A preparation method of a C-fluoroalkyl substituted amidine compound and its application in combating fungal diseases

Abstract

This disclosure relates to a method for preparing a compound represented by formula (I), comprising reacting a compound represented by formula (II) with compounds represented by formula (III) and formula (IV) under the catalytic presence of a catalyst and the presence of a fluoride salt to obtain the compound represented by formula (I). The compound represented by formula (I) prepared by this method exhibits antifungal activity and can be used as a fungicide. Its pesticide composition can be used to control plant diseases. The compound can effectively prevent pathogens from infecting plants by inhibiting conidial germination, germ tube growth, or appressorium formation. It can be used to control devastating plant diseases, including rice blast, anthracnose, downy mildew, phytophthora, and powdery mildew, providing a new option for plant protection. #imgabs0#

Description

Technical Field

[0001] The present invention belongs to the field of medicines or pesticides, and particularly relates to a preparation method of a C-fluoroalkyl substituted amidine compound and its application in resisting fungal diseases. Background Art

[0002] 70-80% of plant diseases are caused by fungi and oomycetes. Several, even dozens, of different fungal and oomycete diseases can occur on a single plant. For example, rice diseases such as sheath blight, blast, false smut, sesame spot, and seedling blight; wheat diseases such as head blight, powdery mildew, stripe rust, stem rust, leaf rust, root rot, and sheath blight; and corn diseases such as large leaf spot, small leaf spot, stem base rot, rust, sheath blight, Curvularia leaf spot, head smut, and powdery mildew are all caused by fungi. These fungal diseases account for over 90% of the total area affected and the losses caused by crop diseases. In addition to fungal diseases, oomycete diseases, such as potato late blight, soybean phytophthora, pepper phytophthora, grape downy mildew, and cucumber downy mildew, are also serious threats to many crops.

[0003] For plant diseases caused by fungi and oomycetes, chemical agents are generally used as the primary control method. Commonly used fungicides for chemical control include boscalid, cyproconazole, thiophanate-methyl, carbendazim, azoxystrobin, pyraclostrobin, prochloraz, and tricyclazole. Among them, thiophanate-methyl, azoxystrobin, prochloraz, and tricyclazole are used as protectants, while thiophanate-methyl, thiophanate-methyl, carbendazim, and pyraclostrobin act as both protectants and cures.

[0004] Most diseases caused by fungi and oomycetes are primarily transmitted in the field via asexual spores. Many asexual spores of these fungi, such as Pyricularia oryzae and Colletotrichum, germinate after attaching to plant surfaces. These conidia expand at the apex of the germ tube to form a melanized appressorium. Under the influence of the immense turgor pressure within the appressorium, these conidia differentiate from the base of the appressorium to form an infection spike, which then invades plant tissues and causes disease. Appressoriums are specialized infection structures formed by many plant and animal pathogens. Therefore, a deeper understanding of the molecular mechanisms of appressorium formation and maturation could provide candidate targets for the development of green fungicides. However, there are currently few fungicides on the market that specifically inhibit appressorium formation and maturation. Tricyclazole is the only pesticide that specifically inhibits appressorium maturation to prevent disease. Tricyclazole's mechanism of action is to inhibit the enzymes trihydroxynaphthol reductase and tetrahydroxynaphthol reductase, which are involved in the biosynthesis of melanin in the appressorium. This, in turn, inhibits appressorium maturation, preventing the appressorium from generating the immense turgor pressure and, consequently, losing its ability to invade host plant cells. Therefore, developing inhibitors against key pathogenic proteins that control appressorium formation and maturation in pathogens can provide a new approach for the development of new fungicides for plant fungal and oomycete diseases.

[0005] Amidine compounds are a very important class of nitrogen-containing compounds, widely used in pharmaceuticals and pesticides for analgesia, antipyretics, antibacterial and anti-inflammatory effects, and insecticides. Examples include the first-generation cephalosporin antibiotic cefathiamidine, the sedative and hypnotic drug methaqualone, and the commonly used insecticide acetamiprid. However, amidine compounds have also been reported to be effective in controlling fungal and oomycete diseases in crops (e.g., propamidine). The introduction of fluorine atoms and fluorine-containing substituents often alters the physicochemical properties of the drug nucleus, such as lipid solubility and metabolic stability, and can alter the molecule's biological activity, cell membrane permeability, and bioavailability. Consequently, fluorinated molecules have consistently occupied a high proportion of pharmaceutical and pesticide research and development in recent years. Examples include Lipitor, a drug for the treatment of hypercholesterolemia and mixed hyperlipidemia, sofosbuvir, a drug for hepatitis C, and cyhalothrin, an insecticide and acaricide.

[0006] However, the existing technology for the synthesis of such amidine structures has the following disadvantages: (1) the substrate needs to be pre-functionalized, such as imine chloride, amide, etc. need to be prepared in advance; (2) the reaction conditions are harsh, requiring the use of strong bases, toxic reagents (such as carbon tetrachloride, iodine, etc.), heating conditions, etc.; (3) the universality of the reaction substrates is limited, such as the nucleophilic reaction of difluoroimines with amine compounds is only used to synthesize difluoromethyl-substituted amidines; (4) the atom economy is poor, such as the coupling reaction of 2-aminobenzamide with trifluoromethylimidoyl chloride will leave the larger imine group. Summary of the Invention

[0007] To improve the above technical problems, the present invention provides a method for preparing a compound represented by formula (I), comprising the following steps: reacting a compound represented by formula (II), a compound represented by formula (III), and a compound represented by formula (IV) in the presence of a catalyst and a fluoride salt to obtain a compound represented by formula (I);

[0008]

[0009] in,

[0010] R 1 is selected from unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 3-20 Cycloalkyl, -C(O)-R 5 、-C(O)-OR 5 、-S(O)2-R 6 、-S(O)2-OR 6 OR-P(O)(OR 7 )(OR 8 );

[0011] R 2is selected from unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclic group, C 3-20 Cycloalkyl, C 1-20 alkyl;

[0012] R Si Selected from alkyl silicon reagents, such as R Si1 、R Si2 、R Si3 The same or different, independently selected from C 1-6 alkyl;

[0013] R F Selected from fluorinated C 1-20 alkyl;

[0014] R 5 、R 6 、R 7 、R 8 The same or different, independently selected from unsubstituted or optionally substituted by one, two or more R c Substituted with the following groups: C 1-20 Alkyl, C 3-20 Cycloalkyl, C 2-20 Alkenyl, C 2-20 Alkynyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl;

[0015] Each R a 、R b 、R c The same or different, independently selected from H, oxo, halogen, nitro, unsubstituted or optionally substituted by one, two or more R d Substituted with the following groups: C 1-20 Alkyl, C 1-20 Alkyloxy, halogenated C 1-20 Alkyl, halogenated C 1-20 Alkyloxy, C 2-20 Alkenyl, C 2-20 Alkynyl, C 3-20 Cycloalkyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C(O)OR 9 、-C(O)-R 9 、-C(O)-NH-R 9 、-NR 9 R 10 、-S(O)2-R 9 、-S(O)2-OR 9 ;

[0016] R 9 、R 10 The same or different, independently selected from H, C 1-20 Alkyl, C 3-20 Cycloalkyl, C 6-20 Aryl, 5-20 membered heteroaryl, 3-20 membered heterocyclyl;

[0017] Each R d The same or different, independently selected from H, oxo, halogen, nitro, C 1-20 Alkyl, C 1-20 Alkyloxy, halogenated C 1-20 Alkyl, halogenated C 1-20 Alkyloxy, C 3-20 Cycloalkyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, -C(O)OC 1-20 Alkyl, -C(O)C 1-20 alkyl.

[0018] According to an embodiment of the present invention, R 1 is selected from unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: C 6-10 Aryl, 5-10 membered heteroaryl, -C(O)-R 5 、-S(O)2-R 6 OR-P(O)(OR 7 )(OR 8 );

[0019] According to an embodiment of the present invention, R 1 is selected from unsubstituted or optionally substituted with one, two or more R a Substituted: phenylsulfonyl, naphthylsulfonyl, benzoyl, phenyl, naphthyl, thienylsulfonyl, benzothienyl, -P(O)(OCH3)(OCH3), -P(O)(OPh)(OPh), methylsulfonate;

[0020] According to an embodiment of the present invention, R 5 、R 6 、R 7 、R 8 The same or different, independently selected from unsubstituted or optionally substituted by one, two or more R c Substituted with the following groups: C 1-6 Alkyl, C 6-10 Aryl, 5-10 membered heteroaryl;

[0021] According to an embodiment of the present invention, R 5 、R 6 、R7 、R 8 The same or different, independently selected from unsubstituted or optionally substituted by one, two or more R c Substituted groups: methyl, phenyl, naphthyl, thienyl.

[0022] According to an embodiment of the present invention, each R a 、R b 、R c The same or different, independently selected from H, F, Cl, Br, nitro, unsubstituted or optionally substituted by one, two or more R d Substituted with the following groups: C 1-6 Alkyl, C 1-6 Alkyloxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkyloxy, C 6-10 Aryl, 5-10 membered heteroaryl, C(O)OC 1-6 alkyl;

[0023] According to an embodiment of the present invention, each R a 、R b 、R c The same or different, independently selected from H, F, Cl, Br, methyl, methoxy, trifluoromethyl, nitro, phenyl, pyrazolyl.

[0024] According to an embodiment of the present invention, each R d The same or different, independently selected from halogenated C 1-6 Alkyl, C 6-10 Aryl; for example, trifluoromethyl, phenyl.

[0025] According to an embodiment of the present invention, R 1 selected from phenylsulfonyl, 4-tolylsulfonyl, 4-methoxyphenylsulfonyl, 4-trifluoromethylphenylsulfonyl, 3-nitrophenylsulfonyl, 4-bromophenylsulfonyl, 4-fluorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-naphthylsulfonyl, 4-tolylcarbonyl, 3-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 4-(ethylformyl)phenyl, 3-alkynylphenyl, 1-naphthyl, pentafluorophenyl, 2,5-xylyl, 2-thiophenesulfonyl Di(4-methylphenyl) phosphate diphenyl phosphate dimethyl phosphate 3-Benzothiphenyl 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonyl 2,3:4,5-Bis-O-(1-methylethylidene)-β-D-fructopyranosesulfonyl

[0026] According to an embodiment of the present invention, R 2 Selected from C 1-6 Alkyl, C 1-6 Alkyl C 6-10 aryl;

[0027] According to an embodiment of the present invention, R 2 Selected from tert-butyl, 2,5-xylyl, and 2-tert-butylphenyl.

[0028] According to an embodiment of the present invention, R Si Selected from trimethylsilyl, triethylsilyl, methyldiethylsilyl, triisopropylsilyl, tert-butyldimethylsilyl.

[0029] According to an embodiment of the present invention, R F Selected from fluorinated C 1-6 Alkyl; for example, selected from trifluoromethyl, difluoromethyl, pentafluoroethyl.

[0030] According to an embodiment of the present invention, the compound of formula (II) is selected from phenylmethanesulfonyl azide, 4-methylphenylmethanesulfonyl azide, 4-methoxyphenylmethanesulfonyl azide, 4-trifluoromethylphenylmethanesulfonyl azide, 3-nitrobenzenemethylsulfonyl azide, 4-bromophenylmethanesulfonyl azide, 4-fluorophenylmethanesulfonyl azide, 4-chlorophenylmethanesulfonyl azide, 2-naphthalenesulfonyl azide, 2-thiophenesulfonyl azide, di-p-tolylphosphoryl azide, diphenylphosphoryl azide, dimethylphosphoryl azide, p-toluoyl benzoyl azide, 3-nitrophenylmethane ... 4-Fluorophenyl azide, 4-chlorophenyl azide, 4-bromophenyl azide, 4-methoxyphenyl azide, 4-trifluoromethoxy azide, 4-ethylformate phenyl azide, 3-alkynylphenyl azide, 1-naphthyl azide, pentafluorophenyl azide, 3-benzothiophene azide, 2,6-dimethylphenyl azide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonyl azide, 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose azidesulfonate.

[0031] According to an embodiment of the present invention, the compound of formula (III) is selected from tert-butyl isocyanide, 2,6-dimethylphenyl isocyanide, 2-tert-butylphenyl isocyanide.

[0032] According to an embodiment of the present invention, the compound of formula (IV) is selected from trifluoromethyltrimethylsilane, pentafluoroethyltrimethylsilane, difluoromethyltrimethylsilane.

[0033] According to an embodiment of the present invention, the catalyst can be a metal catalyst, such as a palladium catalyst, a rhodium catalyst, or a nickel catalyst; the catalyst can be a metal, a metal salt, or a complex composed of a metal and a phosphine-containing ligand, a nitrogen-containing ligand, an oxygen-containing ligand, a sulfur-containing ligand, or an alkenyl ligand; the palladium catalyst is, for example, selected from at least one of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), bis(triphenylphosphine)palladium chloride (Pd(PPh3)2Cl2), sodium tetrachloropalladate (Na2PdCl4), palladium carbon (Pd / C), and palladium hydroxide (Pd(OH)2), preferably Pd2(dba)3. The rhodium catalyst can be selected from rhodium carbon (Rh / C), acetylacetonato (1,5-cyclooctadiene) rhodium (Rh(cod)acac), dipolymerized hydroxy(1,5-cyclooctadiene) rhodium ({Rh(cod)OH}2), and dipolymerized (1,5-cyclooctadiene) rhodium chloride ({Rh(Cod)Cl}2); the nickel catalyst can be selected from bis(tricyclohexylphosphine) nickel dichloride ([(Cy)3P]2NiCl2), bis(triphenylphosphine) nickel chloride ((Ph3P)2NiCl2), and bis-(1,5-cyclooctadiene) nickel (Ni(cod)2).

[0034] According to an embodiment of the present invention, the fluoride salt is selected from alkali metal or alkaline earth metal salts of fluoride, for example, at least one selected from potassium fluoride, calcium fluoride, sodium fluoride, tetrabutylammonium fluoride, tetramethylammonium fluoride, and silver fluoride; preferably, cesium fluoride.

[0035] According to an embodiment of the present invention, the molar ratio of the compound of formula (II), the compound of formula (III), and the compound of formula (IV) can be (0.5-3):1:(0.8-5), for example (1.1-1.5):1:(1.5-3), such as 1:1:1, 1:1:2, 1:1:3, 1:1:5, 0.8:1:3, 1.1:1:3, 1.2:1:3, and 1.5:1:3.

[0036] According to an embodiment of the present invention, the molar ratio of the palladium catalyst to the compound of formula (II) is 0.001-5%, for example 0.05-5%, such as 0.1%, 0.2%, 0.5%, 1%, 2%, 3%.

[0037] According to an embodiment of the present invention, the molar ratio of the fluoride salt to the compound of formula (II) is (0.5-3):1, for example (0.8-2):1, such as 1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.8:1.

[0038] According to an embodiment of the present invention, the reaction can be carried out in the presence of a solvent, and the solvent is, for example, at least one selected from tetrahydrofuran, 1,4-dioxane, 2-methyltetrahydrofuran, dichloromethane, 1,2-dichloroethane, chloroform, diethyl ether, methyl n-butyl ether, methanol, ethanol, isopropanol, benzene, toluene, acetonitrile, nitromethane, pentane, and hexane.

[0039] According to an embodiment of the present invention, the reaction may be carried out in the presence of an inert atmosphere, preferably nitrogen.

[0040] According to an embodiment of the present invention, the reaction temperature of the reaction is, for example, selected from -10°C to 50°C, preferably 20°C to 30°C.

[0041] According to an embodiment of the present invention, the reaction time of the reaction is, for example, selected from 2 to 24 hours, preferably 4 to 18 hours.

[0042] According to an embodiment of the present invention, the method further comprises a concentration step. Preferably, the concentration process can be carried out by atmospheric distillation, reduced pressure distillation or the like.

[0043] According to an embodiment of the present invention, the method further comprises a purification step. Preferably, the purification step is performed by column chromatography, vacuum distillation and / or recrystallization to obtain a pure product. More preferably, the purification step is performed by column chromatography followed by vacuum distillation to obtain the purified product.

[0044] The present invention also provides a compound represented by formula (I), its stereoisomers, tautomers, racemates or pesticide-acceptable salts thereof:

[0045]

[0046] Among them, R 1 、R 2 、R F Has the definition as above.

[0047] According to an embodiment of the present invention, R 1 is selected from unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: C 6-10 Aryl, 5-10 membered heteroaryl, -C(O)-R 5 、-C(O)-OR 5 、-S(O)2-R 6 、-S(O)2-OR 6 OR-P(O)(OR 7 )(OR 8 );

[0048] According to an embodiment of the present invention, R1 is selected from unsubstituted or optionally substituted with one, two or more R a Substituted: phenylsulfonyl, naphthylsulfonyl, benzoyl, phenyl, naphthyl, thienylsulfonyl, benzothienyl, -P(O)(OCH3)(OCH3), -P(O)(OPh)(OPh), methylsulfonate;

[0049] According to an embodiment of the present invention, R 5 、R 6 、R 7 、R 8 The same or different, independently selected from unsubstituted or optionally substituted by one, two or more R c Substituted with the following groups: C 1-6 Alkyl, C 6-10 Aryl, 5-10 membered heteroaryl;

[0050] According to an embodiment of the present invention, R 5 、R 6 、R 7 、R 8 The same or different, independently selected from unsubstituted or optionally substituted by one, two or more R c Substituted groups: methyl, phenyl, naphthyl, thienyl.

[0051] According to an embodiment of the present invention, each R a 、R b 、R c The same or different, independently selected from H, F, Cl, Br, unsubstituted or optionally substituted by one, two or more R d Substituted with the following groups: C 1-6 Alkyl, C 1-6 Alkyloxy, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkyloxy, C 6-10 Aryl, 5-10 membered heteroaryl, C(O)OC 1-6 alkyl;

[0052] According to an embodiment of the present invention, each R a 、R b 、R c The same or different, independently selected from H, F, Cl, Br, methyl, methoxy, trifluoromethyl, nitro, phenyl, pyrazolyl.

[0053] According to an embodiment of the present invention, each R d The same or different, independently selected from halogenated C 1-6 Alkyl, C 6-10 Aryl; for example, trifluoromethyl, phenyl.

[0054] According to an embodiment of the present invention, R 1 is selected from the group consisting of phenylsulfonyl, 4-tolylsulfonyl, 4-methoxyphenylsulfonyl, 4-trifluoromethylphenylsulfonyl, 3-nitrophenylsulfonyl, 4-bromophenylsulfonyl, 4-fluorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-naphthylsulfonyl, 4-tolylcarbonyl, 3-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 4-(ethylformyl)phenyl, 3-alkynylphenyl, 1-naphthyl, pentafluorophenyl, 2,5-xylyl,

[0055] According to an embodiment of the present invention, the compound represented by formula (I) is selected from the following compounds:

[0056]

[0057]

[0058]

[0059]

[0060]

[0061] The present invention also provides a compound represented by formula (I), its stereoisomers, tautomers, racemates or pesticide-acceptable salts, and their use in preparing drugs for preventing or controlling crop diseases, such as their use in preparing fungicides.

[0062] According to an embodiment of the present invention, the disease can be a crop disease caused by fungi or oomycetes, such as rice sheath blight, rice blast, rice false smut, sesame spot and seedling blight, etc., wheat fusarium rust, powdery mildew, stripe rust, stem rust, leaf rust, root rot and sheath blight, etc., corn large leaf spot, small leaf spot, stem base rot, rust, sheath blight, Curvularia leaf spot, head smut, powdery mildew, potato late blight, soybean phytophthora, pepper phytophthora, grape downy mildew and cucumber downy mildew.

[0063] The present invention also provides a fungicide composition, comprising a compound represented by formula (I), its stereoisomers, tautomers, racemates or pesticide-acceptable salts.

[0064] According to an embodiment of the present invention, the fungicidal composition further comprises a pesticide-acceptable carrier. Preferably, the pesticide-acceptable carrier can be selected from at least one of an inert material, a surfactant, a solvent and other additives.

[0065] The present invention also provides a method for sterilizing crops, comprising applying a compound represented by formula (I), its stereoisomers, tautomers, racemates or pesticide-acceptable salts or the sterilizing composition in a sterilizing active amount to crops, crop seeds and / or their growth environment.

[0066] Beneficial effects

[0067] The present invention provides a method for preparing a C-fluoroalkyl substituted amidine compound represented by formula (I), and the compound and its application in resisting fungal diseases. The compound has good fungicidal effect on crops and can be used to prepare pesticides.

[0068] The present method for preparing the compound represented by formula (I) utilizes a simple azide compound (compound (II)), an isonitrile compound (compound (III)), and a silicon-based fluorine reagent (compound (IV)) as raw materials, utilizes a metal-containing catalyst, and undergoes a catalytic process under certain reaction conditions to obtain a fluoroalkyl-substituted amidine compound in relatively high yield. The method has good substrate universality. Compared with existing methods, the present invention has the following advantages:

[0069] 1. The three-component cascade reaction process involved in the present invention is relatively simple and no other special additives, such as oxidants, strong bases, etc., are required.

[0070] 2. The reaction raw materials involved in the present invention are simple and easy to obtain. The reaction uses azide, isonitrile and silicon-based fluorine reagent as substrates. Compared with other complex substrates, the reaction can obtain the corresponding amidine compounds in one go.

[0071] 3. The reactions involved in the preparation method of the present invention have good tolerance and universality for functional groups. The azide can be an aryl, heteroaryl, alkyl, sulfonyl, phosphonyl, etc., the isonitrile can be an aryl, alkyl, etc., and the silyl fluorine reagent can be a trifluoromethyl, difluoromethyl, pentafluoroethyl reagent, etc. The method of the present invention can prepare amidine compounds containing N-sulfonyl, phosphonyl, acyl, aryl, trifluoromethyl, difluoromethyl, pentafluoroethyl, etc. substitutions.

[0072] Definitions and Explanations of Terms

[0073] Unless otherwise indicated, the definitions of groups and terms in this specification and claims, including definitions used as examples, exemplary definitions, preferred definitions, definitions in tables, and definitions of specific compounds in the Examples, may be arbitrarily combined and coupled with one another. The group definitions and compound structures resulting from such combinations and couplings should be understood to be within the scope of this specification and / or claims.

[0074] The term "C 1-20"Alkyl" is understood to mean a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 20 carbon atoms. For example, "C 1-10 "Alkyl" means straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, "C 1-8 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, or 8 carbon atoms, "C 1-6 The term "alkyl" refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5 or 6 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, or the like or isomers thereof.

[0075] The term "C 2-20 "Alkenyl" is understood to mean a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2 to 20 carbon atoms, preferably "C 2-10 Alkenyl". "C 2-10 "Alkenyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, more preferably "C 2-8 Alkenyl". "C 2-10 "Alkenyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2, 3, 4, 5, 6, 7 or 8 carbon atoms, e.g. 2-6 alkenyl), having 2 or 3 carbon atoms (i.e., C 2-3It is understood that when the alkenyl group contains more than one double bond, the double bonds may be separated from one another or conjugated. The alkenyl group is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)- Pent-1-enyl, (Z)-pent-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-methylprop-2-enyl, 1-methylprop-2-enyl , 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl, (Z)-1-methyl But-2-enyl, (E)-3-methylbut-1-enyl, (Z)-3-methylbut-1-enyl, (E)-2-methylbut-1-enyl, (Z)-2-methylbut-1-enyl, (E)-1-methylbut-1-enyl, (Z)-1-methylbut-1-enyl, 1,1-dimethylprop-2-enyl, 1-ethylprop-1-enyl, 1-propylvinyl, 1-isopropylvinyl.

[0076] The term "C 2-20 "Alkynyl" is understood to mean a linear or branched monovalent hydrocarbon radical containing one or more triple bonds and having 2 to 20 carbon atoms, preferably "C 2-10 Alkynyl". The term "C 2-10 "Alkynyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical containing one or more triple bonds and having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, e.g. having 2, 3, 4, 5, 6, 7 or 8 carbon atoms (i.e. "C 2-8 alkynyl”), having 2, 3, 4, 5, or 6 carbon atoms (i.e., “C 2-6 Alkynyl”), having 2 or 3 carbon atoms (“C 2-3The alkynyl group is, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, In some embodiments, the alkynyl group is ethynyl, prop-1-ynyl or prop-2-ynyl.

[0077] The term "C 3-20 "Cycloalkyl" is understood to mean a saturated monovalent monocyclic, bicyclic (such as condensed, bridged, spiro) hydrocarbon ring or tricyclic alkane having 3 to 20 carbon atoms, preferably "C 3-10 Cycloalkyl", more preferably "C 3-8 Cycloalkyl". The term "C 3-10 "Cycloalkyl" is understood to mean a saturated monovalent monocyclic, bicyclic (eg bridged, spiro) hydrocarbon ring or tricyclic alkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. 3-10 The cycloalkyl group may be a monocyclic hydrocarbon group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, or a bicyclic hydrocarbon group such as borneol, indolyl, hexahydroindolyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 2,7-diazaspiro[3,5]nonyl, 2,6-diazaspiro[3,4]octyl, or a tricyclic hydrocarbon group such as adamantyl.

[0078] The term "3-20 membered heterocyclyl" refers to a saturated or unsaturated non-aromatic ring or ring system, for example, a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic ring (such as a fused ring, a bridged ring, a spirocyclic ring) or a 10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system, and contains at least one, for example 1, 2, 3, 4, 5 or more heteroatoms selected from O, S and N, wherein N and S may also be optionally oxidized to various oxidation states to form nitrogen oxides, -S(O)- or -S(O)2- states. Preferably, the heterocyclyl may be selected from "3-10 membered heterocyclyl". The term "3-10 membered heterocyclyl" means a saturated or unsaturated non-aromatic ring or ring system, and contains at least one heteroatom selected from O, S and N. The heterocyclic group can be connected to the rest of the molecule by any one of the carbon atoms or nitrogen atom (if present). The heterocyclic group can include fused or bridged rings and spirocyclic rings. In particular, the heterocyclic group can include but is not limited to: 4-membered rings, such as azetidinyl, oxetane; 5-membered rings, such as tetrahydrofuranyl, dioxolyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl; or 6-membered rings, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl; or 7-membered rings, such as diazepanyl. Optionally, the heterocyclic group can be benzo-fused. The heterocyclic group may be bicyclic, such as, but not limited to, a 5,5-membered ring, such as a hexahydrocyclopenta[c]pyrrol-2(1H)-yl ring, or a 5,6-membered bicyclic ring, such as a hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl ring. The heterocyclic group may be partially unsaturated, i.e., it may contain one or more double bonds, such as, but not limited to, dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrrolyl, 4H-[1,3,4]thiadiazinyl, 1,2,3,5-tetrahydrooxazolyl, or 4H-[1,4]thiazinyl, or it may be benzo-fused, such as, but not limited to, dihydroisoquinolinyl. When the 3-20-membered heterocyclic group is linked to other groups to form the compounds of the present invention, the linking may be to a carbon atom of the 3-20-membered heterocyclic group or to a heterocyclic atom on the 3-20-membered heterocyclic group ring. For example, when the 3-20 membered heterocyclic group is selected from piperazinyl, the nitrogen atom on the piperazinyl group may be connected to the other group. Or when the 3-20 membered heterocyclic group is selected from piperidinyl, the nitrogen atom on the piperidinyl ring and the carbon atom at the para position thereof may be connected to the other group.

[0079] The term "C 6-20 "Aryl" should be understood to preferably mean a monovalent aromatic or partially aromatic monocyclic, bicyclic (such as fused, bridged, spiro) or tricyclic hydrocarbon ring having 6 to 20 carbon atoms, which can be a single aromatic ring or a polyaromatic ring fused together, preferably "C 6-14Aryl". The term "C 6-14 "Aryl" is understood to mean preferably a monovalent aromatic or partially aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring ("C 6-14 or a ring having 9 carbon atoms ("C9 aryl"), for example indanyl or indenyl, or a ring having 10 carbon atoms ("C 10 aryl) such as tetrahydronaphthyl, dihydronaphthyl or naphthyl, or a ring having 13 carbon atoms ("C 13 aryl), such as fluorenyl, or a ring having 14 carbon atoms ("C 14 aryl”), such as anthracenyl. When the C 6-20 When the aryl group is substituted, it may be monosubstituted or polysubstituted. Furthermore, there is no limitation on the position of substitution, and for example, substitution may be at the ortho, para or meta position.

[0080] The term "5-20 membered heteroaryl" is understood to include monovalent monocyclic, bicyclic (e.g. fused, bridged, spiro) or tricyclic aromatic ring systems having 5 to 20 ring atoms and containing 1 to 5 heteroatoms independently selected from N, O and S, for example "5-14 membered heteroaryl". The term "5-14 membered heteroaryl" is understood to include monovalent monocyclic, bicyclic or tricyclic aromatic ring systems having 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 ring atoms, in particular 5 or 6 or 9 or 10 carbon atoms, and containing 1 to 5, preferably 1 to 3, heteroatoms each independently selected from N, O and S and, in each case, may be benzo-fused. "Heteroaryl" also refers to a radical in which a heteroaromatic ring is fused to one or more aryl, alicyclic or heterocyclyl rings, wherein the radical or point of attachment is on the heteroaromatic ring. Non-limiting examples include indolizinyl, isoindolyl, indolyl, indazolyl, purinyl, quinolizinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinazolinyl, cinnolinyl, pteridinyl, carbazolyl,

[0081] The "alkyl", "cycloalkyl", "alkenyl", "alkynyl", "heterocyclyl", "aryl" and "heteroaryl" may be substituted or unsubstituted; the substituents are not limited in any way, and common substituents include alkyl, alkyloxy, amino, nitro, cyano, amide, ester, halogen, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl and the like; when there are multiple substituents, the multiple substituents may be the same or different, and two adjacent substituents may be independent of each other or form a ring.

[0082] The amino group is -NR N1 R N2 , RN1 and R N2 The same or different, independently selected from H, C 1-10 Alkyl or C 6-10 The aryl group, the amino group is selected from, for example, N-methylamino, N-phenylamino, N,N-dimethylamino, N,N-diphenylamino, N-methyl-N-phenylamino and the like.

[0083] The amide group is -NH-C(O)-R N3 , where R N3 H, C 1-10 Alkyl, C 6-10 Aryl, such as R N3 It can be methyl, ethyl, propyl or butyl, etc.

[0084] The ester group is -C(O)OR N4 , where R N4 H, C 1-10 Alkyl, C 6-10 Aryl, such as R N4 It can be methyl, ethyl, propyl or butyl, etc.

[0085] The term "halogen" refers to fluorine, chlorine, bromine and iodine. DETAILED DESCRIPTION

[0086] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0087] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0088] Example 1

[0089] A. Palladium-Catalyzed Preparation of N-phenylmethanesulfonyl-N'-tert-butylphenyl-C-trifluoromethylamidine

[0090] Chemical name: N-phenylmethanesulfonyl-N'-tert-butyl-C-trifluoromethylamidine

[0091] Molecular formula: C 12 H 15 F3N2O2S

[0092]

[0093] Here’s how:

[0094] To a 10 ml reaction flask, Pd2(dba)3 (5.7 mg, 0.005 mmol), anhydrous tetrahydrofuran (1 mL), phenylmethylsulfonyl azide (40 mg, 0.22 mmol), and CsF (46 mg, 0.3 mmol) were added sequentially. The atmosphere was replaced with nitrogen. Tert-butyl isocyanide (17 mg, 0.20 mmol) and trifluoromethyltrimethylsilane (85 mg, 0.6 mmol) were then added via syringe. The reaction was allowed to proceed at room temperature (25°C) for 12 h. After the reaction was complete, the solvent was concentrated under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether:ethyl acetate = 3:1) to afford 51 mg of a pale yellow solid in 82% yield.

[0095] The characterization data of the obtained compound are as follows:

[0096] HRMS m / z(ESI+):309.0885[M+H] +

[0097] 1 H NMR (400MHz, cdcl3) δ8.00-7.89(m,2H),7.60-7.46(m,3H),6.20(s,1H),1.33(s,9H).

[0098] B. Rhodium-Catalyzed Preparation of N-phenylmethanesulfonyl-N'-tert-butylphenyl-C-trifluoromethylamidine

[0099] Here’s how:

[0100] To a 10 ml reaction flask, Rh(cod)acac (2.0 mg, 0.005 mmol), anhydrous tetrahydrofuran (1 mL), phenylmethylsulfonyl azide (40 mg, 0.22 mmol), and CsF (46 mg, 0.3 mmol) were added sequentially. The atmosphere was replaced with nitrogen. Tert-butyl isocyanide (17 mg, 0.20 mmol) and trifluoromethyltrimethylsilane (85 mg, 0.6 mmol) were then added via syringe. The reaction was allowed to proceed at room temperature (25°C) for 12 h. After completion of the reaction, the solvent was concentrated under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether:ethyl acetate = 3:1) to afford 45 mg of a pale yellow solid in a 73% yield.

[0101] C. Nickel-catalyzed preparation of N-phenylmethanesulfonyl-N'-tert-butylphenyl-C-trifluoromethylamidine

[0102] Here’s how:

[0103] To a 10 ml reaction flask were added [(Cy)3P]2NiCl2 (3.5 mg, 0.005 mmol), anhydrous tetrahydrofuran (1 mL), phenylmethylsulfonyl azide (40 mg, 0.22 mmol), and CsF (46 mg, 0.3 mmol). The atmosphere was replaced with nitrogen. Tert-butyl isocyanide (17 mg, 0.20 mmol) and trifluoromethyltrimethylsilane (85 mg, 0.6 mmol) were then added via syringe. The reaction was allowed to proceed at room temperature (25°C) for 12 h. After completion of the reaction, the solvent was concentrated under reduced pressure, and the residue was purified by flash column chromatography (petroleum ether:ethyl acetate = 3:1) to afford 12 mg of a pale yellow solid in a 19% yield.

[0104] Example 2-39

[0105] Example 2-39 was prepared using the same method as in Example 1. The specific raw material ratios are shown in Table 1.

[0106]

[0107] Table 1 Reaction temperature and specific raw material ratio of Examples 2-39

[0108]

[0109]

[0110] Note: a1: tris(dibenzylideneacetone)dipalladium;

[0111] b2: 4-methylphenylsulfonyl azide; b3: 4-methoxyphenylmethylsulfonyl azide; b4: 4-trifluoromethylphenylmethylsulfonyl azide; b5: 3-nitrobenzenemethylsulfonyl azide; b6: 4-bromophenylmethylsulfonyl azide; b7: 4-fluorophenylmethylsulfonyl azide; b8: 4-chlorophenylmethylsulfonyl azide; b9: 2-naphthalenesulfonyl azide; b10: 2-thiophenesulfonyl azide; b11: di-p-tolylphosphoryl azide; b12: diphenylphosphoryl azide; b13: dimethylphosphoryl azide;

[0112] b14: ​​p-Toluoyl azide; b15: 3-Fluorophenyl azide; b16: 4-Chlorophenyl azide; b17: 4-Bromophenyl azide; b18: 4-Methoxyphenyl azide; b19: 4-Trifluoromethoxy azide; b20: 4-Ethyl formate phenyl azide; b21: 3-Alkynylphenyl azide; b22: 1-Naphthyl azide;

[0113] b23: pentafluorophenyl azide; b24: 3-benzothiophene azide; b25: 2,6-dimethylphenyl azide; b26: 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonyl azide; b27: 2,3:4,5-bis-0-(1-methylethylidene)-β-D-fructopyranose azidesulfonate.

[0114] c1: tert-butyl isocyanide; c2: 2,6-dimethylphenyl isocyanide; c3: 2-tert-butylphenyl isocyanide;

[0115] d1: trifluoromethyltrimethylsilane; d2: pentafluoroethyltrimethylsilane; d3: difluoromethyltrimethylsilane;

[0116] The product names, yields and characterization results of Examples 1-39 are listed in Table 2.

[0117] Table 2

[0118]

[0119]

[0120]

[0121]

[0122]

[0123]

[0124]

[0125]

[0126]

[0127]

[0128] Biological Examples

[0129] Given that rice blast fungi typically infect plants via appressorium and can be cultivated indoors, the compounds of the present invention can be tested for their inhibition of conidia germination, germ tube growth, or appressorium formation using rice blast fungi as a model pathogen. The following examples illustrate the relevant activities of the compounds of the present invention.

[0130] Biological Example 1: Inhibitory Effects of C-Fluoroalkylamidine Compounds on Conidia Germination and Appressorium Formation of Magnaporthe grisea

[0131] a. Pathogen to be tested: Magnaporthe oryzae strain P131

[0132] b. Test method:

[0133] 1) Production of Rice Blast Conidia: The P. oryzae strain P131 to be tested is spotted onto a tomato oat agar plate (OTA) and cultured in a 28°C constant temperature and light incubator. After 3-5 days, the rice blast colonies on the OTA are fully disrupted and then evenly spread onto a new OTA and cultured in a 28°C constant temperature and light incubator. When new hyphae are visible growing on the surface of the culture medium (usually 1-2 days), gently disrupt the hyphae with a cotton swab, rinse with sterile water, and air dry. Cover the culture dish with a single layer of gauze and culture at 28°C under light for 48 hours to produce a large number of conidia on the surface of the OTA.

[0134] 2) Preparation of rice blast fungus conidia suspension: Elute the culture on OTA with sterile water and filter with three layers of lens cleaning paper. The filtrate is the conidia suspension. Use a hemocytometer to adjust the conidia concentration in the conidia suspension to 2×10 5 pieces / mL.

[0135] 3) The test compound was added to the conidia suspension at varying concentrations, yielding working concentrations of 200 ppm, 50 ppm, and 25 ppm. The solution was then spotted sequentially on hydrophobic glass slides. Four spots were placed on each slide, and the slides were kept in the dark and moisturized. Twelve hours after inoculation, the conidia germination rate and appressorium formation rate were observed and counted under a microscope.

[0136] 4) Statistics and Analysis: Count three inoculation points on each hydrophobic slide. Count the number of germinated conidia and appressorium formed in the center of each inoculation point (100). Calculate the average of these three data sets to determine the conidia germination rate and appressorium formation rate.

[0137] Table 3 shows the inhibitory effect of the compounds of the present invention on the conidia germination rate and appressorium formation rate of Rice blast fungus, wherein "+" represents an inhibitory effect of less than 40% at 200 ppm, "++" represents an inhibitory effect of more than 40% at 50 ppm, and "+++" represents an inhibitory effect of more than 70% at 25 ppm.

[0138] Table 3

[0139] Compound Conidia germination Appressorium formation 4 + + 6 + + 7 ++ + 10 + ++ 39 ++ +++

[0140] Biological Example 2: Preventive and therapeutic effects of C-fluoroalkyl amidine compounds on rice blast - Rice pot experiment

[0141] Preparation of rice: Prepare the susceptible variety Xiangwanxian 11, and place rice seedlings with four leaves and one heart in an inoculation box for use.

[0142] Production of Rice Blast Conidia: Pyricularia oryzae strain P131 is spotted onto tomato oat agar plates (OTAs) and cultured in a 28°C constant temperature and light incubator. After 3-5 days, the rice blast colonies on the OTA are fully disrupted and evenly spread onto new OTAs, which are then cultured in a 28°C constant temperature and light incubator. When new hyphae are visible growing on the surface of the culture medium (usually 1-2 days), gently disrupt the hyphae with a cotton swab, rinse with sterile water, and air dry. Cover the culture dish with a single layer of gauze and culture at 28°C under light for 48 hours to produce a large number of conidia on the surface of the OTA.

[0143] Prepare a conidia suspension of rice blast fungus: Elute the culture from the OTA with sterile water and filter through three layers of lens paper. The filtrate is the conidia suspension. Centrifuge at 5000 rpm for 5 minutes at room temperature. Suspend the precipitated conidia in gelatin and adjust the conidia concentration to 5 × 10 using a hemocytometer. 4 pieces / mL.

[0144] Preparation of test compound solution: Add the test compound stock solution to the prepared rice blast fungus conidia solution and dilute it to a working concentration of 200 ppm; dilute the test compound stock solution to a working concentration of 200 ppm.

[0145] Preventive Spray Inoculation: A mixture of rice blast fungus conidia and a small molecule agent was spray-inoculated onto susceptible rice variety Xiangwanxian 11, with 15 mL of the mixture sprayed per treatment. The plants were incubated in the dark for 36 hours, followed by normal culture. Seven days after inoculation, the preventive efficacy of the test compounds against rice blast was evaluated (Table 4).

[0146] Treatment spray inoculation: Rice cultivar Xiangwanxian 11 was spray-inoculated with conidia of the blast fungus. 15 mL of the small molecule agent was sprayed per treatment. The cells were incubated in the dark for 36 hours, followed by normal culture. Seven days after inoculation, the therapeutic efficacy of the test compounds against rice blast was evaluated (Table 5).

[0147] The rice blast disease survey was conducted in accordance with the agricultural industry standard "Technical Procedures for Field Monitoring of Rice Blast Resistance" (NYT3685-2020). The specific standards are as follows: Level 0: The entire leaf is disease-free; Level 1: There are needle-tip-sized brown necrotic spots on the leaves; Level 2: There are larger (1mm-2mm in diameter) brown necrotic spots on the leaves, but no typical lesions; Level 3: There are typical rice blast lesions, and the lesion area is <2%; Level 4: There are typical rice blast lesions, 2%≤lesion area<5%; Level 5: There are typical rice blast lesions, 5%≤lesion area<10%; Level 6: There are typical rice blast lesions, 10%≤lesion area<25%; Level 7: There are typical rice blast lesions, 25%≤lesion area<50%; Level 8: There are typical rice blast lesions, 50%≤lesion area<75%; Level 9: There are typical rice blast lesions, and the lesion area is ≥75%.

[0148] Table 4 Preventive effect of the compounds of the present invention on rice blast

[0149] Compound Disease level 4 4 6 4 7 2 10 3 39 1

[0150] Table 5 The therapeutic effect of the compounds of the present invention on rice blast

[0151] Compound Disease level 4 6 6 6 7 5 10 7 39 5

[0152] The above is an exemplary description of the implementation methods of the technical solution of the present invention. It should be understood that the scope of protection of the present invention is not limited to the above implementation methods. Any modifications, equivalent substitutions, improvements, etc. made by those skilled in the art within the spirit and principles of the present invention shall be included in the scope of protection of the claims of this application.

Claims

1. A method for preparing a compound represented by formula (I), comprising the following steps: The compound of formula (II), the compound of formula (III) and the compound of formula (IV) react in the presence of a catalyst and a fluoride salt to obtain a compound represented by formula (I); in, R 1 is selected from unsubstituted or optionally substituted with one, two or more R a Substituted groups of the following: phenylsulfonyl, naphthylsulfonyl, thienylsulfonyl; R 2 Selected from C 1-6 alkyl; R Si Selected from R Si1 、R Si2 、R Si3 The same or different, independently selected from C 1-6 alkyl; R F Selected from fluorinated C 1-6 alkyl; Each R a the same or different, independently selected from H, halogen, nitro, C 1-6 Alkyl, C 1-6 Alkyloxy, halogenated C 1-6 alkyl; The catalyst is selected from Pd2(dba)3, Rh(cod)acac, [(Cy)3P]2NiCl2; The fluoride salt is selected from potassium fluoride, sodium fluoride, and cesium fluoride.

2. The preparation method according to claim 1, characterized in that Each R a The same or different, independently selected from H, F, Cl, Br, methyl, methoxy, trifluoromethyl, nitro.

3. The preparation method according to claim 1, characterized in that R 1 is selected from phenylsulfonyl, 4-tolylsulfonyl, 4-methoxyphenylsulfonyl, 4-trifluoromethylphenylsulfonyl, 3-nitrophenylsulfonyl, 4-bromophenylsulfonyl, 4-fluorophenylsulfonyl, 4-chlorophenylsulfonyl, 2-naphthylsulfonyl, and / or, R 2 selected from tert-butyl; and / or, R Si Selected from trimethylsilyl, triethylsilyl, methyldiethylsilyl, triisopropylsilyl, tert-butyldimethylsilyl; and / or, R F Selected from trifluoromethyl, difluoromethyl, pentafluoroethyl.

4. The preparation method according to claim 1, characterized in that The compound of formula (II) is selected from phenylmethanesulfonyl azide, 4-methylphenylmethanesulfonyl azide, 4-methoxyphenylmethanesulfonyl azide, 4-trifluoromethylphenylmethanesulfonyl azide, 3-nitrobenzenemethylsulfonyl azide, 4-bromophenylmethanesulfonyl azide, 4-fluorophenylmethanesulfonyl azide, 4-chlorophenylmethanesulfonyl azide, 2-naphthalenesulfonyl azide, 2-thiophenesulfonyl azide; and / or, the compound of formula (III) is selected from tert-butyl isocyanide; And / or, the compound of formula (IV) is selected from trifluoromethyltrimethylsilane, pentafluoroethyltrimethylsilane, and difluoromethyltrimethylsilane.

5. The preparation method according to claim 1, characterized in that The molar ratio of the compound of formula (II), the compound of formula (III), and the compound of formula (IV) is (0.5-3):1:(0.8-5); and / or, the molar ratio of the catalyst to the compound of formula (II) is 0.001-5%; And / or, the molar ratio of the fluoride salt to the compound of formula (II) is (0.5-3):

1.

6. The preparation method according to claim 1, characterized in that The reaction is carried out in the presence of a solvent, and the solvent is selected from at least one of tetrahydrofuran, 1,4-dioxane, 2-methyltetrahydrofuran, dichloromethane, 1,2-dichloroethane, chloroform, ether, methyl n-butyl ether, methanol, ethanol, isopropanol, benzene, toluene, acetonitrile, nitromethane, pentane, and hexane; and / or, the reaction temperature of the reaction is selected from -10°C to 50°C; And / or, the reaction time of the reaction is selected from 2-24 hours.

7. The preparation method according to claim 1, characterized in that The molar ratio of the compound of formula (II), the compound of formula (III), and the compound of formula (IV) is (1.1-1.5):1:(1.5-3); and / or, the molar ratio of the catalyst to the compound of formula (II) is 0.05-5%; and / or, the molar ratio of the fluoride salt to the compound of formula (II) is (0.8-2):1; And / or, the reaction temperature of the reaction is selected from 20°C-30°C; And / or, the reaction time of the reaction is selected from 4-18 hours.

8. The compound represented by formula (I), its stereoisomers, tautomers, racemates or pesticide-acceptable salts thereof: in, R 1 、R 2 、R F Having the definition of any one of claims 1 to 3; The following compounds are not included:

9. The following compounds, their stereoisomers, tautomers, racemates or pesticide-acceptable salts:

10. Use of the compound according to claim 8 or 9, its stereoisomers, tautomers, racemates or pesticide-acceptable salts thereof in the preparation of a medicament for preventing or controlling rice blast.

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