Pyrazole compound and application thereof

Abstract

The invention discloses a pyrazole compound and application thereof. The structure of the pyrazole compound is shown as a general formula I, wherein the definition of each substituent group in a # imgabs0 # formula is shown in the specification; also disclosed in the specification are their use as insecticidal and acaricidal agents and animal parasite control agents.

Description

Technical Field

[0001] The invention relates to a pyrazole compound, in particular to a novel pyrazole compound and application thereof. Background Art

[0002] Patent CN105073735A relates to a halogen-substituted pyrazole derivative as a pest control agent, and specifically discloses the following structures: KC1 (compound number: Ic-205) and KC2 (compound number: Ic-206)

[0003]

[0004] In the prior art, there is no report on the compound represented by the general formula I of the present invention and its insecticidal activity. In addition, compared with the prior art, the compound of the present invention has higher insecticidal activity. Summary of the invention

[0005] The object of the present invention is to provide a pyrazole compound with better insecticidal and acaricidal activity and its application. The pyrazole compound can be used to prepare drugs for preventing and controlling pests and acarids in agriculture and other fields, and can be used to prepare drugs for controlling animal parasites in the field of veterinary medicine.

[0006] In order to achieve the purpose of the invention, the present invention provides the following technical solutions:

[0007] A pyrazole compound, as shown in general formula I:

[0008]

[0009] In the general formula I:

[0010] X is selected from CH or N;

[0011] R 1 Selected from H or CN;

[0012] R 2 Selected from CNCH 2 -、CNCH 2 CH 2 -、CNCH 2 CH 2 CH 2 -、CNCH 2 CH 2 CH 2 CH 2 -, propargyl, cyclopropylmethyl or

[0013] R 3 Selected from vinyl, C 3 -C 6 Cycloalkyl, C1 -C 4 Alkoxy C 1 -C 3 Alkyl or

[0014] Y 1 , Y 2 , Y 3 , Y 4 , Y 5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, halogenated C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio or halogenated C 1 -C 6 Alkylthio;

[0015] or a stereoisomer of the compound of formula I;

[0016] or a salt of a compound of formula I;

[0017] or a salt of a stereoisomer of a compound of formula I.

[0018] In a possible implementation, in the general formula I,

[0019] X is selected from CH or N;

[0020] R 1 Selected from H or CN;

[0021] R 2 Selected from CNCH 2 -、CNCH 2 CH 2 -、CNCH 2 CH 2 CH 2 -、CNCH 2 CH 2 CH 2 CH 2 -, propargyl, cyclopropylmethyl or

[0022] R 3 Selected from vinyl, C 3 -C 4 Cycloalkyl, C 1 -C 3 Alkoxy C 1-C 2 Alkyl or

[0023] Y 1 , Y 2 , Y 3 , Y 4 , Y 5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C 1 -C 4 Alkyl, halogenated C 1 -C 4 Alkyl, C 1 -C 4 Alkoxy, halogenated C 1 -C 4 Alkoxy, C 1 -C 4 Alkylthio or halogenated C 1 -C 4 Alkylthio;

[0024] or a stereoisomer of the compound of formula I;

[0025] or a salt formed by a compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid;

[0026] or a salt formed by a stereoisomer of a compound of formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

[0027] In a possible implementation, in the general formula I,

[0028] X is selected from CH or N;

[0029] R 1 Selected from H or CN;

[0030] R 2 Selected from CNCH 2 -、CNCH 2 CH 2 -、CNCH 2 CH 2 CH 2 -、CNCH 2 CH 2 CH 2 CH 2 -, propargyl, cyclopropylmethyl or

[0031] R 3 Selected from vinyl, C 3 -C 4 Cycloalkyl, C 1 -C 2 Alkoxy C 1 -C 2 Alkyl or

[0032] Y 1 , Y 2 , Y 3 , Y 4 , Y 5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C 1 -C 3 Alkyl, halogenated C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halogenated C 1 -C 3 Alkoxy, C 1 -C 3 Alkylthio or halogenated C 1 -C 3 Alkylthio;

[0033] or a stereoisomer of the compound of formula I;

[0034] or a salt formed by a compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid;

[0035] or a salt formed by a stereoisomer of a compound of formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

[0036] In a possible implementation, in the general formula I,

[0037] X is selected from CH or N;

[0038] R 1 Selected from H or CN;

[0039] R 2 Selected from CNCH 2 -、CNCH 2 CH 2 -、CNCH 2 CH2 CH 2 -、CNCH 2 CH 2 CH 2 CH 2 -, propargyl, cyclopropylmethyl or

[0040] R 3 Selected from vinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH 3 OCH 2 -、CH 3 CH 2 OCH 2 -、CH 3 CH 2 CH 2 OCH 2 -、(CH 3 ) 2 CHOCH 2 -、CH 3 CH 2 CH 2 CH 2 OCH 2 -、(CH 3 ) 3 COCH 2 -、CH 3 OCH 2 CH 2 -、CH 3 CH 2 OCH 2 CH 2 -、CH 3 CH 2 CH 2 OCH 2 CH 2 -、CH 3 CH 2 CH 2 CH 2 OCH 2 CH 2 -or

[0041] Y 1 , Y 2 , Y 3 , Y 4 , Y 5Each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio or 2,2,2-trifluoroethylthio;

[0042] or a stereoisomer of the compound of formula I;

[0043] or a salt formed by the compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid;

[0044] or a salt formed by a stereoisomer of the compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

[0045] In the definitions of the compounds of the general formula given above, the terms used generally represent the following substituents:

[0046] Halogen: refers to fluorine, chlorine, bromine or iodine.

[0047] Alkyl: straight-chain or branched-chain alkyl, such as methyl, ethyl, n-propyl, isopropyl or different butyl, pentyl or hexyl isomers.

[0048] Cycloalkyl: refers to substituted or unsubstituted cyclic alkyl, such as cyclopropyl, cyclopentyl or cyclohexyl; substituents such as methyl, halogen, etc.

[0049] Halogenated alkyl: straight-chain or branched-chain alkyl, on which the hydrogen atoms can be partially or completely substituted by halogen, such as chloromethyl, dichloromethyl, trichloromethyl, bromomethyl, dibromomethyl, tribromomethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, etc.

[0050] Alkoxy: straight-chain or branched-chain alkyl, bonded to the structure through an oxygen atom, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.

[0051] Haloalkoxy: The hydrogen atoms on the alkoxy group may be partially or completely substituted by halogen, for example, monochloromethoxy, dichloromethoxy, trichloromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2,2,2-trifluoroethoxy, etc.

[0052] Alkoxyalkyl: alkyl-O-alkyl-, such as CH 3 OCH 2 -、CH 3 CH 2 OCH 2 -、CH 3 CH 2 CH 2 OCH 2 -、(CH 3 ) 2 CHOCH 2 -、CH 3 CH 2 CH 2 CH 2 OCH 2 -、(CH 3 ) 3 COCH 2 -、CH 3 OCH 2 CH 2 -、CH 3 CH 2 OCH 2 CH 2 -、CH 3 CH 2 CH 2 OCH 2 CH 2 -、CH 3 CH 2 CH 2 CH 2 OCH 2 CH 2 -wait.

[0053] Alkylthio: A straight or branched alkyl group connected to the structure via a sulfur atom bond, such as methylthio, ethylthio, etc.

[0054] Haloalkylthio: The hydrogen atoms on the alkylthio group may be partially or completely substituted by halogen, for example chloromethylthio, difluoromethylthio, trifluoromethylthio, 2,2,2-trifluoroethylthio and the like.

[0055] Propargyl: CH≡C-CH 2 -.

[0056] Vinyl: CH 2 =CH-.

[0057] Some of the compounds of general formula I of the present invention are shown below, but the present invention is by no means limited to these compounds.

[0058]

[0059] Table 1: In general formula I, when X = N and R 1 =CN, R 2 or R 3 See Table 1 for different substituents, and the representative compounds are numbered 1.1-1.76.

[0060] Table 1

[0061]

[0062]

[0063] In the general formula I, when X=N and R 1 =H, the substituent R 2 or R 3 Consistent with Table 1 , the representative compound numbers are 2.1-2.76, corresponding to 1.1-1.76 in Table 1 , respectively.

[0064] In the general formula I, when X=CH and R 1 =CN, the substituent R 2 or R 3 Consistent with Table 1 , the representative compound numbers are 3.1-3.76, corresponding to 1.1-1.76 in Table 1 , respectively.

[0065] In the general formula I, when X=CH and R 1 =H, the substituent R 2 or R 3 Consistent with Table 1 , the representative compound numbers are 4.1-4.76, corresponding to 1.1-1.76 in Table 1 , respectively.

[0066] The present invention also provides a method for preparing the above pyrazole compounds, as follows (unless otherwise specified, the groups in the formula have the same definitions as above, wherein LG = Cl, Br or I):

[0067]

[0068] The compound of formula VI can be prepared by reacting the compound of formula IX with the compound of formula VIII in a suitable solvent, a base and a palladium catalyst at a temperature ranging from 40°C to the boiling point of the solvent for 0.5-48 hours using conventional methods.

[0069] In a possible implementation, the palladium catalyst includes: one or more of palladium acetate, palladium chloride, tetrakis(triphenylphosphine)palladium, tris(dibenzylideneacetone)dipalladium, 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride, 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride dioxymethane complex, bis(benzonitrile)palladium dichloride, and 1,4-bis(diphenylnitrile)butanepalladium dichloride.

[0070] The compound of general formula VI is reacted with an acyl chloride reagent to prepare a compound of general formula V.

[0071] In a possible implementation, the acyl chlorination agent includes: one or more of thionyl chloride, oxalyl chloride, phosgene, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride or triphosgene.

[0072] Route 1: The compound of formula V is reacted with the compound of formula IV in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula III; the compound of formula III is reacted with the compound of formula II (alkylating agent or acylating agent) in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula I.

[0073] Route 2: The compound of formula IV is reacted with the compound of formula II in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula VII; the compound of formula VII is reacted with the compound of formula V in a suitable solvent at a temperature ranging from -10°C to the boiling point of the solvent for 0.5-48 hours to obtain the compound of formula I.

[0074] In a possible implementation, the solvents for the reactions involved in Route 1 and Route 2 include: aromatic hydrocarbons such as benzene, toluene, and xylene; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; halogenated hydrocarbons such as chloroform and dichloromethane; esters such as methyl acetate and ethyl acetate; ethers such as tetrahydrofuran, dioxane, diethyl ether, and 1,2-dimethoxyethane; and polar solvents such as water, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, and dimethyl sulfoxide. One or more of the above.

[0075] In a possible implementation, the reactions involved in Scheme 1 and Scheme 2 can be carried out in the presence of a base, which includes: an organic base such as trimethylamine, triethylamine, pyridine, DBU, 4-dimethylaminopyridine, N,N-diisopropylmethylamine, N,N-diisopropylethylamine, an alkali metal hydride such as sodium hydride and potassium hydride, an alkali metal hydroxide such as sodium hydroxide and potassium hydroxide, an alkaline earth metal hydroxide such as calcium hydroxide, an alkali metal carbonate such as sodium carbonate and potassium carbonate, an alkali metal bicarbonate such as sodium bicarbonate, and a metal alkoxide such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-butoxide, or more.

[0076] The intermediate compound of formula IX can be prepared by a known method, for example, by referring to the method reported in WO2021239835 or WO2017055414. The compound of formula II and the compound of formula IV are usually commercially available or can be prepared by conventional methods.

[0077] The embodiment of the present invention also provides the use of the above pyrazole compounds in the preparation of insecticides and / or acaricides.

[0078] In one possible implementation, the insecticide is used to control one or more of the following insects:

[0079] beetles (Coleopteran), for example Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum, Epilachnavigintioctomaculata, Agriotes ogurae fuscicollis, Anomala rufocuprea, Leptinotarsa ​​decemlineata, Diabrotica spp., Monochamus alternatus endai, Lissorhoptrus oryzophilus, Lyctus bruneus;

[0080] Pests of the order of the Lepidopteran, for example, Lymantria dispar, Malacosoma neustria, Pieris rapae crucivora, Spodoptera litura, Mamestra brassicae, Chilo suppressalis, Ostrinia nubilalis, Cadra cautella, Adoxophyes honmai, Cydia pomonella, Agrotis segetum, Galleria mellonella, Plutella xylostella, Heliothis virescens, Phyllocnistis citrella;

[0081] Pests from the order of the Hemipterous, for example, Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspisyanonensis, Myzus persicas, Aphis pomi, Aphis gossypii, Lipaphis erysimi, Stephanitis nashi, Nezara spp., Trialeurodes vaporariorum, Pshylla spp.;

[0082] Pests of the order Thysanoptera, e.g. Thrips palmi, Franklinella occidentalis;

[0083] Orthopteran pests, such as African mole cricket (Gryllotalpa Africana), African migratory locust (Locusta migratoria);

[0084] Pests of the order Blattaria, such as Blattella germanica, Periplaneta americana, Reticulitermes speratus, Coptotermes formosanus;

[0085] Pests of the order Diptera, such as Musca domestica, Aedes aegypti, Delia platura, Culex pipiens pallens, Anopheles sinensis, Culex tritaeniorhynchus, Liriomyza trifolii, etc.

[0086] In a possible implementation, the acaricide is used to control one or more of the following mites: Tetranychus cinnabarinus, Tetrahychus urticae, Panonychus citri, Aculops pelekassi, Tarsonemus spp., etc.

[0087] In a possible implementation, the insecticide and / or acaricide is used to control one or several of Mythimna separata, Plutella xylostella, Tetranychus cinnabarinus.

[0088] The embodiment of the present invention also provides an insecticide preparation or an acaricide preparation, which contains the above-mentioned pyrazole compound as an active ingredient and also contains one or more auxiliary materials.

[0089] In a possible implementation, the insecticide preparation or acaricide preparation is selected from the following dosage forms: solution, emulsion, wettable powder, granular wettable powder, suspension, powder, foam, paste, tablet, granule, aerosol, natural agent impregnated with active compound, synthetic agent impregnated with active compound, microcapsule, seed coating, preparation equipped with combustion device (the combustion device may be chimney and mist cylinder, tank and coil, etc.) and ULV (cold fog, hot fog), etc. These insecticide preparations or acaricide preparations or animal parasite control agents can be prepared by known methods, for example, by mixing the active component with a filler (e.g., liquid diluent or carrier, liquefied gas diluent or carrier, solid diluent or carrier), and optionally with a surfactant (i.e., emulsifier and / or dispersant and / or foaming agent) and the like.

[0090] In a possible implementation, the auxiliary material includes one or more of the following: a filler (such as a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), a surfactant (such as an emulsifier and / or a dispersant and / or a foaming agent), a binder, and a colorant;

[0091] Liquid diluents or carriers may include, for example, aromatic hydrocarbons (xylene, toluene, alkylnaphthalene, etc.), chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons (e.g., chlorobenzene, vinyl chloride, methylene chloride, etc.), aliphatic hydrocarbons (e.g., cyclohexane or paraffin (e.g., mineral oil fractions)), alcohols (e.g., butanol, ethylene glycol, and ethers or esters thereof, etc.), ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.), strong polar solvents (e.g., dimethylformamide, dimethyl sulfoxide), water, etc. When water is used as the extender, for example, an organic solvent may be used as a cosolvent;

[0092] Liquefied gaseous diluents or carriers may include those that exist in gaseous form at atmospheric pressure and temperature, for example, propane, nitrogen, carbon dioxide, and aerosol propellants such as halogenated hydrocarbons;

[0093] Solid diluents may include crushed natural minerals (e.g., kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, etc.) and crushed synthetic minerals (e.g., finely dispersed silicic acid, alumina and silicates, etc.);

[0094] Emulsifiers and / or foaming agents may include nonionic and anionic emulsifiers [e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty acid alcohol ethers (e.g., alkylaryl polyethylene glycol ethers), alkyl sulfonates, alkyl sulfates, and aryl sulfonates], and albumin hydrolyzates, etc.;

[0095] Dispersants may include lignin sulfite waste liquor and methylcellulose;

[0096] Binders may include carboxymethyl cellulose, natural or synthetic polymers (eg, gum arabic, polyvinyl alcohol, polyvinyl acetate, etc.).

[0097] Colorants may include inorganic pigments (such as iron oxide, titanium oxide and Prussian blue, etc.), organic dyes such as alizarin dyes, azo dyes or metal phthalocyanine dyes; and trace elements such as iron salts, manganese salts, boron salts, copper salts, cobalt salts, molybdenum salts or zinc salts.

[0098] Furthermore, the pyrazole compounds of the invention may be present as a mixture with a synergist, which need not be active itself but rather is a compound which enhances the activity of the active compound.

[0099] In a possible implementation, the amount of the pyrazole compound contained in the insecticide formulation or the acaricide formulation is 0.1 to 99% by weight, and optionally 0.5 to 90% by weight.

[0100] The present invention also provides an insecticide composition or acaricide composition, which comprises a mixture of the above-mentioned pyrazole compound and other active compounds (such as insecticides, baits, disinfectants, acaricides, nematicides, fungicides, growth regulators, herbicides, etc.). The mixture can be provided in the form of a bulk drug, or in the form of a commercially available useful preparation or in a use form prepared from the preparation.

[0101] An embodiment of the present invention also provides a method for controlling agricultural or forestry pests and / or mites, which comprises the following steps: applying an effective dose of a material to the pests and mites to be controlled or their growth medium, wherein the material is selected from one or more of the following groups: the above-mentioned pyrazole compounds, the above-mentioned insecticide preparations or miticide preparations, the above-mentioned insecticide compositions or miticide compositions.

[0102] The present invention also provides the use of the pyrazole compounds in the preparation of an animal parasite control agent. In the veterinary field, that is, in veterinary science, the pyrazole compounds of the present invention can be effectively used to combat a variety of harmful animal parasites, particularly endoparasites and ectoparasites.

[0103] In one possible implementation, the animal parasites include one or more of the following:

[0104] From the order of the Anoplurida, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp. and Solenopotes spp.; in particular, representative examples are Linognathus setosus and Solenopotes capillatus;

[0105] From the order Mallophaga (Linognathus vituli, Linognathus ovillus, Linognathus oviformis, Linognathus pedalis, Linognathus stenopsis, Haematopinus asini macrocephalus, Haematopinus eurysternus, Haematopinus suis, Pediculus humanus capitis, Pediculus humanus corporis, Phylloxera vastatrix, Phthirus pubis) and from the suborders Amblycerina and Ischnocerin, for example, Trimenopon spp., Menopon spp., Trinoton spp. spp.), Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina spp., Trichodectes spp., and Felicola spp.; in particular, representative examples are Bovicola bovis, Bovicola ovis, Bovicola limbata, Damalina bovis, Trichodectes canis, Felicola subrostratus, Bovicola caprae, Lepikentron ovis, Werneckiella equi;

[0106] From the order Diptera and its suborders Nematocerina and Brachycerina, for example, Aedes spp., Anopheles spp., Culex spp., Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp., Culicoides spp., Chrysops spp., Odagmia spp., Wilhelmia spp., Hybomitra spp., Atylotus spp. spp.), Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp.), Gasterophilus spp., Hippobosca spp., Lipoptena spp., Melophagus spp., Rhinoestrus spp., Tipula spp.; in particular, representative examples are Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora erythrocephala, Chrysozona pluvialis, Culex five-bandedquinquefasciatus), Culexpipiens, Culex tarsalis, Fannia canicularis, Sarcophagacarnaria, Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmiaornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanus atratus), Tabanus sudeticus, Hybomitra ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis, Haematopotaitalica, Musca autumnalis, Musca domestica, Haematobiairritans irritans, Haematobia irritans exigua, Haematobiastimulans, Hydrotaea irritans, Hydrotaea albipuncta, Chrysomyachloropyga, Chrysomya bezziana, Oestrus ovis, Hypoderma bovis, Hypoderma lineatum), Przhevalskiana silenus, Dermatobia hominis, Melophagus ovinus, Lipoptena capreoli, Lipoptenacervi, Hippobosca variegata, Hippoboscaequina), Gasterophilusintestinalis, Gasterophilus haemorroidalis, Gasterophilusinterrnis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum, Braula coeca;

[0107] From the order of the Siphonapterida, for example, Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.; in particular, representative examples are Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tungapenetrans, Xenopsylla cheopis;

[0108] From the order of the Heteropterida, for example, Cimex spp., Triatomaspp., Rhodnius spp., Panstrongylus spp.;

[0109] From the order of the Blattarida, for example, Blatta orientalis, Periplaneta americana, German cockroach, Supella spp. (for example, Suppella longipalpa);

[0110] From the order of the Acari (or Acarina), the orders Metastigmata and Mesostigmata, for example, Argas spp., Ornithodorus spp., Otobius spp., Ixodes spp., Amblyomma spp., Rhipicephalus (Boophilus) spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Dermanyssus spp., Rhipicephalus spp. (the original genus of heteroparasitic mites), Ornithonyssus spp. spp.), Pneumonyssus spp., Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., Varroa spp., Acarapis spp.; in particular, representative examples are Argas persicus, Argas reflexus, Ornithodorus moubata, Otobius megnini), Rhipicephalus (Boophilus) microplus, Rhipicephalus (Boophilus) decoloratus, Rhipicephalus (Boophilus) annulatus, Rhipicephalus (Boophilus) calceratus, Hyalomma anatolicum, Hyalomma aegypticum, Hyalomma marginatum, Hyalomma transiens, Rhipicephalus evertsi, Ixodes ricinus, Ixodes hexagonus, Ixodes canisuga, Ixodes pilosus, Ixodes rubrumrubicundus), Ixodes scapularis, Ixodesholocyclus, Haemaphysalis concinna, Haemaphysalis punctata, Haemaphysalis cinnabarina, Haemaphysalis otophila, Haemaphysalis leachi, Haemaphysalis longicorni, Dermacentor marginatus, Dermacentor reticulatus, Dermacentor pictus, Dermacentor albipictus, Dermacentor andersoni, Dermacentor variabilis, Hyalomma mauritanicum, Rhipicephalus sanguineus, Rhipicephalus sac bursa), African fanhead tick (Rhipicephalus appendiculatus), Cape fanhead tick (Rhipicephalus capensis), Turan fanhead tick (Rhipicephalus turanicus), Rhipicephalus zambeziensis, American flower tick (Amblyomma americanum), colored flower tick (Amblyomma variegatum, Amblyomma maculatum, Hebrew flower tick (Amblyomma hebraeum), Kayan flower tick (Amblyomma cajennense), Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, Varroajacobsconi;

[0111] From the orders Actinedida (Prostigmata) and Acaridida (Astigmata), for example, Acarapis spp., Cheyletiella spp., Ornithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp., Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp. spp.), Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.; in particular, Cheyletiella yasguri, Cheyletiella blakei, Demodex canis, Demodex bovis, Demodex ovis, Demodex caprae, Demodex equi, Demodex caballi, Demodex suis, Neotrombicula autumnalis, Neotrombicula desaleli, Neoschonegastia xerothermobia, Trombicula akamushi, Otodectes cynotis, Notoedres cati, Sarcoptes canis, Sarcoptes bovis, Sarcoptes ovis, Sarcoptes rupicaprae (= S.caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum, Acarapis woodi;

[0112] Nematodes, such as Meloidogyne incognita, Bursaphelenchus xylophilus, Aphelenchoides besseyi, Heteroderaglycines, Pratylenchus spp., etc.

[0113] Arthropods, worms and malarial parasites that attack animals. Controlling arthropods, worms and / or malarial parasites reduces mortality in domestic animals and improves the productivity (meat, milk, wool, hides, eggs and honey) and health of the animals.

[0114] In a possible implementation, the animal parasite control agent is used to control one or more of cat fleas and American dog ticks.

[0115] In one possible implementation, the animals include one or more of the following: agricultural animals, such as cattle, sheep, goats, horses, pigs, donkeys, camels, buffaloes, rabbits, chickens, turkeys, ducks, geese, farmed fish, bees, etc.; also include pets known as companion animals, such as dogs, cats, caged birds, ornamental fish; also include animals used for experiments, such as hamsters, guinea pigs, rats and mice, etc.

[0116] The embodiment of the present invention further provides an animal parasite control agent, which contains the above-mentioned pyrazole compound as an active component and one or more auxiliary materials.

[0117] In one possible implementation, the animal parasite control agent is selected from the following dosage forms: tablets, capsules, drinks, drinkable medicines, granules, ointments and pills, suppositories, injections (muscular, subcutaneous, intravenous, intraperitoneal, etc.), ointments, aerosols, non-pressure sprays (such as pump sprays and atomized sprays).

[0118] In a possible implementation, the amount of the above active ingredient contained in the animal parasite control agent is 1 to 80% by weight.

[0119] The present invention also provides an animal parasite control composition, which includes a mixture of the above-mentioned pyrazole compound and other animal parasite control active compounds (such as acaricides, insecticides, parasiticides, antimalarial protozoa, etc.). The mixture can be provided in the form of a bulk drug, or in the form of a commercially available preparation or a use form prepared from the preparation.

[0120] The embodiment of the present invention also provides a method for controlling animal parasites, which comprises the following steps: applying an effective dose of a material to the animal parasites to be controlled or their growth medium, wherein the material is selected from one or more of the following groups: the above-mentioned pyrazole compounds; the above-mentioned animal parasite control agent; the above-mentioned animal parasite control composition. For example: enteral administration using tablets, capsules, potions, drinkable medicines, granules, ointments, pills, suppositories; non-enteral administration based on skin administration, such as injection (muscle, subcutaneous, intravenous, intraperitoneal, etc.), implantation, nasal administration, including bathing or soaking, spraying, pouring, dripping, washing and dusting, and administration by using model products containing active compounds, such as collars, ear tags, tags, leg braces, nets, markers, etc. The active compounds of the present invention have low toxicity and can be safely used in warm-blooded animals.

[0121] Beneficial Effects

[0122] The pyrazole compounds of the present invention have unexpectedly excellent insecticidal and acaricidal effects, and also exhibit suitable control effects on toxic pests, and have no phytotoxicity to cultivated crop plants. In addition, the compounds of the present invention can be used to control a variety of pests, such as harmful piercing-sucking insects, chewing insects and other plant parasitic pests, stored grain pests, sanitary pests, etc., and can be used to disinfect and kill them. DETAILED DESCRIPTION

[0123] The following specific examples are used to further illustrate the present invention, but the present invention is by no means limited to these examples. (Unless otherwise noted, all raw materials used are commercially available)

[0124] Synthesis Example

[0125] According to the synthetic route described above, different raw material compounds can be used to prepare the compounds represented by the general formula I of the present invention, which are further described as follows:

[0126] Example 1: Preparation of Compound 1.1

[0127]

[0128] Step 1: Synthesis of intermediate 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile

[0129] 1-Amino-1-cyclopropylcarbonitrile hydrochloride (2.08 g, 17.52 mmol), bromoacetonitrile (4.20 g, 35.03 mmol), N,N-diisopropylethylamine (6.79 g, 52.55 mmol) and 10 mL of toluene were added to a 100 mL reaction bottle, and the reaction solution was brought to reflux and continued to react for 3 hours. After the reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness under reduced pressure, 50 mL of ethyl acetate and 50 mL of water were added for extraction, and the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.25 g of an oily substance, namely the intermediate 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile.

[0130] Step 2: Synthesis of intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinic acid

[0131] To a 50 mL reaction flask, 5-bromo-2-chloronicotinic acid (0.73 g, 3.09 mmol) and 2'-methyl-5'-(perfluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4'-(trifluoromethyl)-2'H-1,3'-bipyrazole (1.30 g, 2.83 mmol) were added and dissolved in 13 mL of N,N-dimethylformamide with stirring. Potassium carbonate (1.17 g, 8.47 mmol) and 2.5 mL of water were added. The reaction mixture was degassed under nitrogen for 10 minutes, then tetrakis(triphenylphosphine)palladium (0.16 g, 0.14 mmol) was added and then degassed under nitrogen for another ten minutes. The reaction mixture was stirred at 80 °C for 6 hours. The reaction solution was then poured into 30 mL of water and acidified to pH 2 with 2M HCl. The mixture was extracted twice between ethyl acetate and water. The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give a residue. The residue was purified by column chromatography to give 0.93 g of intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinic acid (yellow solid). The NMR and mass spectrometry data of the intermediate are as follows:

[0132] 1 H NMR (600 MHz, DMSO-d 6)δ13.92(s,1H),8.97(s,1H),8.95(d,1H),8.69(s,1H),8.54(d,1H),3.84(s,3H).ESI-MS(m / z):488.02[MH] - .

[0133] Step 3: Synthesis of intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinoyl chloride

[0134] 2-Chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinic acid (18.25 g, 37.27 mmol), thionyl chloride (13.30 g, 111.81 mmol) and 100 mL of toluene were added to a 250 mL reaction bottle, and the temperature was raised to 110°C for reaction for 3 hours. The reaction solution was concentrated under reduced pressure to obtain 18.63 g of an oily substance, namely the intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinyl chloride.

[0135] Step 4: Synthesis of compound 1.1

[0136] 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile (1.25 g, 10.31 mmol), triethylamine (2.09 g, 20.62 mmol) and 50 mL of dichloromethane were added to a 100 mL reaction bottle, and 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinoyl chloride (5.24 g, 10.31 mmol) was added dropwise under ice bath stirring; after the addition was completed, the reaction solution was warmed to room temperature and the reaction was continued for 4 hours. After the reaction was completed by TLC monitoring, the reaction solution was concentrated to dryness under reduced pressure, 150 mL of ethyl acetate and 150 mL of water were added for extraction, the organic phase was washed with saturated sodium bicarbonate solution and saturated brine in turn, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by column chromatography to obtain 4.93 g of white solid, i.e., the target compound 1.1 (white solid). The NMR and mass spectrometry data of compound 1.1 are as follows:

[0137] 1 H NMR(600MHz,Chloroform-d)δ8.75(d,1H),8.24(s,1H),8.11(d,2H),4.56(s,2H),3.85(s,3H),1.64(m,2H),0.87(m,2H).ESI-MS(m / z):593.08[M+H] + .

[0138] Example 2: Preparation of Compound 1.3

[0139]

[0140] Step 1: Synthesis of intermediate 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide

[0141] Referring to the synthesis method of step 4 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinyl chloride and 1-amino-1-cyclopropylnitrile hydrochloride were used as raw materials to prepare the intermediate 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide (white solid). The nuclear magnetic resonance and mass spectrometry data of the intermediate are as follows:

[0142] 1 H NMR (600 MHz, Acetonitrile-d 3 )δ8.74(d,1H),8.32(d,2H),8.12(d,1H),7.67(s,1H),3.76(s,3H),1.62-1.56(m,2H),1.37-1.32(m,2H).ESI-MS(m / z):553.92[M+H] + .

[0143] Step 2: Synthesis of compound 1.3

[0144] Add 60% NaH (0.03 g, 0.78 mmol) and 10 mL THF to a 25 mL reaction bottle, cool to 0-5 °C in an ice bath; add 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl) nicotinamide (0.29 g, 0.52 mmol) under stirring, keep stirring at 0-5 °C for 30 minutes, then add 4-bromobutyronitrile (0.15 g, 1.01 mmol); warm the reaction solution to room temperature, continue stirring and react for 3 hours. After the reaction is completed by TLC monitoring, add 20 mL of water to quench the reaction. Add 50 mL of ethyl acetate and 50 mL of water to the reaction solution for extraction, wash the organic phase with saturated brine, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. The residue is purified by column chromatography to obtain 0.25 g of a white solid, i.e., the target compound 1.3. The NMR and mass spectrometry data of compound 1.3 are as follows:

[0145] 1 H NMR (600 MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 70:30, δ8.90-8.78 (m, 1H), 8.61 (d, 1H), 8.45 (s, 1.4 / 2H), 8.27 (d, 0.6 / 2H), 3.99-3.48 (m, 5H), 2.67 (t, 0.7 / 1H), 2.51 (t, 0.7 / 1H), 2.22 (s, 0.7 / 1H), 2.1 2(t,0.7 / 1H),1.79(d,0.6 / 2H),1.62(t,0.3 / 1H),1.55-1.52(m,1.4 / 1H),1.39(t,0.3 / 1 H),1.24(t,0.3 / 1H),1.20-1.12(m,0.3 / 1H),0.90-85(m,2H).ESI-MS(m / z):621.91[M+H] + .

[0146] Example 3: Synthesis of Compound 1.5

[0147]

[0148] Referring to the synthesis method of step 2 of Example 2, compound 1.5 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and bromoacetonitrile as raw materials. The NMR and mass spectrometry data of compound 1.5 are as follows:

[0149] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 57:43, δ8.87 (s, 0.43 / 1H), 8.85 (s, 0.57 / 1H), 8.61 (s, 1H), 8.45 (s, 1H), 8.39 (s, 0.43 / 1H), 8.25 (s, 0.57 / 1H), 4.59 (s, 0.43 / 2H), 4.36 (s, 0.43 / 2H), 4.15 (s, 1.14 / 2H), 3.82 (s, 3H), 2.93 (s, 0.57 / 1H), 2.88 (s, 0.43 / 1H), 1.76-1.66 (m, 2H), 1.33-0.78 (m, 2H). ESI-MS (m / z): 592.08 [M+H] + .

[0150] Example 4: Synthesis of Compound 1.6

[0151]

[0152] Referring to the synthesis method of step 2 of Example 2, compound 1.6 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and bromomethylcyclopropane as raw materials. The NMR and mass spectrometry data of compound 1.6 are as follows:

[0153] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 67:33, δ8.86 (s, 0.33 / 1H), 8.83 (s, 0.67 / 1H), 8.62 (s, 1H), 8.46 (s, 1H), 8.38 (s, 0.33 / 1H), 8.25 (s, 0.67 / 1H), 3.82 (s, 3H), 3.31 (d, 0.66 / 2H), 3.16 (d, 1.34 / 2H), 1.82-1.51 (m, 4H), 1.19-1.09 (m, 1H), 0.70-0.18 (m, 4H). ESI-MS (m / z): 608.11 [M+H] + .

[0154] Example 5: Synthesis of Compound 1.7

[0155]

[0156] Referring to the synthesis method of step 2 of Example 2, compound 1.7 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and acryloyl chloride as raw materials. The NMR and mass spectrometry data of compound 1.7 are as follows:

[0157] 1 H NMR (600MHz, Methanol-d 4 )δ8.80(d,1H),8.59(s,1H),8.43(s,1H),8.25(d,1H),6.94(dd,1H),6.47(d,1H),6.01 (d,1H),3.82(s,3H),1.94-1.96(m,2H),1.62-1.59(m,2H).ESI-MS(m / z):608.08[M+H] + .

[0158] Example 6: Synthesis of Compound 1.8

[0159]

[0160] Referring to the synthesis method of step 2 of Example 2, compound 1.8 (yellow solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and cyclopropylcarbonyl chloride as raw materials. The NMR and mass spectrometry data of compound 1.8 are as follows:

[0161] 1 HNMR (600MHz, Methanol-d 4 )δ8.75(s,1H),8.57(s,1H),8.42(s,1H),8.18(s,1H),3.82(s,3H),2.38(m,1H),2.04-1.98 (m,2H),1.72-1.68(d,2H),1.16-1.12(m,2H),1.08-1.03(m,2H).ESI-MS(m / z):622.09[M+H] + .

[0162] Example 7: Synthesis of Compound 1.13

[0163]

[0164] Referring to the synthesis method of step 2 of Example 2, compound 1.13 (yellow solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and ethoxyacetyl chloride as raw materials. The NMR and mass spectrometry data of compound 1.13 are as follows:

[0165] 1 HNMR (600MHz, Methanol-d 4 )δ8.83(dd,1H),8.66-8.62(m,1H),8.47(d,J=7.9Hz,1H),4.18(s,1H),3.83(d,3H),3.6 9(q,1H),3.34(s,1H),3.01(t,1H),2.44(q,1H),1.30(t,3H).ESI-MS(m / z):640.10[M+H] + .

[0166] Example 8: Synthesis of Compound 1.21

[0167]

[0168] Referring to the synthesis method of step 2 of Example 2, compound 1.21 (yellow solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and benzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 1.21 are as follows:

[0169] 1 H NMR (600MHz, Methanol-d 4 )δ8.56(d,1H),8.48(s,1H),8.32(s,1H),7.99(d,1H),7.61-7.58(m,2H),7.41-7.38(m,1 H),7.34(t,2H),3.83(s,3H),1.87-1.81(m,2H),1.59(d,2H).ESI-MS(m / z):658.35[M+H] + .

[0170] Example 9: Synthesis of Compound 1.24

[0171]

[0172] Referring to the synthesis method of step 2 of Example 2, compound 1.24 (yellow solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and p-fluorobenzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 1.24 are as follows:

[0173] 1 HNMR (600MHz, Methanol-d 4 )δ8.61(d,1H),8.51(s,1H),8.35(s,1H),8.03(d,1H),7.70-7.66(m,2H),7.09(t,2 H),3.83(s,3H),3.35(s,3H),1.84(s,2H),1.60(s,2H).ESI-MS(m / z):676.08[M+H] + .

[0174] Example 10: Synthesis of Compound 2.1

[0175]

[0176] Step 1: Synthesis of intermediate 2-(cyclopropyl)aminoacetonitrile

[0177] Referring to the synthetic method of step 1 in Example 1, cyclopropylamine and bromoacetonitrile were used as raw materials to prepare the intermediate 2-(cyclopropyl)aminoacetonitrile.

[0178] Step 2: Synthesis of compound 2.1

[0179] Referring to the synthesis method of step 4 of Example 1, the target compound 2.1 (white solid) was prepared using the intermediate 2-(cyclopropyl)aminoacetonitrile and 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinoyl chloride as raw materials. The NMR and mass spectrometry data of compound 2.1 are as follows:

[0180] 1 H NMR(600MHz,Chloroform-d)δ8.67(d,1H),8.18(s,1H),8.01(s,1H),7.80(d,1H),4.50 (s,2H),3.87(s,3H),3.02(m,1H),0.86(m,2H),0.76(m,2H).ESI-MS(m / z):568.83[M+H] + .

[0181] Example 11: Synthesis of Compound 2.3

[0182]

[0183] Step 1: Synthesis of intermediate 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide

[0184] Referring to the synthesis method of step 4 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinyl chloride and cyclopropylamine were used as raw materials to prepare the intermediate 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide (white solid). The nuclear magnetic resonance and mass spectrometry data of the intermediate are as follows:

[0185] 1 H NMR (600 MHz, Acetonitrile-d 3)δ8.70(d,1H),8.31(d,2H),8.05(d,1H),7.02(s,1H),3.75(s,3H),2.90-2. 81(m,1H),0.82-0.76(m,2H),0.64-0.58(m,2H).ESI-MS(m / z):529.07[M+H] + .

[0186] Step 2: Synthesis of compound 2.3

[0187] Referring to the synthesis method of step 2 of Example 2, compound 2.3 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and 4-bromobutyronitrile as raw materials. The NMR and mass spectrometry data of compound 2.3 are as follows:

[0188] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 90:10, δ8.79 (d, 0.90 / 1H), 8.77 (d, 0.10 / 1H), 8.60 (s, 0.90 / 1H), 8.59 (s, 0.10 / 1H), 8.44 (s, 1H), 8.25 (d, 0.90 / 1H), 8.21 (d, 0.10 / 1H), 3.82 (s, 3H), 3.73 (d, 1.80 / 2H), 3.31(d,0.20 / 2H),2.92-2.85(m,0.90 / 1H),2.84-2.78(m,0.10 / 1H),2.63(t,1.80 / 2H),2.45(t ,0.20 / 2H),2.19(t,0.20 / 2H),2.11(t,1.80 / 2H),0.87-0.62(m,4H).ESI-MS(m / z):596.11[M+H] + .

[0189] Example 12: Synthesis of Compound 2.5

[0190]

[0191] Referring to the synthesis method of step 2 of Example 2, compound 2.5 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and 3-bromopropyne as raw materials. The NMR and mass spectrometry data of compound 2.5 are as follows:

[0192] 1H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 90:10, δ8.80 (d, 1H), 8.62 (s, 0.90 / 1H), 8.60 (s, 0.1 / 1H), 8.45 (s, 0.90 / 1H), 8.44 (s, 0.10 / 1H), 8.18 (d, 1H), 4.38 (d, 1.80 / 2H), 4.00 (d, 0.20 / 2H), 2.99-2.91 (m, 1H), 2.80 (t, 0.1 / 1H), 2.71 (t, 0.9 / 1H), 1.02-0.64 (m, 4H). ESI-MS (m / z): 553.07 [M+H] + .

[0193] Example 13: Synthesis of Compound 2.7

[0194]

[0195] Referring to the synthesis method of step 2 of Example 2, compound 2.7 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and acryloyl chloride as raw materials. The NMR and mass spectrometry data of compound 2.7 are as follows:

[0196] 1 H NMR (600 MHz, DMSO-d 6 )δ8.89(s,1H),8.86(d,1H),8.63(s,1H),8.31(d,1H),7.03(dd,1H),6.29(dd,1H),5.95(dd,1H), 3.83(s,3H),3.01-2.95(m,1H),1.08-1.04(m,2H),0.72-0.68(m,2H).ESI-MS(m / z):569.07[M+H] + .

[0197] Example 14: Synthesis of Compound 2.8

[0198]

[0199] Referring to the synthesis method of step 2 of Example 2, compound 2.8 (yellow solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and cyclopropylcarbonyl chloride as raw materials. The NMR and mass spectrometry data of compound 2.8 are as follows:

[0200] 1 H NMR (600MHz, Methanol-d 4 )δ8.71(d,1H),8.57(s,1H),8.41(s,1H),8.08(d,1H),3.82(s,3H),3.05-3.00(m,1H),2.60-2.55(m,1H) ,1.20-1.16(m,2H),1.08-1.04(m,2H),0.98-0.95(m,2H),0.92-0.89(m,2H).ESI-MS(m / z):583.08[M+H] + .

[0201] Example 15: Synthesis of Compound 2.13

[0202]

[0203] Referring to the synthesis method of step 2 of Example 2, compound 2.13 (yellow solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and ethoxyacetyl chloride as raw materials. The NMR and mass spectrometry data of compound 2.13 are as follows:

[0204] 1 HNMR (600MHz, Methanol-d 4 )δ8.79(d,1H),8.60(s,1H),8.44(s,1H),8.24(d,1H),4.64(s,2H),3.83(s,3H),3.61( q,2H),2.83(tt,1H),1.22(t,3H),0.95(d,2H),0.76(t,2H).ESI-MS(m / z):615.19[M+H] + .

[0205] Example 16: Synthesis of Compound 2.21

[0206]

[0207] Referring to the synthetic method of step 2 of Example 2, compound 2.21 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and benzoyl chloride as raw materials.

[0208] The NMR and mass spectrometry data of compound 2.21 are as follows:

[0209] 1HNMR (600MHz, Methanol-d 4 )δ8.68(d,1H),8.54(s,1H),8.38(s,1H),8.14(d,1H),7.76(d,2H),7.54(t,1H),7.46(t,2 H),3.82(s,3H),3.12(tt,1H),0.91(d,2H),0.71-0.65(m,2H).ESI-MS(m / z):633.08[M+H] + .

[0210] Example 17: Synthesis of Compound 2.24

[0211]

[0212] Referring to the synthesis method of step 2 of Example 2, compound 2.24 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)nicotinamide and p-fluorobenzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 2.24 are as follows:

[0213] 1 HNMR (600MHz, Methanol-d 4 )δ8.71(d,1H),8.56(s,1H),8.40(s,1H),8.17(d,1H),7.86(dd,2H),7.21(t,2 H),3.82(s,3H),3.12(tt,1H),0.91(t,2H),0.67(d,2H).ESI-MS(m / z):651.09

[0214] [M+H] + .

[0215] Example 18: Synthesis of Compound 3.1

[0216]

[0217] Step 1: Synthesis of intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoic acid

[0218] Referring to the synthesis method of step 2 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4'-(trifluoromethyl)-2'H-1,3'-bipyrazole and 5-bromo-2-chlorobenzoic acid were used as raw materials to prepare 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoic acid (yellow solid). The nuclear magnetic resonance and mass spectrometry data of the intermediate are as follows:

[0219] 1 H NMR (600 MHz, DMSO-d 6 )δ13.63(s,1H),8.85(s,1H),8.57(s,1H),8.04(d,1H),7.83(dd,1H),7.59(d,1H),3.83(s,3H).ESI-MS(m / z):487.03[MH] - .

[0220] Step 2: Synthesis of 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride

[0221] Referring to the synthesis method of step 3 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoic acid was used as a raw material to prepare the intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride.

[0222] Step 3: Synthesis of compound 3.1

[0223] Referring to the synthesis method of step 4 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride and 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile were used as raw materials to prepare compound 3.1 (white solid). The NMR and mass spectrometry data of compound 3.1 are as follows:

[0224] 1H NMR(600MHz,Chloroform-d)δ8.19(s,1H),8.01(s,1H),7.76(s,1H),7.63(dd,1H),7.57(d,1H ),4.56(s,2H),3.84(s,3H),1.68-1.59(m,2H),1.27-1.26(m,2H).ESI-MS(m / z):592.08[M+H] + .

[0225] Example 19: Synthesis of Compound 3.2

[0226]

[0227] Step 1: Synthesis of 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide

[0228] Referring to the synthetic method of step 4 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride and 1-amino-1-cyclopropylnitrile hydrochloride were used as raw materials to prepare the intermediate 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide.

[0229] The NMR and mass spectrometry data of the intermediate are as follows:

[0230] 1 H NMR (600 MHz, Acetonitrile-d 3 )δ8.26(d,2H),7.74(d,1H),7.70(dd,1H),7.57(s,1H),7.51(d,1H),3.75 (s,3H),1.63-1.56(m,2H),1.51-1.32(m,2H).ESI-MS(m / z):553.07[M+H] + .

[0231] Step 2: Synthesis of compound 3.2

[0232] Referring to the synthesis method of step 2 of Example 2, compound 3.2 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and 3-bromopropionitrile as raw materials. The NMR and mass spectrometry data of compound 3.2 are as follows:

[0233] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 58:42, δ8.46 (s, 1H), 8.36 (s, 1H), 7.99 (s, 0.58 / 1H), 7.88 (s, 0.42 / 1H), 7.82 (s, 1H), 7.62 (d, 0.58 / 1H), 7.55 (d, 0.42 / 1H), 4.14 (s, 0.58 / 2H), 3.83 (s, 0.58 / 2H), 3.82 (s, 3H), 3.61 (s, 0.84 / 2H), 3.17-2.73 (m, 2H), 1.95-1.47 (m, 4H). ESI-MS (m / z): 606.10 [M+H] + .

[0234] Example 20: Synthesis of Compound 3.3

[0235]

[0236] Referring to the synthesis method of step 2 of Example 2, compound 3.3 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and 4-bromobutyronitrile as raw materials. The NMR and mass spectrometry data of compound 3.3 are as follows:

[0237] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 52:48, δ8.49 (s, 0.52 / 1H), 8.48 (s, 0.48 / 1H), 8.37 (s, 1H), 7.98 (d, 0.48 / 2H), 7.83-7.76 (m, 1.52 / 2H), 7.60 (d, 0.48 / 1H), 7.55 (d, 0.52 / 1H), 3.99 (s, 0.48 / 2H ),3.81(s,3H),3.61(s,0.48 / 2H),3.50-3.32(m,1.04 / 2H),2.66(t,0.96 / 2H),2.47(t,1.04 / 2H),2.22-2.06(m,2H),1.77(d,1H),1.58(d,2H),1.29(s,1H).ESI-MS(m / z):620.11[M+H] + .

[0238] Example 21: Synthesis of Compound 3.5

[0239]

[0240] Referring to the synthesis method of step 2 of Example 2, compound 3.5 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and 3-bromopropyne as raw materials. The NMR and mass spectrometry data of compound 3.5 are as follows

[0241] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 65:35, δ8.20 (s, 0.65 / 1H), 8.14 (s, 0.35 / 1H), 8.02 (s, 0.65 / 1H), 7.93 (s, 0.35 / 1H), 7.79 (s, 0.65 / 1H), 7.64-7.50 (m, 2H), 7.46 (d, 0.35 / 1H), 4.7 3(s,0.65 / 2H),4.17(s,0.65 / 2H),4.02(s,0.70 / 2H),3.86(s,1.05 / 3H),3.83(s,1.9 5 / 3H),2.44(s,1H),1.84-1.61(m,2H),0.92-0.74(m,2H).ESI-MS(m / z):591.09[M+H] + .

[0242] Example 22: Synthesis of Compound 3.6

[0243]

[0244] Referring to the synthesis method of step 2 of Example 2, compound 3.6 (yellow solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and bromomethylcyclopropane as raw materials. The NMR and mass spectrometry data of compound 3.6 are as follows:

[0245] 1 H NMR (600MHz, Methanol-d 4): The spectrum showed a mixture of rotamers in a ratio of about 66:34, δ8.51 (s, 0.66 / 1H), 8.48 (s, 0.34 / 1H), 8.38 (s, 0.66 / 1H), 8.37 (s, 0.34 / 1H), 7.91 (s, 0.34 / 1H), 7.80 (d, 0.34 / 1H), 7.78 (d, 0.66 / 1H), 7.76 (s, 0.66 / 1H), 7.60(d,0.34 / 1H),7.55(d,0.66 / 1H),3.81(s,3H),3.30(t,0.68 / 2H),3.13(t,1.32 / 2H),1.79-1.50(m,4H),1.15-1.12(m,1H),0.72-0.14(m,4H).ESI-MS(m / z):607.12[M+H] + .

[0246] Example 23: Synthesis of Compound 3.7

[0247]

[0248] Referring to the synthesis method of step 2 of Example 2, compound 3.7 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and acryloyl chloride as raw materials. The NMR and mass spectrometry data of compound 3.7 are as follows:

[0249] 1 H NMR(600MHz,Chloroform-d)δ8.16(s,1H),7.96(s,1H),7.64(d,1H),7.59(dd,1H),7.47(d,1H),6.86(dd,1 H),6.55(d,1H),5.95(d,1H),3.84(s,3H),1.86-1.81(m,2H),1.53-1.49(m,2H).ESI-MS(m / z):607.08[M+H] + .

[0250] Example 24: Synthesis of Compound 3.8

[0251]

[0252] Referring to the synthesis method of step 2 of Example 2, compound 3.8 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and cyclopropylcarbonyl chloride as raw materials. The NMR and mass spectrometry data of compound 3.8 are as follows:

[0253] 1 H NMR (600MHz, Methanol-d 4 )δ8.47(s,1H),8.35(s,1H),7.78(d,1H),7.75(dd,1H),7.48(d,1H),3.81(s,3H),2.27-2.22 (m,1H),1.93-1.87(m,2H),1.64-1.60(m,2H),1.06-1.01(m,4H).ESI-MS(m / z):621.10[M+H] + .

[0254] Example 25: Synthesis of Compound 3.21

[0255]

[0256] Referring to the synthesis method of step 2 of Example 2, compound 3.21 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and benzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 3.21 are as follows:

[0257] 1 H NMR (600MHz, Methanol-d 4 )δ8.36(s,1H),8.23(s,1H),7.53-7.48(m,4H),7.35(t,1H),7.29-7.23(m,3H) ,3.82(s,3H),1.87-1.82(m,2H),1.65-1.58(m,2H).ESI-MS(m / z):657.10[M+H] + .

[0258] Example 26: Synthesis of Compound 3.24

[0259]

[0260] Referring to the synthesis method of step 2 of Example 2, compound 3.24 (white solid) was prepared using 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and p-fluorobenzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 3.24 are as follows:

[0261] 1 H NMR (600 MHz, Methanol-d 4 )δ8.39(s,1H),8.26(s,1H),7.60(dd,2H),7.57-7.52(m,2H),7.28(d,1H),7.01(t, 2H),3.82(s,3H),1.88-1.80(m,2H),1.66-1.57(m,2H).ESI-MS(m / z):675.09[M+H] + .

[0262] Example 27: Synthesis of Compound 4.1

[0263]

[0264] Referring to the synthesis method of step 4 of Example 1, the target compound 4.1 (white solid) was prepared using the intermediate 2-(cyclopropyl)aminoacetonitrile and 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 4.1 are as follows:

[0265] 1 H NMR(600MHz,Chloroform-d)δ8.13(s,1H),7.92(s,1H),7.54(dd,1H),7.48(d,1H),7.46(d,1H),4.50(s ,2H),3.86(s,3H),2.99-2.94(m,1H),1.26-1.23(m,2H),0.70-0.67(m,2H).ESI-MS(m / z):567.91[M+H] + .

[0266] Example 28: Synthesis of Compound 4.2

[0267]

[0268] Step 1: Synthesis of 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide

[0269] Referring to the synthesis method of step 4 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride and cyclopropylamine were used as raw materials to prepare the intermediate 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide.

[0270] Step 2: Synthesis of compound 4.2

[0271] Referring to the synthetic method of step 2 of Example 2, compound 4.2 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and 3-bromopropionitrile as raw materials.

[0272] The NMR and mass spectrometry data of compound 4.2 are as follows:

[0273] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 90:10, δ8.48 (s, 0.90 / 1H), 8.45 (s, 0.10 / 1H), 8.35 (s, 0.90 / 1H), 8.34 (s, 0.1 / 1H), 7.82-7.70 (m, 2H), 7.54 (d, 0.90 / 1H), 7.49 (d, 0.10 / 1H), 3.96-3.76 (m, 1.80 / 2H), 3.82 (s, 3H), 3.54-3.48 (m, 0.20 / 2H), 3.01-2.64 (m, 3H), 0.88-0.59 (m, 4H). ESI-MS (m / z): 581.10 [M+H] + .

[0274] Example 29: Synthesis of Compound 4.5

[0275]

[0276] Referring to the synthesis method of step 2 of Example 2, compound 4.5 (brown solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and 3-bromopropyne as raw materials.

[0277] The NMR and mass spectrometry data of compound 4.5 are as follows:

[0278] 1 H NMR (600MHz, Methanol-d 4 ): The spectrum showed a mixture of rotamers in a ratio of about 84:16, δ8.49 (s, 0.84 / 1H), 8.47 (s, 0.16 / 1H), 8.36 (s, 0.84 / 1H), 8.35 (s, 0.16 / 1H), 4.37 (d, 1.68 / 2H), 3.97 (d, 0.32 / 2H), 3.82 (s, 1H), 2.97-2.91 (m, 1H), 2.76 (t, 0.16 / 1H), 2.68 (t, 0.84 / 1H), 1.02-0.60 (m, 4H). ESI-MS (m / z): 566.09 [M+H] + .

[0279] Example 30: Synthesis of Compound 4.7

[0280]

[0281] Referring to the synthesis method of step 2 of Example 2, compound 4.7 (yellow solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and acryloyl chloride as raw materials.

[0282] The NMR and mass spectrometry data of compound 4.7 are as follows:

[0283] 1 H NMR (600MHz, Methanol-d 4 )δ8.47(s,1H),8.35(s,1H),7.75-7.71(m,2H),7.47(d,1H),7.02(dd,1H),6.34(dd,1H),5.84(dd,1 H),3.81(s,3H),2.93-2.88(m,1H),1.02-0.98(m,2H),0.75-0.71(m,2H).ESI-MS(m / z):582.09[M+H] + .

[0284] Example 31: Synthesis of Compound 4.8

[0285]

[0286] Referring to the synthesis method of step 2 of Example 2, compound 4.8 (yellow solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and cyclopropanecarbonyl chloride as raw materials. The NMR and mass spectrometry data of compound 4.8 are as follows:

[0287] 1 H NMR (600 MHz, Methanol-d 4 )δ8.46(s,1H),8.34(s,1H),7.72-7.66(m,2H),7.44(d,1H),3.81(s,3H),3.00-2.91(m,1H),2.60-2.51(m, 1H),1.10-1.05(m,2H),1.04-0.99(m,2H),0.98-0.95(m,2H),0.86-0.81(m,2H).ESI-MS(m / z):596.10[M+H] + .

[0288] Example 32: Synthesis of Compound 4.21

[0289]

[0290] Referring to the synthetic method of step 2 of Example 2, compound 4.21 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide and benzoyl chloride as raw materials.

[0291] The NMR and mass spectrometry data of compound 4.21 are as follows:

[0292] 1 HNMR (600MHz, Methanol-d 4 )δ8.35(s,1H),8.23(s,1H),7.66(d,2H),7.60(d,1H),7.55(dd,1H),7.44(t,1H),7.36(t, 2H),7.32(d,1H),3.75(s,3H),0.85(d,2H),0.67-0.63(m,2H).ESI-MS(m / z):632.06[M+H] + .

[0293] Example 33: Synthesis of Compound 4.24

[0294]

[0295] Referring to the synthesis method in Step 2 of Example 2, compound 4.24 (white solid) was prepared using 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)benzamide and p-fluorobenzoyl chloride as raw materials. The NMR and mass spectrometry data of compound 4.24 are as follows:

[0296] 1 HNMR(600MHz,Methanol-d 4 )δ8.43(s,1H),8.30(s,1H),7.82-7.78(m,2H),7.68(d,1H),7.64(dd,1H),7.39(d,1H),7.15(t,2H),3.81(s,3H),3.09(tt,1H),2.01(s,3H),0.92-0.89(m,2H),0.72-0.68(m,2H).ESI-MS(m / z):650.09[M+H] + .

[0297] Biological activity assay

[0298] Example 34: Biological activity assay of Mythimna separata and Plutella xylostella

[0299] Insecticidal activity assay experiments were conducted on several insects using the compounds of the present invention. The assay method is as follows:

[0300] The test compound was dissolved in a mixed solvent of acetone / methanol (1:1) and then diluted with water containing 0.1% (wt) Tween 80 to the required concentration.

[0301] Using Mythimna separata and Plutella xylostella as targets, the activity assay was carried out by the Airbrush spraying method.

[0302] (1) Activity assay against Mythimna separata

[0303] Assay method: The corn leaves were cut into leaf segments 2 cm long. The pressure for Airbrush spraying treatment was 10 psi (equivalent to about 0.7 kg / cm 2 ), and both the front and back sides of each leaf segment were sprayed. The spraying volume of the test compound was 0.5 mL. After air-drying, 10 third-instar larvae were introduced into each treatment, and each treatment was repeated 3 times. After treatment, they were placed in an observation chamber at 25 °C and a relative humidity of 60-70% for cultivation. The number of surviving insects was investigated 3 days after treatment, and the mortality rate was calculated.

[0304] Some test results against Mythimna separata are as follows:

[0305] At a dosage of 0.625 mg / L, 3 days after administration, the mortality rates of compounds 1.1, 1.3, 1.5, 1.6, 1.7, 1.8, 1.13, 1.21, 1.24, 2.1, 2.3, 2.5, 2.7, 2.8, 2.13, 2.21, 2.24, 3.1, 3.2, 3.3, 3.5, 3.6, 3.7, 3.8, 3.21, 3.24, 4.1, 4.2, 4.5, 4.7, 4.8, 4.21, and 4.24 to armyworms were all above 90%.

[0306] (2) Determination of activity against Plutella xylostella

[0307] Test method: Use a punch to punch cabbage leaves into leaf discs with a diameter of 2 cm and use an Airbrush spray to treat them at a pressure of 10 psi (about 0.7 kg / cm 2 ), spray each leaf disc on both sides, with the spray volume of the test compound being 0.5 mL. After drying in the shade, 10 3rd instar larvae were inoculated for each treatment, and each treatment was repeated 3 times. After treatment, the leaves were placed in an observation room at 25°C and a relative humidity of 60-70% for cultivation. The number of surviving insects was investigated 3 days after the application, and the mortality rate was calculated.

[0308] Some of the test results on Plutella xylostella are as follows:

[0309] At a dosage of 0.625 mg / L, 3 days after administration, the mortality rates of compounds 1.1, 1.3, 1.5, 1.6, 1.7, 1.8, 1.13, 1.21, 1.24, 2.1, 2.3, 2.5, 2.7, 2.8, 2.13, 2.21, 2.24, 3.1, 3.2, 3.3, 3.5, 3.6, 3.7, 3.8, 3.21, 3.24, 4.1, 4.2, 4.5, 4.7, 4.8, 4.21, and 4.24 to Plutella xylostella were all above 90%.

[0310] Some compounds of the present invention and control compounds were selected for parallel comparison test of insecticidal activity against Plutella xylostella (3 days after application), and the determination method was the same as described above; the results are shown in Table 5:

[0311] Table 5 Parallel comparison test of insecticidal activity of some compounds of the present invention and control compounds against Plutella xylostella

[0312]

[0313]

[0314] Note: KC1 and KC2 in the table are compounds specifically disclosed in patent CN105073735A; KC3 and KC4 are reference compounds provided in this application. Reference compounds KC1, KC2, KC3 and KC4 can be obtained by referring to the methods of the embodiments of the present invention, and the raw materials can be prepared according to the methods of the embodiments of the present invention, or can be purchased or can be prepared according to conventional methods.

[0315] KC1: white solid. 1 H NMR(600MHz,Chloroform-d)δ8.18(s,1H),8.00(s,1H),7.70(d,1H),7.60(dd,1H),7.51(d,1H),3 .83(s,3H),2.91(q,2H),1.46(d,2H),1.27-1.25(m,2H),1.21(t,3H).ESI-MS(m / z):609.22[M+H] + .

[0316] KC2: white solid. 1 H NMR(600MHz,Chloroform-d)δ8.49(s,0.61 / 1H),8.48(s,0.39 / 1H),8.36(s,1H),7.93(s,0.39 / 1H),7.81(d,0.3 9 / 1H),7.78(d,0.61 / 1H),7.73(s,0.61 / 1H),7.61(d,0.39 / 1H),7.54(d,0.61 / 1H),6.09(m,0.39 / 1H),5.94(m,0. 61 / 1H),5.43(d,0.39 / 1H),5.36(d,0.61 / 1H),5.26(s,0.61 / 1H),5.24(s,0.61 / 1H),4.45(s,0.39 / 1H),4.17(s,0 .61 / 1H),3.91(s,1H),3.81(s,3H),1.58(s,2H),0.98(m,0.39 / 1H),0.88(m,0.61 / H).ESI-MS(m / z):593.14[M+H] + .

[0317] KC3: white solid. 1 H NMR (600MHz, Methanol-d 4)δ8.78(d,1H),8.59(s,1H),8.43(s,1H),8.20(d,1H),3.82(s,3H),3.81(s,3H),1.91-1.87(m,2H),1.62(t,2H).ESI-MS(m / z):612.10[M+H] + .

[0318] KC4: white solid. 1 H NMR (600MHz, Methanol-d 4 )δ8.79(d,1H),8.60(s,1H),8.44(s,1H),8.21(d,1H),4.22(q,2H),3.83(s, 3H),1.91-1.86(m,2H),1.61(t,2H),1.15(t,3H).ESI-MS(m / z):626.14[M+H] + .

[0319] In the embodiment of the present invention, by 1 , R 2 , R 3 , Y 1 , Y 2 , Y 3 , Y 4 , Y 5 As shown in Table 5, by comparing compounds 3.1, 3.5, 3.6 with the control compound KC2, by comparing compounds 3.7, 3.8 with the control compound KC1, and by comparing compounds 1.7, 1.8, 1.13 with the control compounds KC3, KC4, it can be seen that due to the R 2 Selected from CNCH 2 -、CNCH 2 CH 2 -、CNCH 2 CH 2 CH 2 -、CNCH 2 CH 2 CH 2 CH 2 -, propargyl, cyclopropylmethyl or And R 3 Selected from vinyl, C 3 -C 6 Cycloalkyl, C 1 -C 4 Alkoxy C 1 -C 3 Alkyl or and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, C 1 -C 6 Alkoxy, halogenated C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio or halogenated C 1 -C 6 The alkylthio group makes the compounds of the present invention have unexpectedly high insecticidal activity.

[0320] Example 35: Biological Activity Assay of Tetranychus cinnabarinus

[0321] The greenhouse mite killing activity of the compound of the present invention was determined as follows:

[0322] According to the solubility of the test compound, it is dissolved in acetone or dimethyl sulfoxide, and 50 mL of the test solution of the required concentration is prepared with 0.1% Tween 80 solution. The content of acetone or dimethyl sulfoxide in the solution shall not exceed 10%.

[0323] Take two true leaf bean seedlings and inoculate 30-40 adult cinnabarinus spider mites. After investigating the base number, use a handheld sprayer to spray the whole plant. Repeat 3 times for each treatment. After treatment, place them in a standard observation room. After 72 hours, investigate the number of surviving mites and calculate the mortality rate.

[0324] Some test results on adult Tetranychus cinnabarinus mites are as follows:

[0325] At a dosage of 1.25 mg / L, the mortality rates of compounds 1.1, 1.3, 1.5, 1.6, 1.7, 1.8, 1.13, 1.21, 1.24, 2.1, 2.3, 2.5, 2.7, 2.8, 2.13, 2.21, 2.24, 3.1, 3.2, 3.3, 3.5, 3.6, 3.7, 3.8, 3.21, 3.24, 4.1, 4.2, 4.5, 4.7, 4.8, 4.21, and 4.24 to adult cinnabarinus spider mites were all above 90%.

[0326] Example 36: Insecticidal test on cat fleas

[0327] 4 mg of the compound to be tested was dissolved in 40 mL of acetone to obtain an acetone solution with a concentration of 100 mg / L. 400 μL of the solution was applied to the bottom and sides of a culture dish with an inner diameter of 5.3 cm. After the acetone evaporated, a thin film of the compound of the present invention was formed on the inner wall of the culture dish. The inner wall of the culture dish used was 40 cm. 2 , the treatment dose is 1μg / cm 2 ; 10 adult cat fleas (mixed males and females) were placed therein, and the mixture was covered and stored in a constant temperature room at 25°C. The number of dead fleas after 72 hours was checked, and the mortality rate was calculated. The test was repeated 3 times. Test results: Compounds 1.1, 1.3, 1.5, 1.6, 1.7, 1.8, 1.13, 1.21, 1.24, 2.1, 2.3, 2.5, 2.7, 2.8, 2.13, 2.21, 2.24, 3.1, 3.2, 3.3, 3.5, 3.6, 3.7, 3.8, 3.21, 3.24, 4.1, 4.2, 4.5, 4.7, 4.8, 4.21, 4.24 showed a mortality rate of more than 70%.

[0328] Example 37: Insecticidal test on American dog tick

[0329] 4 mg of the compound to be tested was dissolved in 40 mL of acetone to obtain an acetone solution with a concentration of 100 mg / L. 400 μL of the solution was applied to the bottom and side surfaces of two culture dishes with an inner diameter of 5.3 cm. After the acetone evaporated, a thin film of the compound of the present invention was formed on the inner wall of the culture dish. The inner wall of the culture dish used was 40 cm. 2 , the treatment dose is 1μg / cm 2 . 10 first nymphs of American dog ticks (mixed males and females) were placed therein, two culture dishes were combined, the joints were sealed with tape to prevent escape, and the dishes were stored in a constant temperature chamber at 25°C. The number of dead insects after 24 hours was checked and the mortality rate was calculated. The test was repeated 3 times. Test results: Compounds 1.1, 1.3, 1.5, 1.6, 1.7, 1.8, 1.13, 1.21, 1.24, 2.1, 2.3, 2.5, 2.7, 2.8, 2.13, 2.21, 2.24, 3.1, 3.2, 3.3, 3.5, 3.6, 3.7, 3.8, 3.21, 3.24, 4.1, 4.2, 4.5, 4.7, 4.8, 4.21, 4.24 showed a mortality rate of more than 70%.

Claims

1. A pyrazole compound, characterized in that: The structure of the pyrazole compound is shown in general formula I: In the general formula I: X is selected from CH or N; R1 is selected from H or CN; R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or R3 is selected from vinyl, C3-C6 cycloalkyl, C1-C4 alkoxy, C1-C3 alkyl or Y1, Y2, Y3, Y4, and Y5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C6 alkyl, halogenated C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C1-C6 alkylthio, or halogenated C1-C6 alkylthio; or a stereoisomer of the compound of formula I; or a salt of a compound of formula I; or a salt of a stereoisomer of a compound of formula I.

2. The pyrazole compound according to claim 1, characterized in that In the general formula I: X is selected from CH or N; R1 is selected from H or CN; R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or R3 is selected from vinyl, C3-C4 cycloalkyl, C1-C3 alkoxy, C1-C2 alkyl or Y1, Y2, Y3, Y4, and Y5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, C1-C4 alkylthio, or halogenated C1-C4 alkylthio; or a stereoisomer of the compound of formula I; or a salt formed by a compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid; or a salt formed by a stereoisomer of a compound of formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

3. The pyrazole compound according to claim 2, characterized in that In the general formula I: X is selected from CH or N; R1 is selected from H or CN; R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or R3 is selected from vinyl, C3-C4 cycloalkyl, C1-C2 alkoxy, C1-C2 alkyl or Y1, Y2, Y3, Y4, and Y5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C3 alkyl, halogenated C1-C3 alkyl, C1-C3 alkoxy, halogenated C1-C3 alkoxy, C1-C3 alkylthio, or halogenated C1-C3 alkylthio; or a stereoisomer of the compound of formula I; or a salt formed by a compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid; or a salt formed by a stereoisomer of a compound of formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

4. The pyrazole compound according to claim 1, characterized in that In the general formula I: X is selected from CH or N; R1 is selected from H or CN; R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or R3 is selected from vinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH3OCH2-, CH3CH2OCH2-, CH3CH2CH2OCH2-, (CH3)2CHOCH2-, CH3CH2CH2CH2OCH2-, (CH3)3COCH2-, CH3OCH2CH2-, CH3CH2OCH2CH2-, CH3CH2CH2OCH2CH2-, CH3CH2CH2CH2OCH2CH2- or Y1, Y2, Y3, Y4, Y5 are each independently selected from hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio or 2,2,2-trifluoroethylthio; or a stereoisomer of the compound of formula I; or a salt formed by a compound of formula I and hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid; or a salt formed by a stereoisomer of a compound of formula I with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, butyric acid, valeric acid, trifluoroacetic acid, oxalic acid, malonic acid, methanesulfonic acid, 4-toluenesulfonic acid, malic acid, fumaric acid, lactic acid, maleic acid, salicylic acid, tartaric acid or citric acid.

5. Use of the pyrazole compound according to any one of claims 1 to 4 in the preparation of insecticides and / or acaricides.

6. The use according to claim 5, characterized in that: The insecticide and / or acaricide is used for preventing and controlling one or more of armyworm, diamondback moth, cinnabarinus spider mite, peach aphid and striped stem borer.

7. An insecticide preparation or acaricide preparation, characterized in that: The insecticide preparation or acaricide preparation contains the pyrazole compound according to any one of claims 1 to 4 as an active ingredient, and further contains one or more auxiliary materials; optionally, the amount of the pyrazole compound according to any one of claims 1 to 4 in the insecticide preparation or acaricide preparation is 0.1 to 99% by weight, and further optionally 0.5 to 90% by weight.

8. An insecticide composition or acaricide composition, characterized in that: A mixture comprising the pyrazole compound according to any one of claims 1 to 4 and other active compounds, wherein the other active compounds are selected from one or more of insecticides, baits, disinfectants, miticides, nematicides, fungicides, growth regulators, and herbicides.

9. A method for controlling agricultural or forestry pests and / or mites, characterized in that: Apply an effective dose of material to the pests and mites to be controlled or their growth medium, wherein the material is selected from one or more of the following groups: The pyrazole compound according to any one of claims 1 to 4; The insecticide preparation or acaricide preparation according to claim 7; The insecticide composition or acaricide composition according to claim 8.

10. Use of the pyrazole compound according to any one of claims 1 to 4 in the preparation of an animal parasite control agent.

11. The use according to claim 10, characterized in that: The animal parasite control agent is used for controlling one or more of cat fleas and American dog ticks.

12. An animal parasite control agent, characterized in that: The animal parasite control agent contains the pyrazole compound according to any one of claims 1 to 4 as an active ingredient, and also contains one or more auxiliary materials; optionally, the amount of the pyrazole compound according to any one of claims 1 to 4 in the animal parasite control agent is 1 to 80% by weight.

13. An animal parasite control composition, characterized in that: A mixture comprising the pyrazole compound according to any one of claims 1 to 4 and other animal parasite control active compounds, wherein the other animal parasite control active compounds are selected from one or more of acaricides, insecticides, parasiticides, and antimalarials.

14. A method for controlling animal parasites, characterized in that: The following steps are involved: An effective dose of material is applied to the animal parasite to be controlled or its growth medium, wherein the material is selected from one or more of the following groups: The pyrazole compound according to any one of claims 1 to 4; The animal parasite control agent according to claim 12; The animal parasite control composition according to claim 13.

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