine ethiprole (pyrafluprole) [315208-17-4]+TX, flometoquin [875775-74-9]+ TX, fluorine pyrrole furanone (flupyradifuron) [951659-40-8]+TX, the chloro- 1- nitroethanes of 1- bis- (IUPAC/ chemistry texts Pluck title) (1058)+TX, bis- chloro- 2,2- of 1,1- double (4- ethylphenyls) ethane (IUPAC titles) (1056)+TX, 1,2- dichloros Propane (IUPAC/ Chemical Abstracts names) (1062)+TX, 1,2- dichloropropanes and 1,3- dichloropropylenes (IUPAC titles) (1063) The bromo- 2- chloroethanes of+TX, 1- (IUPAC/ Chemical Abstracts names) (916)+TX, tri- chloro- 1- of acetic acid 2,2,2- (3,4- dichlorophenyls) Ethyl ester (IUPAC titles) (1451)+TX, phosphoric acid 2,2- dichloroethylene 2- ethylsulfinyl ethyl-methyl ester (IUPAC names Claim) (1066)+TX, dimethyl carbamic acid 2- (1,3- dithiolane -2- bases) phenylester (IUPAC/ Chemical Abstracts names) (1109)+TX, thiocyanic acid 2- (2- Butoxyethoxies) ethyl ester (IUPAC/ Chemical Abstracts names) (935)+TX, methylamino Formic acid 2- (4,5- dimethyl -1,3- dioxolanes -2- bases) phenylester (IUPAC/ Chemical Abstracts names) (1084)+TX, 2- (4- Chloro- 3,5- xylyloxies) ethanol (IUPAC titles) (986)+TX, phosphoric acid 2- chlorovinyls diethyl ester (IUPAC titles) (984)+TX, 2- imidazolones (IUPAC titles) (1225)+TX, 2- isovaleryl indane -1,3- diketone (IUPAC titles) (1246)+TX, methyl carbamic acid 2- methyl (Propargyl) aminobenzene base ester (IUPAC titles) (1284)+TX, laurate 2- Thiocyanatos ethyl ester (IUPAC titles) (1433)+TX, the bromo- 1- chlorine propyl- 1- alkene of 3- (IUPAC titles) (917)+TX, two Methyl carbamic acid 3- methyl isophthalic acids-Phenylpyrazole -5- base esters (IUPAC titles) (1283)+TX, methyl carbamic acid 4- methyl (Propargyl) amino -3,5- dimethylbenzene base ester (IUPAC titles) (1285)+TX, dimethyl carbamic acid 5,5- dimethyl - 3- oxocyclohexyl -1- alkenyl esters (IUPAC titles) (1085)+TX, abamectin (1)+TX, accephate (2)+TX, Acetamiprid (4)+TX, Acethion (replacement title) [CCN]+TX, acetyl worm nitrile [CCN]+TX, acrinathrin (9)+TX, acrylonitrile (IUPAC Title) (861)+TX, alanycarb (15)+TX, Aldicarb (16)+TX, aldoxycarb (863)+TX, drinox (864)+TX, third Alkene chrysanthemum ester (17)+TX, A Luo ammonia rhzomorph (replacement title) [CCN]+TX, allyxycarb (866)+TX, α-cypermethrin (202)+TX, α-moulting hormone (replacement title) [CCN]+TX, aluminum phosphate (640)+TX, match result (870)+TX, by phosphamide (872)+TX, aminocarb (873)+TX, Citram (875)+TX, oxalic acid hydrogen Citram (875)+TX, Amitraz (24)+TX, poison Chenopodine (877)+TX, ethyl methidathion (883)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+ TX, nimbin (replacement title) (41)+TX, methylpyridine phosphorus (42)+TX, azinphos-methyl-ethyl (44)+TX, azinphos-methyl-methyl (45)+TX, Alamos (889)+TX, bacillus thuringiensis δ endotoxin (replacement title) (52)+TX, hexafluorosilicic acid barium (substitute Title) [CCN]+TX, solbar (IUPAC/ Chemical Abstracts names) (892)+TX, smoked chrysanthemum ester [CCN]+TX, bayer 22/190 (research code) (893)+TX, Bayer 22408 (research code) (894)+TX, Ficam (58)+TX, Benfuracard micro (60)+ TX, bensultap (66)+TX, β-cyfloxylate (194)+TX, β-cypermethrin (203)+TX, Biphenthrin (76)+TX, biology Allethrin (78)+TX, EXTHIN S- cyclopentenyls isomers (replacement title) (79)+TX, penta ring resmethrin [CCN]+TX, biopermethrin (908)+TX, chrysron (80)+TX, double (2- chloroethyls) ethers (IUPAC titles) (909)+ TX, bistrifluron (83)+TX, borax (86)+TX, brofenxalerate (replacement title)+TX, bromobenzene alkene phosphorus (914)+TX, bromine alkene Kill (918)+TX, bromo- DDT (replacement title) [CCN]+TX, bromophos (920)+TX, bromophos-ethyl (921)+TX, metalkamate (924)+TX, Buprofezin (99)+TX, butacarb (926)+TX, special Pyrimitate (927)+TX, butocarboxim (103)+TX, butonate (932)+TX, butanone sulfone prestige (104)+TX, butyl pyridaben (replacement title)+TX, cadusafos (109)+TX, calcium arsenate [CCN]+ TX, cyanogas (444)+TX, calcium polysulfide (IUPAC titles) (111)+TX, toxaphene (941)+TX, sok (943)+ TX, sevin (115)+TX, carbofuran (118)+TX, carbon disulfide (IUPAC/ Chemical Abstracts names) (945)+TX, tetrachloro Change carbon (IUPAC titles) (946)+TX, carbophenothion (947)+TX, carbosulfan (119)+TX, cartap (123)+TX, hydrochloric acid Cartap (123)+TX, cevadine (replacement title) (725)+TX, chlorbicyclen (960)+TX, Niran (128)+TX, chlordecone (963)+TX, Spanon (964)+TX, hydrochloric acid Spanon (964)+TX, chlorethoxyfos (129)+TX, chlorfenapyr (130)+TX, poisonous insect Fear (131)+TX, chlorfluazuron (132)+TX, chlormephos (136)+TX, chloroform [CCN]+TX, chloropicrin (141)+TX, chlorphoxim (989)+TX, chlorine pyrazoxon (990)+TX, chlopyrifos (145)+TX, chlopyrifos-methyl (146)+TX, Actellic (994)+TX, Ring tebufenozide (150)+TX, cinerin (696)+TX, cinerin I (696)+TX, cinerin (696)+TX, cis- chrysron (replacement title)+TX, cis resmethrin (80)+TX, Cyhalothrin (replacement title)+TX, worm prestige (999)+TX, chlorine Cyanogen iodine willow amine (replacement title) [CCN]+TX, clothianidin (165)+TX, copper acetoarsenite [CCN]+TX, copper arsenate [CCN]+ TX, copper oleate [CCN]+TX, Resistox (174)+TX, Dithion (1006)+TX, Crotamiton (replacement title) [CCN]+TX, Crotoxyphos (1010)+TX, Ruelene (1011)+TX, ice crystal (replacement title) (177)+TX, CS 708 (research code) (1012)+TX, Surecide (1019)+TX, cynock (184)+TX, cyanthoate (1020)+TX, cyclethrin [CCN]+TX, second Cyanogen chrysanthemum fat (188)+TX, cyfloxylate (193)+TX, Cyhalothrin (196)+TX, cypermethrin (201)+TX, benzene cyanogen Chrysanthemum ester (206)+TX, cyromazine (209)+TX, cythioate (replacement title) [CCN]+TX, (R)-4-isopropenyl-1-methyl-1-cyclohexene (replacement title) [CCN]+ TX, d- tetramethrin (replacement title) (788)+TX, DAEP (1031)+TX, dazomet (216)+TX, DDT (219)+TX, a first furans Pellet (1034)+TX, decis (223)+TX, demephion (1037)+TX, demephion-O (1037)+TX, demephion-S (1037) + TX, demeton (1038)+TX, demeton-methyl (224)+TX, demeton-O (1038)+TX, demeton-O- methyl (224)+ TX, demeton-S (1038)+TX, demeton-S- methyl (224)+TX, horizontal suction are sympathized with (demeton-S-methylsulphon) (1039)+TX, diafenthiuron (226)+TX, dialifos (1042)+TX, diamines phosphorus (1044)+TX, basudin (227)+TX, Isochlorothion (1050)+TX, dichlofenthion (1051)+TX, DDVP (236)+TX, two grams of phosphorus (replacement title)+TX, enemy come extremely (replacement title) [CCN]+TX, Carbicron (243)+TX, Dicyclanil (244)+TX, dieldrite (1070)+TX, 5- methyl pyrroles Azoles -3- base p diethylaminobenzoic acids base ester (IUPAC titles) (1076)+TX, diflubenzuron (250)+TX, neutraphylline (replacement title) [CCN]+TX, dimefluthrin [CCN]+TX, BFPO (1081)+TX, dimetan (1085)+TX, Rogor (262)+TX, benzyl Bacterium ester (1083)+TX, dimethylvinphos (265)+TX, dimetilan (1086)+TX, Dinitrocyclohexylphenol (1089)+TX, Dinitrocyclohexylphenol (dinex-diclexine) (1089)+TX, third nitre phenol (1093)+TX, dinosam (1094)+TX, dinoseb (1095)+TX, furan Worm amine (271)+TX, difenolan (1099)+TX, salithion (1100)+TX, Elacron (1101)+TX, dioxathion (1102)+TX, Disulfoton (278)+TX, thiapyran phosphorus (1108)+TX, DNOC (282)+TX, doractin (replacement title) [CCN]+TX, DSP (1115)+TX, ecdysterone (replacement title) [CCN]+TX, EI 1642 (research code) (1118)+TX, methylamino Avermectin Element (291)+TX, emamectin-benzoate (291)+TX, EMPC (1120)+TX, Prallethrin (292)+TX, 5a,6,9,9a-hexahydro-6,9-methano-2,4 (294)+TX, endothion (1121)+TX, Antorane (1122)+TX, EPBP (1123)+TX, EPN (297)+TX, the young ether of guarantor (1124)+TX, Eprinomectin (replacement title) [CCN]+TX, esfenvalerate (302)+TX, Yi Tafu are killed (replacement title) [CCN]+TX, benthiocarb (308)+TX, Ethodan (309)+TX, ethiprole (310)+TX, beneficial fruit-methyl (1134)+TX, go out line Phosphorus (312)+TX, Ethyl formate (IUPAC titles) [CCN]+TX, ethyl-DDD (replacement title) (1056)+TX, ethylene dibromide (316)+TX, ethylene dichloride (chemical name) (1136)+TX, oxirane [CCN]+TX, ethofenprox (319)+TX, the phonetic sulphur of second Phosphorus (1142)+TX, EXD (1143)+TX, Dovip (323)+TX, Nemacur (326)+TX, fenazaflor (1147)+TX, torsalo sulphur Phosphorus (1148)+TX, ethylbenzene prestige (1149)+TX, fenfluthrin (1150)+TX, fenifrothion (335)+TX, Bassa (336)+ TX, non-Nochlin (1153)+TX, fenoxycarb (340)+TX, fenpirithrin (1155)+TX, Fenpropathrin (342)+TX, pyrrole mite Amine (replacement title)+TX, fensulfothion (1158)+TX, Entex (346)+TX, Entex-ethyl [CCN]+TX, fenvalerate (349)+TX, ethiprole (354)+TX, fluorine Buddhist nun amine (358)+TX, fipronil bisamide (CAS Registry Number：272451-65-7)+TX、 Lie prostrate health urea (1168)+TX, flucycloxuron (366)+TX, flucythrinate (367)+TX, Fluenyl (1169)+TX, phonetic worm amine [CCN] + TX, Flufenoxuron (370)+TX, trifluoro (1171)+TX, flumethrin (372)+TX, taufluvalinate (1184)+TX, FMC 1137 (research code) (1185)+TX, Dyfonate (1191)+TX, medimeform (405)+TX, hydrochloric acid medimeform (405)+TX, peace Fruit (1192)+TX, amine first prestige (1193)+TX, fosmethilan (1194)+TX, fospirate (1195)+TX, lythidathion (408)+ TX, fosthietan (1196)+TX, furathiocarb (412)+TX, furethrin (1200)+TX, γ-Cyhalothrin (197)+TX, γ-HCH (430)+TX, Guanoctine (422)+TX, acetic acid Guanoctine (422)+TX, GY-81 (research code) (423)+TX, benzyl mite Ether (424)+TX, chlorine tebufenozide (425)+TX, HCH (430)+TX, HEOD (1070)+TX, heptachlor (1211)+TX, heptenophos (432)+TX, speed kill sulphur phosphorus [CCN]+TX, HEXAFLUMURON (439)+TX, HHDN (864)+TX, hydramethylnon (443)+TX, hydrogen cyanide (444)+TX, hydroprene (445)+TX, put forth energy leaching prestige (1223)+TX, imidacloprid (458)+TX, Imiprothrin (460)+TX, indenes Worm prestige (465)+TX, iodomethane (IUPAC titles) (542)+TX, IPSP (1229)+TX, fenamiphos (1231)+TX, Telodrin (1232)+TX, isocarbophos (replacement title) (473)+TX, isodrin (1235)+TX, isofenphos (1236)+TX, transplanting spirit (1237)+TX, isoprocarb (472)+TX, O- (Methoxyamino thiophosphoryl) salicylic acid isopropyl esters (IUPAC titles) (473)+TX, Isoprothiolane (474)+TX, isothioate (1244)+TX, isoxathion (480)+TX, ivermectin (replacement title) [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX, iodfenphos (1248)+TX, juvenile hormone I (are substituted Title) [CCN]+TX, juvenile hormone II (replacement title) [CCN]+TX, juvenile hormone III (replacement title) [CCN]+TX, chlorine penta Ring (1249)+TX, kinoprene (484)+TX, λ-Cyhalothrin (198)+TX, lead arsenate [CCN]+TX, thunder cuticulin (CCN)+TX, leptophos (1250)+TX, lindane (430)+TX, pyridine worm phosphorus (1251)+TX, Lufenuron (490)+TX, lythidathion (1253) isopropylbenzene base ester (IUPAC titles) (1014)+TX, magnesium phosphide (IUPAC titles) (640) between+TX, methyl carbamic acid + TX, malathion (492)+TX, third mite cyanogen (1254)+TX, mazidox (1255)+TX, Afos (502)+TX, methyl subtract aphid Phosphorus (1258)+TX, menazon (1260)+TX, mephosfolan (1261)+TX, calogreen (513)+TX, first oxydemeton_methyl (1263)+ TX, metaflumizone (CCN)+TX, metham-sodium (519)+TX, metham-sodium-potassium (replacement title) (519)+TX, metham-sodium-sodium (519) + TX, methacrifos (1266)+TX, acephatemet (527)+TX, fluorination mesyl (IUPAC/ Chemical Abstracts names) (1268)+TX, Methidathion (529)+TX, mercaptodimethur (530)+TX, desinsection ethephon (1273)+TX, methomyl (531)+TX, methoprene (532)+ TX, quinacrine-butyl (1276)+TX, methothrin (replacement title) (533)+TX, methoxychlor (534)+TX, methoxy Tebufenozide (535)+TX, methyl bromide (537)+TX, methyl-isorhodanate (543)+TX, methyl chloroform (replacement title) [CCN]+ TX, chloromethane [CCN]+TX, metofluthrin [CCN]+TX, MTMC (550)+TX, metoxadiazone (1288)+TX, speed are gone out Phosphorus (556)+TX, mexacarbate (1290)+TX, close spit of fland of going out (557)+TX, milbemycin oxime (replacement title) [CCN]+TX, mipafox (1293)+TX, mirex (1294)+TX, Azodrin (561)+TX, morphothion (1300)+TX, Moxidectin (replacement title) [CCN]+TX, Naftalofos (replacement title) [CCN]+TX, 2-dichloroethylk dimethyl phosphate (567)+TX, naphthalene (IUPAC/ Chemical Abstracts names) (1303) + TX, NC-170 (research code) (1306)+TX, NC-184 (compound code)+TX, nicotine (578)+TX, nicotine sulphate (578)+TX, nifluridide (1309)+TX, Nitenpyram (579)+TX, nithiazide (1311)+TX, nitrilacarb (1313)+ TX, nitrilacarb 1:1 zinc chloride complex compound (1313)+TX, NNI-0101 (compound code)+TX, NNI-0250 (compound generations Code)+TX, nornicotine (traditional title) (1319)+TX, Rimon (585)+TX, noviflumuron (586)+TX, ethylenebis dithiocarbamate phosphonic acids The chloro- 4- iodophenyls O- ethyl esters of O-5- bis- (IUPAC titles) (1057)+TX, D2EHDTPA O, O- diethyl O-4- methyl -2- oxygen Generation -2H- chromene -7- base esters (IUPAC titles) (1074)+TX, D2EHDTPA O, O- diethyl O-6- methyl-2-propyls pyrimidine - 4- base esters (IUPAC titles) (1075)+TX, two thio pyrophosphoric acid O, O, O ', O '-tetrapropyl ester (IUPAC titles) (1424)+ TX, oleic acid (IUPAC titles) (593)+TX, omethoate (594)+TX, oxamoyl (602)+TX, oxydemeton_methyl (oxydemeton- Methyl) (609)+TX, oxydeprofos (1324)+TX, Disystom-s (1325)+TX, the thiopyrophosphate of pp ' O '-tetrapropyl two (IUPAC titles) (1424)+TX, octadecenic acid (IUPAC titles) (593)+TX, omethoate (omethoate) (594)+TX, grass Aminoacyl (602)+TX, metilomerkaptofosoksid (oxydemeton-methyl) (609)+TX, oxydeprofos (1324)+TX, Disystom-s (1325) + TX, pp '-DDT (219)+TX, paracide [CCN]+TX, parathion (615)+TX, parathion-methyl (616)+TX, fluorine children Urea (replacement title) [CCN]+TX, pentachlorophenol (623)+TX, laurate pentachlorobenzene base ester (IUPAC titles) (623)+TX, benzyl Permethrin (626)+TX, oil (replacement title) (628)+TX, PH 60-38 (research code) (1328)+TX, phenkapton (1330)+TX, phenothrin (630)+TX, phenthoate dimephenthoate cidial (631)+TX, thimet (636)+TX, zolone (637)+TX, sulphur ring Phosphorus (1338)+TX, phosmet (638)+TX, nichlorfos (1339)+TX, phosphamidon (639)+TX, phosphine (IUPAC titles) (640)+TX, phoxim (642)+TX, phoxim-methyl (1340)+TX, methylamine crow phosphorus (1344)+TX, Aphox (651)+ TX, Diothyl-ethyl (1345)+TX, Diothyl-methyl (652)+TX, polychlorostyrene bicyclopentadiene isomers (IUPAC titles) (1346)+TX, polychlorostyrene terpenes (traditional title) (1347)+TX, potassium arsenite [CCN]+TX, potassium rhodanide [CCN]+TX, alkynes third Chrysanthemum ester (655)+TX, precocene I (replacement title) [CCN]+TX, precocene II (replacement title) [CCN]+TX, precocene III (replacement title) [CCN]+TX, acetyl pyrimidine phosphorus (1349)+TX, Profenofos (662)+TX, the third Flumethrin [CCN]+TX, promacyl (1354)+TX, Carbamult (1355)+TX, Kayaphos (1356)+TX, Propetamphos (673)+TX, arprocarb (678)+TX, second thiophene Azoles phosphorus (1360)+TX, Toyodan (686)+TX, prothoate (1362)+TX, propyl benzene hydrocarbon chrysanthemum ester [CCN]+TX, pymetrozine (688)+ TX, pyraclofos (689)+TX, Ppyrazophos (693)+TX, anti-Chryson (1367)+TX, pyrethrins I (696)+TX, Dalmatian chrysanthemum Ester II (696)+TX, pyrethrins (696)+TX, pyridaben (699)+TX, pyridalyl (700)+TX, pyridaphethione (701)+ TX, pyrimidifen (706)+TX, Pyrimitate (1370)+TX, Nylar (708)+TX, quassia (replacement title) [CCN]+TX, quinoline are disliked Phosphorus (711)+TX, diethquinalphione-methyl (1376)+TX, peaceful phosphorus (the 1380)+TX of poultry, quinalphos (1381)+TX, R-1492 (research generations Code) (1382)+TX, iodo-ether salicylamine (replacement title) [CCN]+TX, chrysron (719)+TX, rotenone (722)+TX, RU 15525 (research code) (723)+TX, RU 25475 (research code) (1386)+TX, ryania (replacement title) (1387)+ TX, ryanodine (traditional title) (1387)+TX, sabadilla (replacement title) (725)+TX, schradane (1389)+TX, gram Line pellet (replacement title)+TX, selamectin (replacement title) [CCN]+TX, SI-0009 (compound code)+TX, SI-0205 (compound code)+TX, SI-0404 (compound code)+TX, SI-0405 (compound code)+TX, silafluofene (728)+ TX, SN 72129 (research code) (1397)+TX, sodium arsenite [CCN]+TX, Cymag (444)+TX, sodium fluoride (IUPAC/ Chemical Abstracts name) (1399)+TX, sodium hexafluorisilicate (1400)+TX, penta sodium pentachlorophenate (623)+TX, sodium selenate (IUPAC titles) (1401)+TX, sodium sulfocyanate [CCN]+TX, sophamide (1402)+TX, pleocidin (737)+TX, Spiromesifen (739)+TX, Grand (the 746)+TX of spiral shell worm ethyl ester [CCN]+TX, sulphur phenylate, sulphur phenylate be grand-sodium (746)+TX, sulfluramid (750)+TX, sulfotep (753)+TX, fluorination sulfonyl (756)+TX, sulprofos (1408)+TX, tar (replacement title) (758)+TX, taufluvalinate (tau-fluvalinate) (398)+TX, tazimcarb (1412)+TX, TDE (1414)+TX, tebufenozide (762)+TX, tebufenpyrad (763)+TX, butyl pyrimidine phosphorus (764)+TX, fluorobenzene urea (768)+TX, Tefluthrin (769)+TX, Swebate (770)+TX, TEPP (1417)+TX, terallethrin (1418)+TX, terbam (replacement title)+TX, Terbufos (773)+TX, four chloroethenes Alkane [CCN]+TX, Ravap (777)+TX, tetramethrin (787)+TX, θ-cypermethrin (204)+TX, thiacloprid (791)+TX, thiophene Fen Nuo (replacement title)+TX, Diacloden (792)+TX, benzene thiophene sulphur phosphorus (1428)+TX, Talcord (1431)+TX, thiocyclam (798)+TX, oxalic acid hydrogen thiocyclam (798)+TX, sulphur enemy gram (799)+TX, thiofanox (800)+TX, thiometon (801)+ TX, nemaphos (1434)+TX, dimehypo (803)+TX, dimehypo (thiosultap-sodium) (803)+TX, thuringiensin (replacement title) [CCN]+TX, Tolfenpyrad (809)+TX, tralomethrin (812)+TX, transfluthrin (813)+TX, anti-chlorine Chrysanthemum ester (1440)+TX, triamiphos (1441)+TX, triaguron (818)+TX, Hostathion (820)+TX, azoles prestige (replacement title)+ TX, trichlorfon 98 (824)+TX, different Nankor -3 (replacement title) [CCN]+TX, trichloronat (1452)+TX, trichlorine the third oxygen phosphorus (1455) grand (the 835)+TX of+TX, desinsection, Landrin (840)+TX, triprene (1459)+TX, Kilval (847)+TX, fluorine pyrrole Azoles worm [CCN]+TX, veratridine (replacement title) (725)+TX, jervine (replacement title) (725)+TX, XMC (853)+TX, go out Kill prestige (854)+TX, YI-5302 (compound code)+TX, ξ-cypermethrin (205)+TX, own body cypermethrin (replacement title) + TX, zinc phosphide (640)+TX, the general phosphorus of Zola (1469) and ZXI 8901 (research code) (858)+TX, bromine cyanogen insect amide [736994-63-19]+TX, Rynaxypyr [500008-45-7]+TX, azoles mite cyanogen [560121-52-0]+TX, fourth fluorine mite Ester [400882-07-7]+TX, fluorine worm pyrrole quinoline [337458-27-2]+TX, ethyl pleocidin [187166-40-1+187166- 15-0]+TX, spiral shell worm ethyl ester [203313-25-1]+TX, sulfoxaflor [946578-00-3]+TX, butene-fipronil [704886-18-0]+TX, fluorine chlorine ether chrysanthemum ester [915288-13-0]+TX, etrafluorine ethofenprox [84937-88-2]+TX and one kind Compound with chemical formula B1
(there is common first names triflumezopyrim (being disclosed in WO 2012/092115))+TX；
A kind of invertebrate poison, the invertebrate poison are selected from the group by following material composition：Two (tributyl tin) oxygen Compound (IUPAC titles) (913)+TX, acetbromamide [CCN]+TX, calcium arsenate [CCN]+TX, cloethocarb (cloethocarb) (999)+TX, copper acetoarsenite [CCN]+TX, copper sulphate (172)+TX, fentin (347)+TX, ferric phosphate (IUPAC titles) (352)+TX, the methaldehyde (518)+TX, mercaptodimethur (530)+TX, niclosamidum (576)+TX, bayluscid (576)+TX, pentachlorophenol (623)+TX, pentachlorobenzene sodium oxide molybdena (623)+TX, tazimcarb (tazimcarb) (1412)+TX, sulphur are double Prestige (799)+TX, tributyltin oxide (913)+TX, trifenmorph (trifenmorph) (1454)+TX, Landrin (trimethacarb) (840)+TX, triphenyltin acetate (IUPAC titles) (347) and triphenyl tin hydroxide (IUPAC names Claim) (347)+TX, Pi Ruipu (pyriprole) [394730-71-3]+TX,
A kind of nematicide, the nematicide are selected from the group by following material composition：AKD-3088 (compound code)+ The bromo- 3- chloropropanes of TX, 1,2- bis- (IUPAC/ chemical abstracts name) (1045)+TX, 1,2- dichloropropanes (IUPAC/ chemical abstracts Name) (1062)+TX, 1,2- dichloropropanes and 1,3- dichloropropylenes (IUPAC titles) (1063)+TX, 1,3- dichloropropylenes (233) + TX, 3,4- dichloro thiophane 1,1- dioxide (IUPAC/ chemical abstracts name) (1065)+TX, 3- (4- chlorphenyls) -5- first Base rhodanine (IUPAC titles) (980)+TX, the thio -1,3,5- thiadiazines alkane -3- guanidine-acetic acids of 5- methyl -6- (IUPAC titles) (1286)+TX, 6- isopentene groups adenine phosphate (replacement title) (210)+TX, abamectin (1)+TX, acetyl worm nitrile [CCN]+ TX, alanycarb (15)+TX, Aldicarb (aldicarb) (16)+TX, aldoxycarb (aldoxycarb) (863)+TX, AZ60541 (compound code)+TX, benclothiaz [CCN]+TX, benzene mattress spirit (62)+TX, butyl pyridaben (butylpyridaben) (replacement title)+TX, cadusafos (cadusafos) (109)+TX, carbofuran (carbofuran) (118)+TX, carbon disulfide (945)+TX, carbosulfan (119)+TX, chloropicrin (141)+TX, chlopyrifos (145)+TX, cloethocarb (cloethocarb) (999)+TX, the basic element of cell division (cytokinins) (replacement title) (210)+TX, dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, Nellite (diamidafos) (1044)+TX, dichlofenthion (dichlofenthion) (1051)+TX, two grams Phosphorus (dicliphos) (replacement title)+TX, Rogor (262)+TX, according to mark's fourth (replacement title) [CCN]+TX, benzoic acid according to horse Gram fourth (291)+TX, Eprinomectin (291)+TX, (replacement title) [CCN]+TX, phonamiphos (312)+TX, Bromofume (316)+TX, fenamiphos (fenamiphos) (326)+TX, tebufenpyrad (replacement title)+TX, fensulfothion (fenpyrad) (1158)+TX, lythidathion (fosthiazate) (408)+TX, fosthietan (fosthietan) (1196)+TX, furfural (substitute Title) [CCN]+TX, GY-81 (research code) (423)+TX, speed kills sulphur phosphorus (heterophos) [CCN]+TX, iodomethane (IUPAC titles) (542)+TX, isamidofos (1230)+TX, isazofos (isazofos) (1231)+TX, kinetin (kinetin) (replacement title) [CCN]+TX, chaff adenine phosphate (mecarphon) (replacement title) (210)+TX, methyl go out aphid Phosphorus (mecarphon) (1258)+TX, metham-sodium (519)+TX, metham-sodium sylvite (replacement title) (519)+TX, metham-sodium sodium salt (519)+TX, methyl bromide (537)+TX, methyl-isorhodanate (543)+TX, polynactin oxime (milbemycin oxime) (replace Code name claims) [CCN]+TX, Moxidectin (picking name) [CCN]+TX, wart spore paint spot mattress (Myrothecium verrucaria) component (replacement title) (565)+TX, NC-184 (compound code)+TX, oxamyl (602)+TX, thimet (636)+TX, phosphamidon (639)+TX, phosphorus worm prestige (phosphocarb) [CCN]+TX, cadusafos (sebufos) (replacement title)+TX, selamectin (selamectin) (replacement title) [CCN]+TX, pleocidin (737)+TX, terbam (terbam) (replacement title)+TX, Terbufos (terbufos) (773)+TX, penphene (IUPAC/ chemical abstracts name) (1422)+TX, thiaf enox (are substituted Title)+TX, thionazin (thionazin) (1434)+TX, Hostathion (triazophos) (820)+TX, triazuron (substitute Title)+TX, xylenols [CCN]+TX, YI-5302 (compound code) and zeatin (replacement title) (210)+TX, Fluensulfone [318290-98-1]+TX,
A kind of nitrification inhibitor, the nitrification inhibitor are selected from the group by following material composition：Ethoxy-dithioformic acid Potassium [CCN] and chlorine pyridine (nitrapyrin) (580)+TX,
A kind of activating plants agent, the activating plants agent are selected from the group by following material composition：Thiadiazoles element (acibenzolar) (6)+TX, thiadiazoles element-S- methyl (6)+TX, probenazole (probenazole) (658) and big tiger Cane (Reynoutria sachalinensis) extract (replacement title) (720)+TX,
A kind of rat poison, the rat poison are selected from the group by following material composition：2- isovaleryl indane -1,3- diketone (IUPAC Title) (1246)+TX, 4- (quinoxaline -2- bases amino) benzsulfamide (IUPAC titles) (748)+TX, alpha-chloro alcohol [CCN]+ TX, aluminum phosphate (640)+TX, ANTU (880)+TX, arsenic trioxide (882)+TX, barium carbonate (891)+TX, double mouse ureas (912)+ TX, Talon (89)+TX, Bromadiolone (91)+TX, bromethalin (92)+TX, cyanogas (444)+TX, Chloralose (127)+TX, chlorine Mouse ketone (140)+TX, vitamine D3 (replacement title) (850)+TX, coumachlor (1004)+TX, coumafuryl (1005)+TX, kill Mouse naphthalene (175)+TX, crimidine (1009)+TX, difenacoum (246)+TX, difethialone (249)+TX, diphacine-Na (273)+TX, Calciferol (301)+TX, flocoumafen (357)+TX, Fluorakil 100 (379)+TX, mouse Piao Ding (1183)+TX, hydrochloric acid mouse Piao Ding (1183)+TX, γ-HCH (430)+TX, HCH (430)+TX, hydrogen cyanide (444)+TX, iodomethane (IUPAC titles) (542)+ TX, woods denier (430)+TX, magnesium phosphide (IUPAC titles) (640)+TX, methyl bromide (537)+TX, Shoxin (1318)+TX, malicious mouse Phosphorus (1336)+TX, hydrogen phosphide (IUPAC titles) (640)+TX, phosphorus [CCN]+TX, Duocide (1341)+TX, potassium arsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside (1390)+TX, sodium arsenite [CCN]+TX, Cymag (444)+TX, fluorine Sodium acetate (fluoroacetate) (735)+TX, strychnine (745)+TX, thallium sulfate [CCN]+TX, Warfarin (851) and phosphorus Change zinc (640)+TX,
A kind of synergist, the synergist are selected from the group by following material composition：2- (2- Butoxyethoxies) ethyl pepper Base ester (IUPAC titles) (934)+TX, 5- (1,3- benzodioxole -5- bases) -3- hexyl hexamethylene -2- ketenes (IUPAC Title) (903)+TX, have nerolidol farnesol (replacement title) (324)+TX, MB-599 (research code) (498)+ TX, MGK 264 (research code) (296)+TX, Butacide (piperonyl butoxide) (649)+TX, Piprotal (piprotal) (1343)+TX, propyl isome (propyl isomer) (1358)+TX, S421 (research code) (724)+TX, increasing Effect dissipates (sesamex) (1393)+TX, sesasmolin (1394) and sulfoxide (1406)+TX,
A kind of animal repellant, the animal repellant are selected from the group by following material composition：Anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, Cupravit (171)+TX, diazinon (227)+TX, bicyclopentadiene (chemical name) (1069)+TX, Guanoctine (422)+TX, biguanides acetate (422)+TX, mercaptodimethur (530)+TX, pyridine -4- amine (IUPAC names Claim) (23)+TX, plug logical sequence (804)+TX, Landrin (trimethacarb) (840)+TX, zinc naphthenate [CCN] and ziram (856)+TX,
A kind of virucide, the virucide are selected from the group by following material composition：Imanin (imanin) (substitutes name Claim) [CCN] and Ribavirin (replacement title) [CCN]+TX,
A kind of wound protective agent, the wound protective agent are selected from the group by following material composition：Mercury oxide (512)+TX, pungent thiophene Ketone (octhilinone) (590) and methyl sulphur mattress spirit (802)+TX,
And the compound of bioactivity, the compound are selected from the group of following material composition：Azaconazole (60207-31- 0]+TX, bitertanol [70585-36-3]+TX, bromuconazole [116255-48-2]+TX, cyproconazole [94361-06-5]+TX, Difenoconazole [119446-68-3]+TX, olefin conversion [83657-24-3]+TX, epoxiconazole [106325-08-0]+TX, nitrile benzene Azoles [114369-43-6]+TX, Fluquinconazole [136426-54-5]+TX, Flusilazole [85509-19-9]+TX, Flutriafol [76674- 21-0]+TX, hexaconazole [79983-71-4]+TX, imazalil [35554-44-0]+TX, glyoxalin [86598-92-7]+TX, kind Bacterium azoles [125225-28-7]+TX, metconazole [125116-23-6]+TX, nitrile bacterium azoles [88671-89-0]+TX, pefurazoate [101903-30-4]+TX, penconazole [66246-88-6]+TX, prothioconazoles [178928-70-6]+TX, pyrifenox (pyrifenox) [88283-41-4]+TX, Prochloraz [67747-09-5]+TX, propiconazole [60207-90-1]+TX, simeconazoles (simeconazole) [149508-90-7]+TX, Tebuconazole [107534-96-3]+TX, fluorine ether azoles [112281-77-3]+TX, Triazolone [43121-43-3]+TX, triazolone [55219-65-3]+TX, fluorine bacterium azoles [99387-89-0]+TX, triticonazole [131983-72-7]+TX, the three phonetic alcohol of ring benzene [12771-68-5]+TX, Fenarimol [60168-88-9]+TX, fluorochlorobenzene are phonetic Pyridine alcohol [63284-71-9]+TX, bupirimate (bupirimate) [41483-43-6]+TX, Milcurb (dimethirimol) [5221-53-4]+TX, Milstem (ethirimol) [23947-60-6]+TX, dodemorph [1593-77-7]+TX, fenpropidin (fenpropidine) [67306-00-7]+TX, butadiene morpholine [67564-91-4]+TX, spiral shell Ring bacterium amine [118134-30-8]+TX, tridemorph [81412-43-3]+TX, cyprodinil [121552-61-2]+TX, phonetic bacterium Amine [110235-47-7]+TX, pyrimethanil (pyrimethanil) [53112-28-0]+TX, fenpiclonil [74738-17-3]+TX, Fludioxonil (fludioxonil) [131341-86-1]+TX, M 9834 (benalaxyl) [71626-11-4]+TX, furalaxyl (furalaxyl) [57646-30-7]+TX, metalaxyl [57837-19-1]+TX, R- metalaxyls [70630-17-0]+TX, furan acyl Amine [58810-48-3]+TX, Wakil (Oxadixyl) [77732-09-3]+TX, benomyl [17804-35-2]+TX, more bacterium Spirit [10605-21-7]+TX, debacarb (debacarb) [62732-91-6]+TX, furidazol [3878-19-1]+TX, thiophene benzene reach Azoles [148-79-8]+TX, chlozolinate (chlozolinate) [84332-86-5]+TX, sclex (dichlozoline) [24201-58-9]+TX, iprodione (Iprodione) [36734-19-7]+TX, myclozoline [54864-61-8]+TX, Procymidone (procymidone) [32809-16-8]+TX, vinclozolin (vinclozoline) [50471-44-8]+TX, pyridine Acyl bacterium amine (boscalid) [188425-85-6]+TX, carboxin [5234-68-4]+TX, first furan anilide [24691-80-3]+ TX, flutolanil (Flutolanil) [66332-96-5]+TX, mebenil [55814-41-0]+TX, oxycarboxin [5259- 88-1]+TX, pyrrole metsulfovax (penthiopyrad) [183675-82-3]+TX, thiophene methuroxam [130000-40-7]+TX, biguanides Salt [108173-90-6]+TX, dodine (dodine) [2439-10-3] [112-65-2] (free key)+TX, iminoctadine (iminoctadine) [13516-27-3]+TX, Fluoxastrobin [131860-33-8]+TX, mandestrobin [173662-97- 0]+TX, dimoxystrobin [149961-52-4]+TX, Enestroburin { Proc.BCPC, Int.Congr., Glasgow.2003,1,93 } + TX, fluoxastrobin [361377-29-9]+TX, methyl kresoxim-methyl [143390-89-0]+TX, SSF 126 [133408-50-1] + TX, trifloxystrobin [141517-21-7]+TX, orysastrobin [248593-16-0]+TX, ZEN 90160 [117428-22-5]+TX, Pyraclostrobin [175013-18-0]+TX, fervam [14484-64-1]+TX, 3- [5- (4- chlorphenyls) -2,3- dimethyl -3- Isoxazole alkyl] pyridine (SYP-Z048), Mancozeb [8018-01-7]+TX, maneb [12427-38-2]+TX, Carbatene [9006-42-2]+TX, antracole (propineb) [12071-83-9]+TX, plug logical sequence [137-26-8]+TX, zineb [12122-67-7]+TX, ziram [137-30-4]+TX, difoltan (captafol) [2425-06-1]+TX, captan [133-06-2]+TX, dichlofluanid [1085-98-9]+TX, ethofumesate (fluoroimide) [41205-21-4]+TX, sterilizing Pellet [133-07-3]+TX, Tolylfluanid [731-27-1]+TX, Bordeaux (bordeaux) mixture [8011-63-0]+TX, Kocide SD (copperhydroxid) [20427-59-2]+TX, copper chloride (copperoxychlorid) [1332-40-7]+ TX, copper sulphate (coppersulfat) [7758-98-7]+TX, cupric oxide (copperoxid) [1317-39-1]+TX, maneb Copper (mancopper) [53988-93-5]+TX, copper 8-hydroxyquinolinate (oxine-copper) [10380-28-6]+TX, dinocap (dinocap) [131-72-6]+TX, nitrothalisopropyl (nitrothal-isopropyl) [10552-74-6]+TX, Hinosan [17109-49-8]+TX, different rice blast net (iprobenphos) [26087-47-8]+TX, Isoprothiolane (isoprothiolane) [50512-35-1]+TX, phosdiphen (phosdiphen) [36519-00-3]+TX, gram bacterium phosphorus (pyrazophos) [13457- 18-6]+TX, methyl support chlorine phosphorus (tolclofos-methyl) [57018-04-9]+TX, diazosulfide (acibenzolar- S-methyl) [135158-54-2]+TX, anilazine [101-05-3]+TX, benzene metsulfovax [413615-35-7]+TX, blasticidin-S (blasticidin)-S [2079-00-7]+TX, chinomethionat (chinomethionat) [2439-01-2]+TX, chloroneb (chloroneb) [2675-77-6]+TX, Bravo [1897-45-6]+TX, cyflufenamid [180409-60-3]+TX, white urea Cyanogen [57966-95-7]+TX, dichlone (dichlone) [117-80-6]+TX, double chlorine zarilamid (diclocymet) [139920-32-4]+TX, diclomezin (diclomezine) [62865-36-5]+TX, botran (dicloran) [99-30-9] + TX, diethofencarb (diethofencarb) [87130-20-9]+TX, dimethomorph [110488-70-5]+TX, SYP-LI90 (Flumorph) [211867-47-9]+TX, Delan (dithianon) [3347-22-6]+TX, Guardian (ethaboxam) [162650-77-3]+TX, Grandox fumigant (etridiazole) [2593-15-9]+TX, Famoxate [131807-57-3]+TX, Fenamidone (fenamidone) [161326-34-7]+TX, fenoxanil (Fenoxanil) [115852-48-7]+TX, fentin (fentin) [668-34-8]+TX, ferimzone (ferimzone) [89269-64-7]+ TX, fluazinam (fluazinam) [79622-59-6]+TX, fluopicolide (fluopicolide) [239110-15-7]+TX, sulphur Bacterium amine (flusulfamide) [106917-52-6]+TX, fenhexamid [126833-17-8]+TX, Fu Sai get (fosetyl- Aluminium) [39148-24-8]+TX, hymexazol (hymexazol) [10004-44-1]+TX, Propineb [140923-17- 7]+TX, IKF-916 (match seat goes out (Cyazofamid)) [120116-88-3]+TX, kasugarnycin (kasugamycin) [6980- 18-3]+TX, methasulfocarb (methasulfocarb) [66952-49-6]+TX, metrafenone [220899-03-6]+TX, Pencycuron (pencycuron) [66063-05-6]+TX, phthalide [27355-22-2]+TX, Polyoxin (polyoxins) [11113-80- 7]+TX, probenazole (probenazole) [27605-76-1]+TX, hundred dimension prestige (propamocarb) [25606-41-1]+TX, Iodine quinazolone (proquinazid) [189278-12-4]+TX, happy quinoline ketone (pyroquilon) [57369-32-1]+TX, quinoline oxygen Spirit [124495-18-7]+TX, Quintozene [82-68-8]+TX, sulphur [7704-34-9]+TX, tiadinil [223580-51- 6]+TX, triazoxide (triazoxide) [72459-58-6]+TX, tricyclazole [41814-78-2]+TX, triforine [26644- 46-2]+TX, valida [37248-47-8]+TX, zoxamide (zoxamide) (RH7281) [156052-68-5]+TX, Mandipropamid (mandipropamid) [374726-62-2]+TX,
And SDHI inhibitor, the SDHI inhibitor are selected from the group consisted of
([494793-67-8], (N- [2- (1,3- dimethylbutyl) phenyl] -5- is fluoro- by US 7538073 for fluorine azoles bacterium aniline 1,3- dimethyl -1H- pyrazole-4-carboxamides)+TX, furametpyr ([123572-88-3] (the chloro- N- of 5- (1,3- dihydros -1,1,3- Trimethyl -4- isobenzofuran-bases) -1,3- dimethyl -1H- pyrazole-4-carboxamides)+TX, pyrrole metsulfovax (US 5747518, [183675-82-3], (N- [2- (1,3- dimethylbutyls) -3- thienyls] -1- methyl -3- (trifluoromethyl) -1H- pyrazoles -4- Formamide)+TX, biphenyl pyrrole bacterium amine (US7329633, [581809-46-3], (N- (3 ', 4 '-two chloro- 5- fluorine [1,1 '-hexichol Base] -2- bases) -3- (difluoromethyl) -1- methyl isophthalic acid H- pyrazole-4-carboxamides)+TX, different piperazine draw praise (US 7598395, [881685-58-1] (2yn- isomers 3- (difluoromethyl) -1- methyl-N- [(1RS, 4SR, 9RS) -1,2,3,4- four Hydrogen -9- isopropyl -1,4- methanol naphthalene -5- bases] pyrazole-4-carboxamide and 2anti- isomers 3- (difluoromethyl) -1- first The mixing of base-N- [(1RS, 4SR, 9SR) -1,2,3,4- tetrahydrochysene -9- isopropyl -1,4- methanol naphthalene -5- bases] pyrazole-4-carboxamide Thing)+TX, fluorine azoles ring bacterium amine (EP 1480955B1, [874967-67-6] (2 cis-isomers 2 '-[(1RS, 2RS) -1, 1 '-two ring propyl- 2- yls] -3- (difluoromethyl) -1- methylpyrazoles -4- anilino-s formyl and 2 trans-isomers 2 ' - The mixture of [(1RS, 2SR) -1,1 '-two ring propyl- 2- yls] -3- (difluoromethyl) -1- methylpyrazole -4- anilino- formyls)+ TX, fluxapyroxad (US 8008232, [907204-31-3] (3- (difluoromethyl) -1- methyl-N- (3 ', 4 ', 5 '-trifluoros [1,1 '-diphenyl] -2- bases) -1H- pyrazole-4-carboxamides)+TX, solatenol (WO 2007/048556 (3- difluoromethyls - 1- methyl isophthalic acid H- pyrazoles -4- carboxylic acids (9- dichloro methylene -1,2,3,4- tetrahydrochysenes -1,4- methanol-naphthalene -5- bases)-acid amides)+TX, chemical combination Thing 3- (difluoromethyl)-N- methoxyl group -1- methyl-N- [1- methyl -2- (2,4,6- trichlorophenyls) ethyl] pyrazole-4-carboxamide (described in WO 2010/063700)+TX, thiophene fluorine bacterium amine (thifluzamide) (US 5045554, [130000-40-7] (N- [2,6- bis- bromo- 4- (trifluoromethoxy) phenyl] -2- methyl -4- (trifluoromethyl) -5- thiazole carboxamides)+TX, pyridine acyl bacterium Amine (US 5589493, [188425-85-6 (the chloro- N- of 2- (4 '-chlorine [1,1 '-diphenyl] -2- bases)-Niacinamide)+TX, Oxycarboxin ([5259-88-1] (5,6- dihydro -2- Methyl-N-phenyl -1,4- oxathiin -3- formamides 4,4- Dioxide)+TX, carboxin ([5234-68-4] (5,6- dihydro -2- Methyl-N-phenyl-Isosorbide-5-Nitraes-oxathiin -3- Formamide)+TX, fluopyram (US7572818, [658066-35-4]), (N- [2- [3- chloro- 5- (trifluoromethyl) -2- pyrroles Piperidinyl] ethyl] -2- (trifluoromethyl) benzamide)+TX, fluorine mepronil ([24691-80-3], (2- Methyl-N-phenyl -3- furans Mutter formamide, phenol bacterium fluorine comes), US 4093743, number of registration 66332-96-5 (N- [3- (1- methyl ethoxies) phenyl] -2- (three Methyl fluoride) benzamide)+TX, mebenil ([55814-41-0], (2- methyl-N- [3- (1- methyl ethoxies) phenyl] benzene first Acid amides)+TX and benodanil ([15310-01-7], (the iodo- N- phenylbenzamaides of 2-)+TX；
And compound [(3S, 4R, 4aR, 6S, 6aS, 12R, 12aS, 12bS) -3- [(cyclopropyl carbonyl) epoxide] -1,3, 4,4a, 5,6,6a, 12,12a, 12b- decahydro -6,12- dihydroxy -4,6a, 12b- trimethyl -11- oxygen -9- (3- pyridine radicals) - 2H, 11H naphtho- [2,1-b] pyrans simultaneously [3,4-e] pyrans -4- bases] methyl-cyclopropane formic acid esters [915972-17-7]+TX, 1, 3,5- trimethyls-N- (2- methyl isophthalic acids-oxygen propyl group)-N- [3- (2- methyl-propyls) -4- [fluoro- 1- methoxyl groups -1- (three of 2,2,2- tri- Methyl fluoride) ethyl] phenyl] -1H- pyrazole-4-carboxamides [926914-55-8]+TX and 4- oxygen -4- [(2- phenylethyls) ammonia Base]-butyric acid (is disclosed in WO 2010/137677)+TX.
The registration number for referring to chemical abstracts see, for example [3878-19-1] in the bracket after active component.More than The hybrid combination thing of description is known.When active component is included in " pesticides handbook (The Pesticide Manual) " [pesticides handbook-global overview (The Pesticide Manual-A World Compendium)； 13rd edition；Write：C.D.S. Tom woods (TomLin)；British Crop protective committee (The Pesticide Manual-A World Compendium；Thirteenth Edition；Editor:C.D.S.TomLin；The British Crop Protection Council)] in when, they above for specific compound in round parentheses give entry number under It is described in the handbook；For example, compound " abamectin " describes under entry number (1).To specific chemical combination more than When thing adds " [CCN] ", the compound discussed is included in " agricultural chemicals common name outline (Compendium of Pesticide Common Names) " in, the outline can obtain on the internet：[A.Wood (Wood)；Agricultural chemicals common name outline, copyright 1995-2013]；Such as compound " acetyl worm nitrile " is in the Internet addresshttp://www.alanwood.net/pesticides/ acetoprole.htmlUnder be described.
Largely be above in above-mentioned active component by so-called " common name ", related " ISO common names " or Another " common name " for using on rare occasion refers to.If title is not " common name ", then for specific chemical combination Thing gives the property of the title used as replacement in round parentheses；In this case, using IUPAC titles, IUPAC/ Chemical Abstracts names, " chemical name ", " traditional title ", " compound name " or " research code ", or if both Not using one of these titles, also without use " common name ", then use " replacement title ".
Compound with Formula I and the active component of above-mentioned active component selected from table 1 to 168 and V1 to V26 are mixed Compound includes a kind of compound selected from table 1 to 130 and a kind of above-mentioned active component, is preferably at from 100:1 to 1: 6000 blending ratio, especially from 50:1 to 1:50, more particularly it is in from 20:1 to 1:20 ratio, in addition more specifically from 10:1 to 1:10, very especially from 5:1 and 1:5, especially preferably from 2:1 to 1:What 2 ratio provided, and from 4:1 To 2:1 ratio is equally preferable, is especially in 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, Or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 4:75, or 1: 6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750 ratio. The ratio that these blending ratios are by weight.
Mixture described above can be used in the method for control harmful organism, and this method is included one kind containing as above The composition of the mixture of description is applied in harmful organism or its environment, except one kind by operation or therapy for handling people Or method and the diagnostic method for human or animal body implementation of animal body.
Retouched comprising the compound selected from table 1 to 168 and V1 to V26 with Formula I and one or more as more than The mixture for the active component stated can be applied for example in the form of a kind of single " ready-mix ", be mixed with the sprinkling of combination Thing (mixture is made up of the independent preparation of these single-activity compositions) (such as a kind of " bucket mix formulation ") is applied, and is worked as Combined when being applied in a manner of a kind of order (that is, after one in the period of another appropriateness is short, such as a few houres or several days) Applied using these independent active components.Using the chemical combination selected from these of table 1 to 168 and V1 to V26 with Formula I The order of thing and above-mentioned active component is not vital for implementing the present invention.
Biological example：
Example B1：Extra large spodoptera (Egyptian cotton leafworm)
Test compound is administered in 24 orifice plates and and agar with pipette from 10'000ppm DMSO stock solutions Mixed.Lactuca sativa seeds are placed on the agar and close the porous plate with another piece of flat board for also including agar.7 days it Afterwards, root absorbs the compound and lettuce has grown into lid flat board.These leaf lettuces are switched into lid flat board now In.Noctua ovum is aspirated through the plastic formwork on one piece of moist gel marking paper and its flat board closed.Infect 6 days it Afterwards, relative to untreated samples, for the death rate, Antifeeding Effects and growth inhibition evaluate sample.
Following compound gives these three classification (death rate, Antifeeding Effects or growths at 12.5ppm test rate Suppress) at least one at least 80% effect：
V20.02, V20.01, V16.02, V12.02, V16.01, V12.01 and V12.03
Example B2：Extra large spodoptera (Egyptian cotton leafworm)：
Cotton leaf disk is placed on the agar in 24 hole microtiter plates and molten with being laid in from 10'000ppm DMSO The water-based test solution prepared in liquid is sprayed.After drying, leaf disk is infected with five L1 phase larvas.Infect After 3 days, these samples are assessed for the death rate.
Following compound obtains at least 80% death rate under 200ppm rate of application：
Following compound obtains at least 80% control under 200ppm rate of application：
V14.01、V12.18、V16.08、V20.02、V16.02、V12.20、V12.02、V16.01、V12.01、V7.11、 V12.03, V25.03 and V7.09
Example B3：Diamondback moth (Plutella xylostella) (diamondback moth (Diamond back moth))：
The 24 hole microtiter plates with man-made feeds are water-based with being prepared from 10'000ppm DMSO stock solutions Test solution is handled by liquid relief.After drying, (10 to 15/hole) are infected to each plate with L2 phases larva.Invade Dye is assessed these samples after 5 days for the death rate.
Following compound obtains at least 80% death rate under 200ppm rate of application：
V14.01、V16.08、V20.08、V20.02、V16.09、V16.03、V16.07、V16.02、V12.02、 V16.01, V12.01, V7.11, V12.03, V13.05, V25.03 and V7.09
Example B4：Chrysomelid in cucumber strip (corn rootworm)：
The 24 hole microtiter plates with man-made feeds are water-based with being prepared from 10'000ppm DMSO stock solutions Test solution is handled by liquid relief.After drying, (6 to 10/ hole) is infected to each plate with L2 phases larva.Infect 5 After it, compared to untreated samples, sample is assessed for the death rate and growth inhibition.
Following compound gives at least one in two classifications (death rate or growth inhibition) under 200ppm rate of application At least 80% effect：
V14.01、V12.18、V16.08、V20.02、V16.09、V16.03、V16.07、V16.02、V12.20、 V12.02, V12.01, V7.11, V12.03, V13.05, V25.03 and V7.09.
Example B5：Black peach aphid (green peach aphid worm)：
Sunflower leaf disk is placed on the agar in 24 hole microtiter plates and laid in from 10'000ppm DMSO The water-based test solution prepared in solution is sprayed.After drying, by the aphid colony of these leaf disk mixed ages Infect.After infecting 6 days, these samples are assessed for the death rate.
Following compound obtains at least 80% death rate under 200ppm rate of application：
V14.01、V16.08、V20.08、V16.09、V16.03、V16.07、V16.02、V12.20、V12.02、 V14.05, V16.01, V12.17, V12.01, V7.11, V12.03, V25.03 and V7.09.
Example B6：Black peach aphid (green peach aphid worm)：
The root of the pea seedling infected by the aphid colony of mixed age is placed directly in from 10'000ppm DMSO In the water-based test solution prepared in stock solution.Seedling is placed in test solution after 6 days, for the death rate to these Sample is assessed.
Following compound obtains at least 80% death rate under 24ppm test rates：
V16.08、V20.08、V16.09、V16.03、V16.07、V12.20、V12.02、V14.05、V12.17、 V12.01 and V12.03.
Example B7：Black peach aphid (green peach aphid worm)：
Test compound from 10'000ppm DMSO stock solutions is administered to 24 hole microtitrations by pipette Mixed in plate and with sucrose solution.These flat boards are closed with the Parafilm films of stretching.A kind of 24 holes are moulded Material template is seated on the flat board and will be directly seated on the Parafilm films by the pea seedling infected.This is passed through The flat board infected is closed with gel blots paper (gel blotting paper) with other plastic formwork, and is then fallen Put.After infecting 5 days, these samples are assessed for the death rate.
Following compound obtains at least 80% death rate under 12ppm test rate：
V12.20, V12.02, V14.05, V16.01, V12.17, V12.01, V7.11, V12.03 and V7.09
Example B8：Onion thrips (onion thrips)：
Sunflower leaf disk is placed on the agar in 24 hole microtiter plates and laid in from 10'000ppm DMSO The water-based test solution prepared in solution is sprayed.After drying, the thrips by these leaf disks with a mixed age Population is infected.After infecting 6 days, these samples are assessed for the death rate.
Following compound obtains at least 80% death rate under 200ppm rate of application：
V12.01, V12.03 and V7.09
Example B9：Frankliniella occidentalis (western classical architecture)：
Sunflower leaf disk is placed on the agar in 24 hole microtiter plates and with from 10'000DMSO stock solutions The water-based test solution of middle preparation is sprayed.After drying, the flower thrips kind by these leaf disks with a mixed age Group infects.After infecting 7 days, these samples are assessed for the death rate.
Following compound obtains at least 80% death rate under 200ppm rate of application：
V12.02
Example B10：Bemisia tabaci (cotton aleyrodid)：
Cotton leaf disk is placed on the agar in 24 hole microtiter plates and molten with being laid in from 10'000ppm DMSO The water-based test solution prepared in liquid is sprayed.After drying, leaf disk is infected with adult aleyrodid.It is incubated 6 days Afterwards, these samples are checked for the death rate.
Following compound obtains at least 80% death rate under 200ppm rate of application：
V12.20, V12.02, V12.01, V13.05, V25.03 and V7.09.
Example B11：T.urticae Koch (Tetranychus urticae)：
Beans leaf disk on agar in 24 hole microtiter plates is prepared with from 10'000ppm DMSO stock solutions Water-based test solution sprayed.After drying, these leaf disks are infected with the mite population of a mixed age.Infect After 8 days, these samples are assessed for the death rate of mixed population (flowing platform).
Following compound obtains at least 80% death rate under 200ppm rate of application：
V14.01, V12.18, V20.08 and V16.02.
Example B12：Aedes aegypti (yellow fever mosquito)：
Larvicide, activity is contacted/ingests, treatment
10 to 15 albopictus larvaes (L2) are placed in 96 hole microtiter plates together with a kind of nutritional blend.By testization Compound pipette, extract is into this some holes.After 2 day time is incubated, insect is commented for the death rate and growth inhibition Estimate.
Following compound is given under 5ppm test rate at least one in the two classifications (death rate or growth inhibition) At least 80% individual effect：
V12.01。

Claims (5)

1. a kind of compound with Formula I,
A-B (I),
Wherein A is group A6.1
Wherein
G36It is N-R55, oxygen or sulphur；
R55It is C1-C4Alkyl；
G26It is nitrogen or methine；And
R54It is halogen, C1-C4Haloalkyl, C1-C4Halogenated alkylthio, C1-C4Halogenated alkyl sulfonyl, O (C1-C4Haloalkyl), SF5, phenylcarbonyl group sulfenyl, sulfydryl or C1-C4Alkoxy carbonyl；
Wherein arrow represents to be attached to group B point；And
B is group B7.1, B9.1 and B11.1
Wherein m is 0,1 or 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo cycloalkanes Base, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R42It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkane Base, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Wherein m is 0,1 or 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo cycloalkanes Base, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R44It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkane Base, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
Wherein m is 0,1 or 2；
R45It is C1-C4Alkyl, C1-C4Haloalkyl, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkyl, C3-C6Halo cycloalkanes Base, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；And
R46It is C1-C4Alkyl, C1-C4Haloalkyl, C1-C3Halogenated alkoxy, C3-C6Cycloalkyl, C3-C6Cycloalkyl-C1-C4Alkane Base, C3-C6Halogenated cycloalkyl, C2-C6Alkenyl, C2-C6Haloalkenyl group or C2-C6Alkynyl；
Together with acceptable salt, enantiomter, diastereoisomer and dynamic isomer in the agrochemicals of these compounds.
2. the compound according to claim 1 with Formula I, wherein in group A6.1
R54It is C1-C4Haloalkyl；
G36It is N-C1-C4Alkyl, oxygen or sulphur；And
G26It is nitrogen or methine；
In group B7.1
M is 2；
V82It is nitrogen or methine；
R41It is C1-C4Alkyl；And
R42It is C1-C4Haloalkyl；
In group B9.1
M is 2；
V81It is nitrogen or methine,
R43It is C1-C4Alkyl；And
R44It is C1-C4Haloalkyl；
And in group B11.1
M is 2；
R45It is C1-C4Alkyl；And
R46It is C1-C4Haloalkyl.
3. one kind kills insect, mite killing, kills nematode or kills mollusk composition, said composition is killed insect, mite killing comprising one, killed Nematode kills the compound according to claim 1 with Formula I of mollusk effective dose and a kind of suitable use In the carrier or diluent of the compound.
4. a kind of method resisted and control harmful organism, this method includes to kill insect, mite killing, and kill nematode or killing mollusk The compound according to claim 1 with Formula I of effective dose or the one kind for including the compound with Formula I Composition is applied to place where harmful organism, harmful organism, or is applied to easily by the plant of pest infestation, except one kind It is used for by operation or therapy outside the method for handling human body or animal body and the diagnostic method implemented to human body or animal body.
5. a kind of be used to protect the method that plant propagation material is attacked from harmful organism, this method is included with according to claim The place that the compositions-treated propagating materials or the propagating materials described in 3 are planted.
CN201480043333.0A 2013-07-02 2014-06-19 There are two rings or tricyclic heterocyclic with sulfur-bearing substituent for killing harmful organism activity Active CN105431433B (en)

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Citations (2)

* Cited by examiner, † Cited by third party
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WO2012086848A1 (en) * 2010-12-24 2012-06-28 Sumitomo Chemical Company, Limited Fused heterocyclic compound and use for pest control thereof
WO2013018928A1 (en) * 2011-08-04 2013-02-07 Sumitomo Chemical Company, Limited Fused heterocyclic compound and use thereof for pest control

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ES8401486A1 (en) * 1981-11-10 1983-12-01 Wellcome Found New imidazo[4,5-c]pyridine derivatives, processes for their preparation and pharmaceutical formulations containing such compounds.

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012086848A1 (en) * 2010-12-24 2012-06-28 Sumitomo Chemical Company, Limited Fused heterocyclic compound and use for pest control thereof
WO2013018928A1 (en) * 2011-08-04 2013-02-07 Sumitomo Chemical Company, Limited Fused heterocyclic compound and use thereof for pest control

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