Pyrazole compound and use thereof

Abstract

Disclosed in the present invention are a pyrazole compound and a use thereof. The structure of the compound is represented by general formula (I). The definition of each substituent in the formula is stated in the description. The description also discloses the use of the compound as an insecticide and acaricide and an animal parasite control agent.

Description

A pyrazole compound and its application Technical Field

[0001] The present 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 No.: Ic-205) and KC2 (Compound No.: Ic-206)

[0003] In the prior art, there are no reports on the compounds represented by the general formula I of the present invention and their insecticidal activity. Moreover, compared with the prior art, the compounds of the present invention have higher insecticidal activity. Summary of the Invention

[0004] The present invention aims to provide a pyrazole compound with better insecticidal and acaricidal activity and its application. The pyrazole compound can be used to prepare drugs for controlling pests and acarids in agriculture and other fields, and in the field of veterinary medicine to prepare drugs for controlling animal parasites.

[0005] In order to achieve the purpose of the present invention, the present invention provides the following technical solutions:

[0006] A pyrazole compound, as shown in the general formula I:

[0007] In the general formula I:

[0008] X is selected from CH or N;

[0009] R1 is selected from H or CN;

[0010] R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or

[0011] R3 is selected from vinyl, C3-C6 cycloalkyl, C1-C4 alkoxy, C1-C3 alkyl or

[0012] 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;

[0013] or a stereoisomer of the compound of formula I;

[0014] or a salt of a compound of formula I;

[0015] or a salt of a stereoisomer of the compound of formula I.

[0016] In one possible implementation, in Formula I,

[0017] X is selected from CH or N;

[0018] R1 is selected from H or CN;

[0019] R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or

[0020] R3 is selected from vinyl, C3-C4 cycloalkyl, C1-C3 alkoxy, C1-C2 alkyl or

[0021] Y1, Y2, Y3, Y4, and Y5 are each independently selected from hydrogen, halogen, cyano, nitro, amino, carboxyl, C1-C4 alkyl, halo-C1-C4 alkyl, C1-C4 alkoxy, halo-C1-C4 alkoxy, C1-C4 alkylthio, or halo-C1-C4 alkylthio;

[0022] or a stereoisomer of the compound of formula I;

[0023] 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;

[0024] 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.

[0025] In one possible implementation, in Formula I,

[0026] X is selected from CH or N;

[0027] R1 is selected from H or CN;

[0028] R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or

[0029] R3 is selected from vinyl, C3-C4 cycloalkyl, C1-C2 alkoxy, C1-C2 alkyl or

[0030] 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;

[0031] or a stereoisomer of the compound of formula I;

[0032] 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;

[0033] 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.

[0034] In one possible implementation, in Formula I,

[0035] X is selected from CH or N;

[0036] R1 is selected from H or CN;

[0037] R2 is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or

[0038] R3 is selected from vinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, CH3OCH2-, CH3CH2OCH2-, CH3CH2CH2OCH2-, (CH3)2CHOCH2-, CH3CH2CH2CH2OCH2-, (CH3)3COCH2-, CH3OCH2CH2-, CH3CH2OCH2CH2-, CH3CH2CH2OCH2CH2-, CH3CH2CH2CH2OCH2CH2- or

[0039] Y1, Y2, Y3, Y4, and 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;

[0040] or a stereoisomer of the compound of formula I;

[0041] 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;

[0042] 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.

[0043] In the definitions of the compounds of the general formula given above, the terms used collectively generally represent the following substituents:

[0044] Halogen: refers to fluorine, chlorine, bromine or iodine.

[0045] Alkyl: straight-chain or branched alkyl, for example methyl, ethyl, n-propyl, isopropyl or the different butyl, pentyl or hexyl isomers.

[0046] Cycloalkyl: refers to a substituted or unsubstituted cyclic alkyl group, such as cyclopropyl, cyclopentyl or cyclohexyl; substituents include methyl, halogen, etc.

[0047] Haloalkyl: a straight-chain or branched alkyl group, in which the hydrogen atoms may be partially or completely replaced by halogen, for example, monochloromethyl, dichloromethyl, trichloromethyl, monobromomethyl, dibromomethyl, tribromomethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, perfluoroethyl, etc.

[0048] Alkoxy: a straight or branched chain alkyl group connected to the structure through an oxygen atom bond, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc.

[0049] Haloalkoxy: The hydrogen atoms on the alkoxy group may be partially or completely replaced by halogen, for example, monochloromethoxy, dichloromethoxy, trichloromethoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, 2,2,2-trifluoroethoxy, etc.

[0050] Alkoxyalkyl: alkyl-O-alkyl-, for example, CH3OCH2-, CH3CH2OCH2-, CH3CH2CH2OCH2-, (CH3)2CHOCH2-, CH3CH2CH2CH2OCH2-, (CH3)3COCH2-, CH3OCH2CH2-, CH3CH2OCH2CH2-, CH3CH2CH2OCH2CH2-, CH3CH2CH2OCH2CH2-, CH3CH2CH2CH2OCH2CH2-, etc.

[0051] Alkylthio: a straight or branched chain alkyl group connected to the structure through a sulfur atom bond, such as methylthio, ethylthio, etc.

[0052] 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.

[0053] Propargyl: CH≡C-CH2-.

[0054] Vinyl group: CH2=CH-.

[0055] Some of the compounds of formula I of the present invention are shown in Tables 1 to 4, but the present invention is by no means limited to these compounds.

[0056] Table 1: In general formula I, when X=N and R1=CN, R2 or R3 are different substituents as shown in Table 1, and the representative compounds are numbered 1.1-1.76.

[0057] Table 1

[0058] Table 2: In general formula I, when X=N and R1=H, the substituent R2 or R3 is consistent with Table 1, and the representative compounds are numbered 2.1-2.76, corresponding to 1.1-1.76 in Table 1.

[0059] Table 3: In general formula I, when X=CH and R1=CN, the substituent R2 or R3 is consistent with Table 1, and the representative compounds are numbered 3.1-3.76, corresponding to 1.1-1.76 in Table 1.

[0060] Table 4: In general formula I, when X=CH and R1=H, the substituent R2 or R3 is consistent with Table 1, and the representative compounds are numbered 4.1-4.76, corresponding to 1.1-1.76 in Table 1.

[0061] The present invention also provides a method for preparing the above-mentioned pyrazole compounds, as follows (unless otherwise specified, the groups in the formula have the same definitions as above, wherein LG = Cl, Br or I):

[0062] 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.

[0063] In one 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.

[0064] The compound of formula VI is reacted with an acyl chloride reagent to prepare a compound of formula V.

[0065] In a possible implementation, the acyl chloride reagent includes one or more of thionyl chloride, oxalyl chloride, phosgene, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride or triphosgene.

[0066] 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.

[0067] 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.

[0068] In one 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.

[0069] In one 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, and sodium tert-butoxide.

[0070] The intermediate compound of formula IX can be prepared by known methods, for example, by referring to the methods reported in WO2021239835 or WO2017055414. The compound of formula II and the compound of formula IV are generally commercially available or can be prepared in-house by conventional methods.

[0071] The embodiments of the present invention also provide use of the above-mentioned pyrazole compounds in the preparation of insecticides and / or acaricides.

[0072] In one possible implementation, the insecticide is used to control one or more of the following insects:

[0073] beetles (Coleopteran), for example, Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum, Epilachna vigintioctomaculata, Agriotes ogurae fuscicollis, Anomala rufocuprea, Leptinotarsa ​​decemlineata, Diabrotica spp., Monochamus alternatus endai, Lissorhoptrus oryzophilus, and Lyctus bruneus;

[0074] Pests of the order of the Lepidopteran, for example, Lymantria dispar (gypsy moth), Malacosoma neustria (yellow tent caterpillar), Pieris rapae crucivora (Japanese cabbage butterfly), Spodoptera litura (spodoptera litura), Mamestra brassicae (cabbage armyworm), Chilo suppressalis (striped stem borer), Ostrinia nubilalis (European corn borer), Cadra cautella (dried fruit borer), Adoxophyes honmai (chyanokokakumonhamaki), Cydiapomonella (apple leaf moth), Agrotis segetum (yellow cutworm), Galleria mellonella (greater wax moth), Plutella xylostella (diamond back moth), Heliothis virescens (tobacco budworm), Phyllocnistis citrella (citrus leafminer);

[0075] Pests of the order Hemipterous, for example, Nephotettix cincticeps, Nilaparvata lugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicas, Aphis pomi, Aphis gossypii, Lipaphis erysimi, Stephanitis nashi, Nezara spp., Trialeurodes vaporariorum, Pshylla spp.;

[0076] Thysanoptera pests, such as Thrips palmi and Franklinella occidentalis;

[0077] Orthopteran pests, such as African mole cricket (Gryllotalpa Africana) and African migratory locust (Locusta migratoria);

[0078] Blattarian pests, for example, German cockroach (Blattella germanica), American cockroach (Periplaneta americana), yellow-breasted termite (Reticulitermes speratus), house termite (Coptotermes formosanus);

[0079] Dipterous pests, such as Musca domestica, Aedes aegypti, Delia platura, Culex pipiens pallens, Anopheles sinensis, Culex tritaeniorhynchus, and Liriomyza trifolii.

[0080] In one 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.

[0081] In a possible implementation, the insecticide and / or acaricide is used to control one or more of armyworms, diamondback moths, and spider mites.

[0082] An embodiment of the present invention further provides an insecticide preparation or acaricide preparation, which contains the above-mentioned pyrazole compound as an active ingredient and one or more auxiliary materials.

[0083] In one possible implementation, the insecticide or acaricide formulation is selected from the following dosage forms: solutions, emulsions, wettable powders, granular wettable powders, suspensions, powders, foams, pastes, tablets, granules, aerosols, natural agents impregnated with active compounds, synthetic agents impregnated with active compounds, microcapsules, seed coatings, formulations equipped with combustion devices (the combustion devices may be chimneys, mist cylinders, canisters, coils, etc.), and ULVs (cold fog, hot fog). These insecticide or acaricide formulations or animal parasite control agents can be prepared using known methods, for example, by mixing the active ingredient with a filler (e.g., a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), and optionally with a surfactant (i.e., an emulsifier and / or a dispersant and / or a foaming agent).

[0084] In a possible implementation, the auxiliary materials include one or more of the following: a filler (e.g., a liquid diluent or carrier, a liquefied gas diluent or carrier, a solid diluent or carrier), a surfactant (e.g., an emulsifier and / or a dispersant and / or a foaming agent), a binder, and a colorant;

[0085] 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 wax (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.), strongly 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;

[0086] Liquefied gas 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;

[0087] Solid diluents may include crushed natural minerals (such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, etc.) and crushed synthetic minerals (such as finely dispersed silicic acid, aluminum oxide and silicates, etc.);

[0088] 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], as well as albumin hydrolyzates, etc.;

[0089] Dispersants may include lignin sulfite waste liquor and methylcellulose;

[0090] Binders may include carboxymethyl cellulose, natural or synthetic polymers (eg, gum arabic, polyvinyl alcohol, polyvinyl acetate, etc.).

[0091] 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.

[0092] Furthermore, the pyrazole compounds of the present invention may be present in a mixture with a synergist, which need not be active itself but rather is a compound which enhances the activity of the active compound.

[0093] 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, or alternatively 0.5 to 90% by weight.

[0094] The present invention also provides an insecticide or acaricide composition comprising a mixture of the above-mentioned pyrazole compound and another active compound (e.g., an insecticide, bait, disinfectant, acaricide, nematicide, fungicide, growth regulator, herbicide, etc.). The mixture can be provided as a bulk drug, or as a commercially available formulation, or in a form derived from the formulation.

[0095] An embodiment of the present invention also provides a method for controlling agricultural or forestry pests and / or mites, comprising 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 compound, the above-mentioned insecticide preparation or acaricide preparation, the above-mentioned insecticide composition or acaricide composition.

[0096] The present invention also provides the use of the pyrazole compounds in preparing an animal parasite control agent. In the veterinary field, i.e., 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.

[0097] In one possible implementation, the animal parasites include one or more of the following:

[0098] 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;

[0099] 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, and Werneckiella equi;

[0100] 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., Tabanus spp. 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 include Aedes aegypti, Aedes albopictus, Aedes taeniorhynchus, Anopheles gambiae, Anopheles maculipennis, Calliphora erythrocephala, Chrysozona pluvialis, Culex five-bandedquinquefasciatus), Culex pipiens, Culex tarsalis, Fannia canicularis, Sarcophaga carnaria, Stomoxys calcitrans, Tipula paludosa, Lucilia cuprina, Lucilia sericata, Simulium reptans, Phlebotomus papatasi, Phlebotomus longipalpis, Odagmia ornata, Wilhelmia equina, Boophthora erythrocephala, Tabanus bromius, Tabanus spodopterus, Tabanus spodopterus, Tabanus sericata, atratus), Tabanus sudeticus, Hybomitra ciurea, Chrysops caecutiens, Chrysops relictus, Haematopota pluvialis, Haematopota italica, Musca autumnalis, Musca domestica, Haematobia irritans irritans, Haematobia irritans exigua, Haematobia stimulans, Hydrotaea irritans, Hydrotaea albipuncta, Chrysomya chloropyga, Chrysomya bezziana, Oestrus ovis, Hypoderma bovis, Hypoderma lineatum), Przhevalskiana silenus, Dermatobia hominis, Melophagus ovinus, Lipoptena capreoli, Lipoptena cervi, Hippobosca variegata, Hippoboscaequina), Gasterophilus intestinalis, Gasterophilus haemorroidalis, Gasterophilus interrnis, Gasterophilus nasalis, Gasterophilus nigricornis, Gasterophilus pecorum, and Braula coeca;

[0101] 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;

[0102] From the order of the Heteropterida, for example, Cimex spp., Triatoma spp., Rhodnius spp., Panstrongylus spp.;

[0103] From the order of the Blattarida, for example, Blatta orientalis, American cockroach, German cockroach, Supella spp. (for example, Suppella longipalpa);

[0104] From the order 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., Pneumonyssus spp.), Pneumonyssus spp., Raillietia spp., Pneumonyssus spp., Sternostoma spp., Varroa spp., Acarapis spp.; in particular, representative examples include 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, Ixodes holocyclus, 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 bursa, Rhipicephalus appendiculatus, Rhipicephalus capensis, Rhipicephalus turanicus, Rhipicephalus zambeziensis, Amblyomma americanum, Amblyomma variegatum, Amblyomma maculatum, Amblyomma ahemebraeum, Amblyomma cajennense, Dermanyssus gallinae, Ornithonyssus bursa, Ornithonyssus sylviarum, and Varroajacobsconi;

[0105] 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.), 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, autumn harvest chigger (Trombicula akamushi), dog ear mite (Otodectes cynotis), cat scab mite (Notoedres cati), dog scabies (Sarcoptes canis), cattle scabies (Sarcoptes bovis), sheep scabies (Sarcoptes ovis), goat scabies (Sarcoptes rupicaprae (=S.caprae), Sarcoptes equi, Sarcoptes suis, Psoroptes ovis, Psoroptes cuniculi, Psoroptes equi, Chorioptes bovis, Psoergates ovis, Pneumonyssoidic mange, Pneumonyssoides caninum, and Acarapis woodi.

[0106] Nematodes, such as the southern root-knot nematode (Meloidogyne incognita), pine wood nematode (Bursaphelenchus xylophilus), rice stem nematode (Aphelenchoides besseyi), soybean nematode (Heterodera glycines), and Pratylenchus spp.;

[0107] Arthropods, helminths, and malarial parasites that attack animals. Controlling arthropods, helminths, and / or malarial parasites reduces mortality in domestic animals and improves animal productivity (meat, milk, wool, hides, eggs, and honey) and health.

[0108] In a possible implementation, the animal parasite control agent is used to control one or more of cat fleas and American dog ticks.

[0109] In one possible implementation, 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.

[0110] An embodiment of the present invention further provides an animal parasite control agent, which contains the above-mentioned pyrazole compound as an active ingredient and one or more auxiliary materials.

[0111] 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, and non-pressure sprays (such as pump sprays and atomized sprays).

[0112] In one possible implementation, the amount of the active ingredient contained in the animal parasite control agent is 1 to 80% by weight.

[0113] The present invention also provides an animal parasite control composition comprising a mixture of the aforementioned pyrazole compound and other active compounds for controlling animal parasites (e.g., acaricides, insecticides, parasiticides, antimalarials, etc.). The mixture can be provided as a bulk drug, or as a commercially available formulation, or in a form derived from the formulation.

[0114] An embodiment of the present invention also provides a method for controlling animal parasites, comprising the following steps: applying an effective dose of a material 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 above-mentioned pyrazole compound; 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, and suppositories; non-enteral administration based on skin application, such as injection (muscular, subcutaneous, intravenous, intraperitoneal, etc.), implantation, nasal administration, including bathing or soaking, spraying, pouring, dripping, washing and dusting, and administration by using molded products containing active compounds, such as collars, ear tags, labels, leg braces, nets, markers, etc. The active compounds of the present invention have low toxicity and can be safely used in warm-blooded animals. Beneficial effects

[0115] The pyrazole compounds of the present invention have unexpectedly excellent insecticidal and acaricidal effects, exhibit suitable control effects against toxic pests, and are non-phytotoxic to cultivated crop plants. Furthermore, the compounds of the present invention can be used to control a variety of pests, such as harmful piercing-sucking insects, chewing insects, other plant parasites, stored grain pests, and sanitary pests, and can be used to disinfect and kill them. DETAILED DESCRIPTION

[0116] The following specific examples are used to further illustrate the present invention, but the present invention is in no way limited to these examples. (Unless otherwise noted, all raw materials used are commercially available)

[0117] Synthesis Example

[0118] According to the synthetic route described above, different raw materials can be used to prepare the compounds represented by the general formula I of the present invention, which are further described in detail as follows:

[0119] Example 1: Preparation of Compound 1.1

[0120] Step 1: Synthesis of intermediate 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile

[0121] To a 100 mL reaction flask, 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. The reaction mixture was brought to reflux and allowed to react for 3 hours. After completion of the reaction, as monitored by TLC, the reaction mixture was concentrated under reduced pressure to dryness and extracted with 50 mL of ethyl acetate and 50 mL of water. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield 1.25 g of an oil, the intermediate 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile.

[0122] Step 2: Synthesis of the intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazolyl]-4-yl)nicotinic acid

[0123] To a 50 mL reaction vial, 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, followed by the addition of tetrakis(triphenylphosphine)palladium (0.16 g, 0.14 mmol), and then degassed under nitrogen for another 10 minutes. The reaction mixture was stirred at 80°C for 6 hours. The reaction mixture was then poured into 30 mL of water and acidified to pH 2 with 2 M HCl. The mixture was extracted twice between ethyl acetate and water. The combined organic layers were dried over magnesium sulfate, filtered, and evaporated to dryness to give a residue. The residue was purified by column chromatography to give 0.93 g of the 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 spectral data of the intermediate are as follows:

[0124] 1 H NMR(600MHz,DMSO-d6)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] - .

[0125] Step 3: Synthesis of intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinoyl chloride

[0126] To a 250 mL reaction flask, add 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinic acid (18.25 g, 37.27 mmol), thionyl chloride (13.30 g, 111.81 mmol), and 100 mL of toluene. Heat to 110°C and react for 3 hours. The reaction solution was concentrated under reduced pressure to obtain 18.63 g of an oil, the intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinic acid chloride.

[0127] Step 4: Synthesis of compound 1.1

[0128] To a 100 mL reaction flask was added 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile (1.25 g, 10.31 mmol), triethylamine (2.09 g, 20.62 mmol), and 50 mL of dichloromethane. With stirring in an ice bath, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinoyl chloride (5.24 g, 10.31 mmol) was added dropwise. After the addition was complete, the reaction mixture was warmed to room temperature and allowed to react for 4 hours. Following completion of the reaction as monitored by TLC, the reaction mixture was concentrated to dryness under reduced pressure and extracted with 150 mL of ethyl acetate and 150 mL of water. The organic phase was washed sequentially with saturated sodium bicarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography to yield 4.93 g of the target compound 1.1 (white solid). The NMR and mass spectrometry data of compound 1.1 are as follows:

[0129] 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] + .

[0130] Example 2: Preparation of Compound 1.3

[0131] Step 1: Synthesis of the intermediate 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinamide

[0132] Referring to the synthesis method of Step 4 of Example 1, 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinamide (white solid) was prepared using 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinamide chloride and 1-amino-1-cyclopropylnitrile hydrochloride as raw materials. The NMR and mass spectrometry data of this intermediate are as follows:

[0133] 1 H NMR(600MHz, Acetonitrile-d3)δ8.74(d,1H),8.32(d,2H),8.12(d,1H),7.67(s,1 H),3.76(s,3H),1.62-1.56(m,2H),1.37-1.32(m,2H).ESI-MS(m / z):553.92[M+H] + .

[0134] Step 2: Synthesis of compound 1.3

[0135] To a 25 mL reaction flask, add 60% NaH (0.03 g, 0.78 mmol) and 10 mL THF. 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'-bipyrazol]-4-yl)nicotinamide (0.29 g, 0.52 mmol) with stirring. Stir at 0-5°C for 30 minutes before adding 4-bromobutyronitrile (0.15 g, 1.01 mmol). Warm the reaction mixture to room temperature and continue stirring for 3 hours. After completion of the reaction, monitor the reaction by TLC and quench with 20 mL of water. Extract the reaction mixture with 50 mL of ethyl acetate and 50 mL of water. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography to yield 0.25 g of a white solid, the target compound 1.3. The NMR and mass spectrometry data of compound 1.3 are as follows:

[0136] 1H NMR (600 MHz, Methanol-d4): 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),2.12(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 / 1H),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] + .

[0137] Example 3: Synthesis of Compound 1.5

[0138] 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'-bipyrazol]-4-yl)nicotinamide and bromoacetonitrile as raw materials. The NMR and mass spectrometry data of Compound 1.5 are as follows:

[0139] 1 H NMR (600 MHz, Methanol-d4): 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] + .

[0140] Example 4: Synthesis of Compound 1.6

[0141] 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'-bipyrazol]-4-yl)nicotinamide and bromomethylcyclopropane as starting materials. The NMR and mass spectrometry data of Compound 1.6 are as follows:

[0142] 1 H NMR (600 MHz, Methanol-d4): The spectrum showed a mixture of rotamers in a ratio of approximately 67:33, δ 8.86 (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]. + .

[0143] Example 5: Synthesis of Compound 1.7

[0144] 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'-bipyrazol]-4-yl)nicotinamide and acryloyl chloride as starting materials. The NMR and mass spectrometry data of Compound 1.7 are as follows:

[0145] 1 H NMR(600MHz,Methanol-d4)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] + .

[0146] Example 6: Synthesis of Compound 1.8

[0147] 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'-bipyrazol]-4-yl)nicotinamide and cyclopropylcarbonyl chloride as starting materials. The NMR and mass spectrometry data of Compound 1.8 are as follows:

[0148] 1 H NMR(600MHz,Methanol-d4)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] + .

[0149] Example 7: Synthesis of Compound 1.13

[0150] 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'-bipyrazol]-4-yl)nicotinamide and ethoxyacetyl chloride as starting materials. The NMR and mass spectrometry data of Compound 1.13 are as follows:

[0151] 1 H NMR (600MHz, Methanol-d4) δ8.83 (dd, 1H), 8.66-8.62 (m, 1H), 8.47 (d, J = 7.9Hz, 1H), 4.18 (s, 1H), 3.8 3(d,3H),3.69(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] + .

[0152] Example 8: Synthesis of Compound 1.21

[0153] 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'-bipyrazol]-4-yl)nicotinamide and benzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 1.21 are as follows:

[0154] 1 H NMR(600MHz,Methanol-d4)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,1H),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] + .

[0155] Example 9: Synthesis of Compound 1.24

[0156] 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'-bipyrazol]-4-yl)nicotinamide and p-fluorobenzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 1.24 are as follows:

[0157] 1 H NMR(600MHz,Methanol-d4)δ8.61(d,1H),8.51(s,1H),8.35(s,1H),8.03(d,1H),7.70-7.66(m,2 H),7.09(t,2H),3.83(s,3H),3.35(s,3H),1.84(s,2H),1.60(s,2H).ESI-MS(m / z):676.08[M+H] + .

[0158] Example 10: Synthesis of Compound 2.1

[0159] Step 1: Synthesis of intermediate 2-(cyclopropyl)aminoacetonitrile

[0160] Referring to the synthetic method of step 1 in Example 1, the intermediate 2-(cyclopropyl)aminoacetonitrile was prepared using cyclopropylamine and bromoacetonitrile as raw materials.

[0161] Step 2: Synthesis of compound 2.1

[0162] 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'-bipyrazol]-4-yl)nicotinoyl chloride as raw materials. The NMR and mass spectrometry data of compound 2.1 are as follows:

[0163] 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] + .

[0164] Example 11: Synthesis of Compound 2.3

[0165] Step 1: Synthesis of the intermediate 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazolyl]-4-yl)nicotinamide

[0166] Referring to the synthesis method of Step 4 of Example 1, the intermediate 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinamide (white solid) was prepared using 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)nicotinamide and cyclopropylamine as raw materials. The NMR and mass spectrometry data of this intermediate are as follows:

[0167] 1 H NMR(600MHz, Acetonitrile-d3)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] + .

[0168] Step 2: Synthesis of compound 2.3

[0169] 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'-bipyrazol]-4-yl)nicotinamide and 4-bromobutyronitrile as raw materials. The NMR and mass spectrometry data of Compound 2.3 are as follows:

[0170] 1 H NMR (600 MHz, Methanol-d4): 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] + .

[0171] Example 12: Synthesis of Compound 2.5

[0172] 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'-bipyrazol]-4-yl)nicotinamide and 3-bromopropyne as starting materials. The NMR and mass spectrometry data of Compound 2.5 are as follows:

[0173] 1H NMR (600 MHz, Methanol-d4): The spectrum showed a mixture of rotamers in a ratio of approximately 90:10, δ 8.80 (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]. + .

[0174] Example 13: Synthesis of Compound 2.7

[0175] 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'-bipyrazol]-4-yl)nicotinamide and acryloyl chloride as starting materials. The NMR and mass spectrometry data of Compound 2.7 are as follows:

[0176] 1 H NMR(600MHz,DMSO-d6)δ8.89(s,1H),8.86(d,1H),8.63(s,1H),8.31(d,1H),7.03(dd,1H),6.29(dd,1H),5.9 5(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] + .

[0177] Example 14: Synthesis of Compound 2.8

[0178] 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'-bipyrazol]-4-yl)nicotinamide and cyclopropylcarbonyl chloride as starting materials. The NMR and mass spectrometry data of Compound 2.8 are as follows:

[0179] 1H NMR(600MHz,Methanol-d4)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] + .

[0180] Example 15: Synthesis of Compound 2.13

[0181] 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'-bipyrazol]-4-yl)nicotinamide and ethoxyacetyl chloride as starting materials. The NMR and mass spectrometry data of Compound 2.13 are as follows:

[0182] 1 H NMR(600MHz,Methanol-d4)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] + .

[0183] Example 16: Synthesis of Compound 2.21

[0184] Referring to the synthesis 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'-bipyrazol]-4-yl)nicotinamide and benzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 2.21 are as follows:

[0185] 1H NMR(600MHz,Methanol-d4)δ8.68(d,1H),8.54(s,1H),8.38(s,1H),8.14(d,1H),7.76(d,2H),7.54(t,1 H),7.46(t,2H),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] + .

[0186] Example 17: Synthesis of Compound 2.24

[0187] 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'-bipyrazol]-4-yl)nicotinamide and p-fluorobenzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 2.24 are as follows:

[0188] 1 H NMR(600MHz,Methanol-d4)δ8.71(d,1H),8.56(s,1H),8.40(s,1H),8.17(d,1H),7.86(dd,2H) ,7.21(t,2H),3.82(s,3H),3.12(tt,1H),0.91(t,2H),0.67(d,2H).ESI-MS(m / z):651.09[M+H] + .

[0189] Example 18: Synthesis of Compound 3.1

[0190] Step 1: Synthesis of the intermediate 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazolyl]-4-yl)benzoic acid

[0191] 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 prepared as raw materials to obtain 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoic acid (yellow solid). The NMR and mass spectrometry data of this intermediate are as follows:

[0192] 1H NMR(600MHz,DMSO-d6)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] - .

[0193] Step 2: Synthesis of 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazolyl]-4-yl)benzoyl chloride

[0194] 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.

[0195] Step 3: Synthesis of compound 3.1

[0196] Referring to the synthesis method of Step 4 of Example 1, Compound 3.1 (white solid) was prepared using 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)benzoyl chloride and 1-((cyanomethyl)amino)cyclopropane-1-carbonitrile as starting materials. The NMR and mass spectrometry data of Compound 3.1 are as follows:

[0197] 1 H 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] + .

[0198] Example 19: Synthesis of Compound 3.2

[0199] Step 1: Synthesis of 2-chloro-N-(1-cyanocyclopropyl)-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)benzamide

[0200] 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.

[0201] The NMR and mass spectrometry data of the intermediate are as follows:

[0202] 1 H NMR(600MHz, Acetonitrile-d3)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] + .

[0203] Step 2: Synthesis of compound 3.2

[0204] 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'-bipyrazol]-4-yl)benzamide and 3-bromopropionitrile as starting materials. The NMR and mass spectrometry data of Compound 3.2 are as follows:

[0205] 1 H NMR (600 MHz, Methanol-d4): The spectrum showed a mixture of rotamers in a ratio of approximately 58:42, δ 8.46 (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]. + .

[0206] Example 20: Synthesis of Compound 3.3

[0207] 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'-bipyrazol]-4-yl)benzamide and 4-bromobutyronitrile as raw materials. The NMR and mass spectrometry data of Compound 3.3 are as follows:

[0208] 1 H NMR (600 MHz, Methanol-d4): 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), 3.9 9(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] + .

[0209] Example 21: Synthesis of Compound 3.5

[0210] 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'-bipyrazol]-4-yl)benzamide and 3-bromopropyne as raw materials. The NMR and mass spectrometry data of compound 3.5 are as follows

[0211] 1H NMR (600 MHz, Methanol-d4): 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),4.73(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,1.95 / 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] + .

[0212] Example 22: Synthesis of Compound 3.6

[0213] 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'-bipyrazol]-4-yl)benzamide and bromomethylcyclopropane as starting materials. The NMR and mass spectrometry data of Compound 3.6 are as follows:

[0214] 1 H NMR (600 MHz, Methanol-d4): 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] + .

[0215] Example 23: Synthesis of Compound 3.7

[0216] 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'-bipyrazol]-4-yl)benzamide and acryloyl chloride as starting materials. The NMR and mass spectrometry data of Compound 3.7 are as follows:

[0217] 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] + .

[0218] Example 24: Synthesis of Compound 3.8

[0219] 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'-bipyrazol]-4-yl)benzamide and cyclopropylcarbonyl chloride as starting materials. The NMR and mass spectrometry data of Compound 3.8 are as follows:

[0220] 1 H NMR(600MHz,Methanol-d4)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] + .

[0221] Example 25: Synthesis of Compound 3.21

[0222] 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'-bipyrazol]-4-yl)benzamide and benzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 3.21 are as follows:

[0223] 1 H NMR(600MHz,Methanol-d4)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] + .

[0224] Example 26: Synthesis of Compound 3.24

[0225] 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'-bipyrazol]-4-yl)benzamide and p-fluorobenzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 3.24 are as follows:

[0226] 1 H NMR(600MHz,Methanol-d4)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] + .

[0227] Example 27: Synthesis of Compound 4.1

[0228] 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'-bipyrazol]-4-yl)benzoyl chloride as starting materials. The NMR and mass spectrometry data of compound 4.1 are as follows:

[0229] 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] + .

[0230] Example 28: Synthesis of Compound 4.2

[0231] Step 1: Synthesis of 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazol]-4-yl)benzamide

[0232] Referring to the synthetic method of step 4 of Example 1, the intermediate 2-chloro-N-cyclopropyl-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzamide was prepared using 2-chloro-5-(2'-methyl-5'-(perfluoroethyl)-4'-(trifluoromethyl)-2'H-[1,3'-bipyrazole]-4-yl)benzoyl chloride and cyclopropylamine as raw materials.

[0233] Step 2: Synthesis of compound 4.2

[0234] Referring to the synthesis 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'-bipyrazol]-4-yl)benzamide and 3-bromopropionitrile as starting materials. The NMR and mass spectrometry data of Compound 4.2 are as follows:

[0235] 1H NMR (600 MHz, Methanol-d4): The spectrum showed a mixture of rotamers in a ratio of approximately 90:10, δ 8.48 (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]. + .

[0236] Example 29: Synthesis of Compound 4.5

[0237] 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'-bipyrazol]-4-yl)benzamide and 3-bromopropyne as starting materials. The NMR and mass spectrometry data of Compound 4.5 are as follows:

[0238] 1 H NMR (600 MHz, Methanol-d4): The spectrum showed a mixture of rotamers in a ratio of approximately 84:16, δ 8.49 (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]. + .

[0239] Example 30: Synthesis of Compound 4.7

[0240] 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'-bipyrazol]-4-yl)benzamide and acryloyl chloride as starting materials. The NMR and mass spectrometry data of Compound 4.7 are as follows:

[0241] 1 H NMR(600MHz,Methanol-d4)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,1H),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] + .

[0242] Example 31: Synthesis of Compound 4.8

[0243] 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'-bipyrazol]-4-yl)benzamide and cyclopropanecarbonyl chloride as starting materials. The NMR and mass spectrometry data of Compound 4.8 are as follows:

[0244] 1 H NMR(600MHz,Methanol-d4)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] + .

[0245] Example 32: Synthesis of Compound 4.21

[0246] Referring to the synthesis 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'-bipyrazol]-4-yl)benzamide and benzoyl chloride as starting materials. The NMR and mass spectrometry data of Compound 4.21 are as follows:

[0247] 1H NMR(600MHz,Methanol-d4)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] + .

[0248] Example 33: Synthesis of Compound 4.24

[0249] Referring to the synthesis method of 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 starting materials. The NMR and mass spectrometry data of Compound 4.24 are as follows:

[0250] 1 H NMR(600MHz,Methanol-d4)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] + .

[0251] Biological activity assay

[0252] Example 34: Bioactivity Assays on Armyworm and Diamondback Moth

[0253] The compounds of the present invention were used to carry out insecticidal activity tests on several insects. The test method is as follows:

[0254] 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 desired concentration.

[0255] The activity was determined using the Airbrush spray method with armyworm and diamondback moth as targets.

[0256] (1) Determination of activity against armyworms

[0257] Test method: Cut corn leaves into 2 cm long segments and spray them with Airbrush at a pressure of 10 psi (about 0.7 kg / cm 2 ) Spray each leaf segment on both sides with a spray volume of 0.5 mL of the test compound. After drying in the shade, inoculate 10 third-instar larvae per treatment, with three replicates per treatment. After treatment, incubate in an observation room at 25°C and a relative humidity of 60-70%. Three days after treatment, count the number of surviving larvae and calculate mortality.

[0258] Some of the results of the tests on armyworms are as follows:

[0259] At a dose of 0.625 mg / L, three 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%.

[0260] (2) Determination of activity against diamondback moth

[0261] Test method: Use a punch to punch the cabbage leaves into 2cm diameter leaf discs and spray them with an Airbrush at a pressure of 10psi (about 0.7kg / cm 2 ) Spray both sides of each leaf disc with 0.5 mL of the test compound. After drying in the shade, inoculate 10 third-instar larvae per treatment, with three replicates per treatment. After treatment, incubate in an observation room at 25°C and a relative humidity of 60-70%. Three days after treatment, count the number of surviving larvae and calculate mortality.

[0262] Some of the test results on diamondback moth are as follows:

[0263] At a dose of 0.625 mg / L, three 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 the diamondback moth were all above 90%.

[0264] Some compounds of the present invention and control compounds were selected for parallel comparative test of insecticidal activity against diamondback moth (3 days after application), and the determination method was the same as described above; the results are shown in Table 5:

[0265] Table 5 Parallel comparison test of insecticidal activity of some compounds of the present invention and control compounds against Plutella xylostella

[0266] 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 were obtained by following the methods of the present invention. All starting materials can be prepared according to the methods of the present invention, are commercially available, or can be prepared by conventional methods.

[0267] 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] + .

[0268] 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] + .

[0269] KC3: white solid. 1H NMR(600MHz,Methanol-d4)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] + .

[0270] KC4: white solid. 1 H NMR(600MHz,Methanol-d4)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] + .

[0271] In the examples of the present invention, compounds with better insecticidal effects were obtained by selecting X, R1, R2, R3, Y1, Y2, Y3, Y4, Y5 and their combinations in the compounds of formula I. As shown in Table 5, by comparing compounds 3.1, 3.5, and 3.6 with the control compound KC2, by comparing compounds 3.7 and 3.8 with the control compound KC1, and by comparing compounds 1.7, 1.8, and 1.13 with the control compounds KC3 and KC4, it can be seen that: since R2 in the compounds of formula I of the present invention is selected from CNCH2-, CNCH2CH2-, CNCH2CH2CH2-, CNCH2CH2CH2CH2-, propargyl, cyclopropylmethyl or and R3 is selected from vinyl, C3-C6 cycloalkyl, C1-C4 alkoxy, C1-C3 alkyl or And 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, so that the compounds of the present invention have unexpectedly high insecticidal activity.

[0272] Example 35: Biological Activity Assay of Tetranychus cinnabarinus

[0273] The greenhouse mite killing activity of the compound of the present invention was determined as follows:

[0274] According to the solubility of the test compound, dissolve it in acetone or dimethyl sulfoxide, and prepare 50 mL of the test solution of the required concentration with 0.1% Tween 80 solution. The content of acetone or dimethyl sulfoxide in the solution shall not exceed 10%.

[0275] Take two true leaf bean seedlings and inoculate them with 30-40 adult spider mites. After investigating the base number, use a handheld sprayer to spray the entire plant. Repeat each treatment 3 times. After treatment, place the seedlings in a standard observation room. After 72 hours, investigate the number of surviving mites and calculate the mortality rate.

[0276] Some test results on adult Tetranychus cinnabarinus are as follows:

[0277] At a dose 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 Tetranychus cinnabarinus were all above 90%.

[0278] Example 36: Insecticidal test on cat fleas

[0279] 4 mg of the test compound was dissolved in 40 mL of acetone to obtain a 100 mg / L acetone solution. 400 μL of the solution was applied to the bottom and sides of a 5.3 cm inner diameter culture dish. 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 Ten adult cat fleas (mixed males and females) were placed in the container, covered, and stored in a constant temperature chamber at 25°C. The number of dead fleas after 72 hours was counted, and the mortality rate was calculated. The test was repeated three 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, and 4.24 showed a mortality rate of over 70%.

[0280] Example 37: Insecticidal test on American dog tick

[0281] 4 mg of the test compound was dissolved in 40 mL of acetone to obtain a 100 mg / L acetone solution. 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 . Ten 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 miticide is used for preventing and controlling one or more of armyworm, diamondback moth, 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 amount 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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