Compounds with nematicidal activity and preparation methods and uses thereof

Abstract

The present invention relates to hydroxamic acid or hydrazide derivatives with nematicidal activity, as well as methods for their preparation and use. Specifically, the present invention discloses a compound represented by formula (I) or its optical isomers, cis-trans isomers, or pesticide-acceptable salts, and methods for their preparation. The compounds of the present invention have excellent nematicidal activity. #imgabs0#

Description

Technical Field

[0001] The present invention belongs to the field of pesticides and specifically relates to a hydroxamic acid or hydrazide derivative having nematicidal activity, a preparation method thereof, and uses thereof. Background Art

[0002] Plant parasitic nematodes are a type of extremely harmful pathogenic microorganisms that can infect a variety of economic crops. For example, root-knot nematodes can infect economic crops such as cucumbers, peanuts, citrus, tomatoes, eggplants, and watermelons. Due to nematode damage, direct losses of grain and fiber crops can reach 12%, and losses of vegetables and fruit trees can exceed 20%.

[0003] Nematodes absorb nutrients from plants, impacting their normal growth. This leads to weak plant growth, yellowing leaves, poor fruit tree growth, and underdeveloped roots, further impairing nutrient absorption. Due to the plant's sluggish growth and poor resistance, the incidence of other pests and diseases increases dramatically, and the plant's ability to withstand natural disasters also decreases. In addition to causing diseases themselves, some nematodes can also spread other diseases, such as bacterial, viral, and fungal diseases. Numerous other pathogens exist in the soil, and once nematodes infect the roots, they are susceptible to infection by other pathogens, exacerbating the occurrence of diseases.

[0004] In agriculture, root-knot nematodes are primarily controlled through physical and chemical means. Scientific crop rotation can significantly reduce the severity of root-knot nematodes. In addition, crop rotation with water and land, or crop rotation with disease-resistant vegetables such as green onions, leeks, and peppers, can also be used. Physical methods such as high-temperature greenhouses, flooding, lime nitrogen, ultrasound, and radiation can also be used to kill nematodes. However, the most effective control method is the use of chemical pesticides for nematicidal destruction. Pesticides used to control root-knot nematodes primarily include fumigants and non-fumigants. Fumigants include carbon disulfide, dichloropropane, dichloropropylene, methyl iodide, and methyl bromide. However, most of these are highly harmful to the environment and mammals, and some have been banned. Non-fumigant nematicides primarily include organophosphates, carbamates, chloropicrin, dazomethon, methamphetamine, furfural, acetofenapyr, trifluanidamide, fluthiazolinone, tioxazafen, and abamectin. However, compared with insecticides, fungicides and herbicides, the available varieties of nematicides are still too few. Therefore, the invention of novel chemical nematicides with high efficiency, low toxicity and good environmental compatibility has become a technical problem that urgently needs to be solved in this field.

[0005] In summary, there is an urgent need in the art to develop new compounds with nematicidal activity. Summary of the Invention

[0006] The purpose of the present invention is to provide a novel compound with nematicidal activity, a preparation method and an application thereof, wherein the compound should have the characteristics of high efficiency, low toxicity and good environmental compatibility.

[0007] In a first aspect, the present invention provides a compound represented by formula (I), or an optical isomer, a cis-trans isomer, or a pesticide-acceptable salt thereof:

[0008]

[0009] Where,

[0010] Ring A is substituted or unsubstituted C 5-10 Aromatic ring, substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 5-10 Aromatic heterocycle, substituted or unsubstituted C 3-12 Carbocyclic, substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 3-12 carbon heterocycles;

[0011] Ring B is a substituted or unsubstituted saturated or unsaturated C containing 1-3 heteroatoms independently selected from O, N or S 5-10 carbon heterocycles;

[0012] Ring A and Ring B are connected by a single bond or in a fused form;

[0013] X is independently: N, O or absent (preferably N or O);

[0014] Y is independently: hydrogen, halogen (preferably fluorine, chlorine; more preferably fluorine);

[0015] G is independently one or more (preferably 1-3, more preferably 1-2) groups selected from the group consisting of H, halogen, nitro, cyano, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkyl, C 1-6 Haloalkyl, substituted or unsubstituted C 3-10 Cycloalkyl, substituted or unsubstituted C 1-6 Silyl, substituted or unsubstituted C 1-6 Alkylthio, substituted or unsubstituted C 2-6 Alkenyl, substituted or unsubstituted C 2-6 Alkynyl, substituted or unsubstituted amino, substituted or unsubstituted C 5-10 Aryl, substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 5-10 heteroaryl, substituted or unsubstituted aldehyde, substituted or unsubstituted amide, substituted or unsubstituted sulfonate, substituted or unsubstituted C 2-6Ester group; or, two or more G and the carbon atom to which they are attached together constitute a substituted or unsubstituted C 3-6 Carbocyclic, or substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 3-6 Carbon heterocycle.

[0016] In a specific embodiment,

[0017] The structural unit Having a structure selected from the following:

[0018]

[0019] Wherein, Z is independently selected from: hydrogen, substituted or unsubstituted C 1-6 Alkyl, C 1-6 Haloalkyl (preferably trifluoromethyl), cyano, substituted or unsubstituted amino, substituted or unsubstituted C 5-10 Aromatic ring, substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 5-10 Aromatic heterocycle.

[0020] In a specific embodiment,

[0021] The structural unit Select from the following structures:

[0022]

[0023] Wherein, Z is as described above.

[0024] In a specific embodiment,

[0025] The structural unit Having a structure selected from the following:

[0026]

[0027] In a specific embodiment,

[0028] The structural unit Select from the following structures:

[0029]

[0030] In a specific embodiment, the compound is represented by the following formula:

[0031]

[0032] Wherein, Z is as described above; and

[0033] G is as described above.

[0034] In a specific embodiment, the present invention provides a compound selected from the group consisting of:

[0035]

[0036]

[0037]

[0038]

[0039]

[0040]

[0041]

[0042]

[0043]

[0044]

[0045]

[0046]

[0047]

[0048]

[0049]

[0050]

[0051]

[0052] In a specific embodiment, the compound is represented by the following formula:

[0053]

[0054] In the formula, G is independently one or more (preferably 1-3, more preferably 1-2) groups selected from the following groups: H, halogen, nitro, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkyl, C 1-6 Halogenated alkyl.

[0055] In a specific embodiment, the compound is selected from:

[0056]

[0057]

[0058]

[0059] More preferably, the compound is Compound A16.

[0060] In a second aspect, the present invention provides an agricultural composition, characterized in that it comprises: 0.001-99.00wt% of the compound described in the first aspect, or the optical isomers, cis-trans isomers or pesticide-acceptable salts of the compound, or a combination thereof, and a pesticide-acceptable carrier and / or excipient.

[0061] In a third aspect, the present invention provides the use of the compound described in the first aspect, or the optical isomers, cis-trans isomers or pesticide-acceptable salts of the compound, or the agricultural composition described in the second aspect, for killing or preventing nematodes or for preparing a nematicide for killing or preventing nematodes.

[0062] In a preferred embodiment, the present invention provides the compound described in the first aspect, or the optical isomers, cis-trans isomers or pesticide-acceptable salts of the compound, or the agricultural composition described in the second aspect, for killing or preventing nematodes or for preparing a nematicide for killing or preventing nematodes.

[0063] In a fourth aspect, the present invention provides a method for killing or preventing nematodes, the method comprising applying an effective amount of the compound described in the first aspect, or the optical isomers, cis-trans isomers or pesticide-acceptable salts of the compound, or the agricultural composition described in the second aspect to an area where nematodes need to be killed or prevented.

[0064] In a preferred embodiment, the nematodes include, but are not limited to: root-knot nematodes, such as Meloidogyne arenaria, Meloidogyne chitwoodi, Meloidogyne exigua, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, and other Meloidogyne species; cyst nematodes, such as Globodera rostochiensis, Globodera aallida, Globodera tabacum, and other Globodera species; Heterodera, such as Heterodera avenae, Heterodera glycines, Heterodera exigua, and other Globodera species. schachtii), clover cyst nematode (Heterodera trifolii), and other Heterodera species; tumor nematodes, such as Anguina funesta, Anguina tritici, and other Anguina species; stem and leaf bud nematodes, such as Aphelenchoides besseyi, Aphelenchoides fragariae, Aphelenchoides ritzemabosi, and other Aphelenchoides species; thorn nematodes, such as Belonolaimus longicaudatus and other Belonolaimus species; pine nematodes, such as Bursaphelenchus xylophilus and other Bursaphelenchus species; ring nematodes, such as Criconema, Criconemella, Criconemoides, and Mesocriconema; bulb nematodes, such as Ditylenchus destructor, Ditylenchus dipsaci, Ditylenchus myceliophagus, and other Ditylenchus species;Cone nematodes, such as Dolichodorus; spiral nematodes, such as Helicotylenchus dihystera, Helicotylenchus multicintus, and other Helicotylenchus; sheath nematodes, such as Hemicycliophora and Hemicriconemoides; crown nematodes, such as Hoploaimus columbus and other Hoploaimus; pseudorhizobium nematodes, such as Nacobbus aberrans and other Nacobbus; needle nematodes, such as Longidorus spp. elongatus and other Longidorus species; nailing nematodes, such as Paratylenchus; root rot nematodes, such as Pratylenchus brachyurus, Pratylenchus coffee, Pratylenchus zeae, Pratylenchus penetrans, and other Pratylenchus species; boring nematodes, such as Radopholus similis and other Radopholus species; reniform nematodes, such as Rotylenchus robustus and other Rotylenchus species; stump nematodes, such as Trichodorus primitivus and other Trichodorus species; dwarf nematodes such as Tylenchorhynchus claytoni, Tylenchorhynchus dubius, and other Tylenchorhynchus species; citrus nematodes such as Tylenchulus semipenetrans and other Tylenchulus species; Xiphinema such as Xiphinema americanum, Xiphinema index, Xiphinema diversicaudatum, and other Xiphinema species; preferably, Meloidogyne incognita.

[0065] In a fifth aspect, the present invention provides a method for preparing the compound of the first aspect, or the optical isomers, cis-trans isomers, or pesticide-acceptable salts of the compound, characterized in that:

[0066] The reaction process of the preparation method is as follows:

[0067]

[0068]

[0069] Differently substituted anthranilic acid methyl esters 1 react with hydroxylamine hydrochloride under alkaline conditions to obtain open-chain hydroxamic acid derivatives 2. Compound 2 is then diazotized or ring-closed with triphosgene, formic acid, acetic anhydride, etc. to obtain hydroxamic acid derivatives. Compound 3 is then reacted with compound 4 under alkaline conditions to obtain the target compound 5.

[0070] Alternatively, the reaction process of the preparation method is as follows:

[0071]

[0072] wherein R1 is methyl or trifluoromethyl; the differently substituted anthranilic acid raw material 6 reacts with trifluoroacetic anhydride or acetic anhydride under reflux conditions to obtain compound 7, and then compound 7 is reacted with hydrazine hydrate ethanol under reflux conditions to obtain compound 8, and then compound 8 reacts with raw material 4 under alkaline conditions to obtain the target compound 9;

[0073] Alternatively, the reaction process of the preparation method is as follows:

[0074]

[0075] Among them, compound 10 and compound 11 can be heated with acetonitrile and potassium carbonate to obtain target compound 12.

[0076] In a preferred embodiment, the reaction of compound 10 and compound 11 needs to be carried out in the presence of an inert solvent and a base. Commonly used inert solvents include: acetonitrile, dichloromethane, dichloroethane, acetone, chloroform, ethanol, methanol, N,N-dimethylformamide, N,N-dimethylacetamide, dioxane, etc. Commonly used bases include inorganic bases and organic bases, such as but not limited to: sodium hydroxide, potassium hydroxide, potassium carbonate, cesium carbonate, DBU, triethylamine, N,N-diisopropylethylamine, sodium hydride, sodium tert-butoxide, potassium tert-butoxide, lithium diisopropylamide, sodium amide, etc.

[0077] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. DETAILED DESCRIPTION

[0078] After extensive and in-depth research, the inventors unexpectedly discovered a series of novel trifluorobutene hydroxamic acid or hydrazide derivatives with significant nematicidal activity. These compounds possess high efficacy, low toxicity, and good environmental compatibility, making them suitable for nematode control. This work led to the completion of the present invention.

[0079] Group Definition

[0080] The terms used herein have the same or similar meanings as those commonly understood by those skilled in the art. For the sake of clarity only, some of the terms used herein are defined as follows.

[0081] As used herein, all groups are preceded by "C 1-n ” and other modifiers describe the number of carbon atoms in the group. For example, “C 1-6 " means that the group it modifies has 1 to 6 carbon atoms.

[0082] As used herein, the term "alkyl" refers to a straight or branched chain alkyl group, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, or the like. The term "alkenyl" refers to a straight or branched chain alkenyl group, such as vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, or the like. The term "alkynyl" refers to a straight or branched chain alkynyl group, such as ethynyl, propynyl, or the like.

[0083] Similarly, the term "cycloalkyl" refers to a cyclic alkyl group, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or the like. The term "cycloalkenyl" refers to a cyclic alkenyl group having one or more double bonds, such as cyclopentenyl, cyclohexenyl, cycloheptenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, or the like.

[0084] As used herein, the term "alkoxy" refers to a straight or branched chain alkoxy group, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, or the like.

[0085] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. The term "halogenated" refers to a group substituted by the same or different one or more of the above halogen atoms, for example trifluoromethyl, trifluoromethoxy, difluoromethyl, monofluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.

[0086] The term "ring" or "ring system" refers to a carbocyclic or heterocyclic ring.

[0087] The term "heterocycle" refers to an atom in which at least one of the atoms forming the heterocycle skeleton is not carbon but is nitrogen, oxygen or sulfur. Typically, the heterocycle contains no more than 4 nitrogen atoms, no more than 2 oxygen atoms and or no more than 2 sulfur atoms. Unless otherwise indicated, the heterocycle may be a saturated, partially unsaturated or fully unsaturated ring.

[0088] The term "fused ring system" refers to two or more rings fused together.

[0089] As used herein, the term "heterocyclyl" refers to a ring containing one or more heteroatoms selected from nitrogen, oxygen or sulfur, for example, pyridyl, thiazolyl, isothiazolyl, thienyl, furanyl, pyrrolyl, pyrazolyl, pyrimidinyl, tetrahydrofuranyl, 4,5-dihydrothiazol-2-yl, 2-cyanoimino-4-oxo-1-yl, 3-thiazolidin-3-yl, 2-cyanoimino-4-oxo-1-yl, 3-thiazin-3-yl, oxazolyl, isoxazolyl, 1H-tetrazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl or tetrazolyl, etc.

[0090] The term "heterocycle" refers to a ring system wherein at least one of the rings is a heterocycle.

[0091] The term "heteroaromatic ring" refers to a ring system in which at least one ring is aromatic.

[0092] Unless otherwise specified as "substituted or unsubstituted", the groups of the present invention may be substituted by substituents selected from the following groups: halogen, cyano, nitro, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Halogenated alkenyl, C 2-6 Alkynyl, C 2-6 Haloalkynyl, hydroxyl C 1-4 Alkyl, C 1-6alkyl, alkylamino, alkyloxy, alkylthio, alkyloxy, alkylthio, heteroalkylthio, cycloalkylthio, halogenated alkylthio, heterocycloalkylthio, arylthio, heteroarylthio, alkylamino, alkoxyamino, halogenated alkylamino, heteroalkylamino, cycloalkylamino, heterocycloalkylamino, arylamino, heteroarylamino, alkylsulfoxide, alkoxysulfoxide, halogenated alkylsulfoxide, cycloalkylsulfoxide, heterocycloalkylsulfoxide, sulfone, arylsulfoxide, heteroarylsulfoxide, alkylsulfone, alkoxysulfone, haloalkylsulfone, heteroalkylsulfone, cycloalkylsulfone, heterocycloalkylsulfone, arylsulfone, heteroarylsulfone, carbonyl, alkylcarbonyl, alkoxycarbonyl, heteroalkoxycarbonyl, heteroalkylcarbonyl, cycloalkylcarbonyl, heterocycloalkylcarbonyl, haloalkylcarbonyl, arylcarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyl, arylalkylcarbonyl, heteroarylalkylcarbonyl, bridged ring substituent, spiro ring substituent.

[0093] Inert solvents refer to various solvents that do not react with raw materials, including various linear, branched or cyclic alcohols, ethers or ketones, halogenated alkanes, 1,4-dioxane, acetonitrile, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, etc.

[0094] The compounds of the present invention may contain one or more asymmetric centers and thus occur as racemates, racemic mixtures, single enantiomers, diastereomeric compounds, and single diastereomers. The presence of asymmetric centers depends on the nature of the various substituents on the molecule. Each such asymmetric center will independently produce two optical isomers, and all possible optical isomers and diastereomeric mixtures and pure or partially purified compounds are included within the scope of the present invention. The present invention includes all isomeric forms of the compounds.

[0095] Based on the teachings of the present invention and common knowledge in the art, those skilled in the art will understand that the various groups in the compounds of the present invention can be further substituted to obtain derivatives that have the same or similar activity as the compounds specifically disclosed in the present invention. The various groups in the compounds of the present invention can be substituted with various substituents conventional in the art, as long as such substitution does not violate the rules of chemical synthesis or valence rules.

[0096] As used herein, the term "substituted" refers to the replacement of one or more hydrogen atoms on a specific group with a specific substituent. The specific substituent may be a substituent described above, a specific substituent described in the examples, or a conventional substituent in the art. Therefore, in the present invention, the substituents in the general formula may also independently be the corresponding groups in the specific compounds described in the examples; that is, the present invention encompasses both combinations of the substituents in the general formula and combinations of some of the substituents shown in the general formula with other specific substituents described in the examples. Preparing compounds with such substituent combinations and testing the resulting compounds for activity are readily accomplished by those skilled in the art using conventional techniques. In other words, based on the teachings of the present invention, those skilled in the art are able to synthesize a variety of compounds falling within the scope of the present invention. These compounds are not limited to the specific compounds disclosed in the examples; the compounds of the present invention include the specific compounds disclosed in the examples as well as various compounds composed of specific substituents at certain positions in these specific compounds and substituents at other positions in the general formula. Due to space limitations, these compounds are not listed here.

[0097] Compounds having nematicidal activity of the present invention

[0098] The term "active substance of the present invention" or "active compound of the present invention" refers to the compound represented by the general formula (I), its optical isomers, cis-trans isomers or pesticidally acceptable salts.

[0099] The term "pesticide-acceptable salt" refers to a salt whose anion is known and acceptable to form a pharmaceutically acceptable salt of a nematicide. Preferably, the salt is water-soluble. Suitable acid salts formed from the compound of formula (I) include salts formed from inorganic acids, such as hydrochlorides, phosphates, sulfates, and nitrates; and salts formed from organic acids, such as acetates and benzoates.

[0100] The active substance of the present invention can be used to control and eliminate a wide range of plant parasitic nematodes in agriculture and forestry. In this specification, "nematicide" is a general term for substances that have the effect of preventing and controlling all plant parasitic nematodes mentioned herein.

[0101] Examples of plant parasitic nematodes include, but are not limited to, root-knot nematodes, such as Meloidogynearenaria, Meloidogyne chitwoodi, Meloidogyne exigua, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica, and other Meloidogyne species; cyst nematodes, such as Globodera rostochiensis, Globodera pallida, Globodera tabacum, and other Globodera species; Heterodera, such as Heterodera avenae, Heterodera spp. glycines), beet cyst nematodes (Heteroderaschachtii), clover cyst nematodes (Heterodera trifolii), and other Heterodera species; tumor nematodes, such as Anguina funesta, Anguina tritici, and other Anguina species; stem and leaf bud nematodes, such as Aphelenchoides besseyi, Aphelenchoides fragariae, Aphelenchoides ritzemabosi, and other Aphelenchoides species; thorn nematodes, such as Belonolaimus longicaudatus and other Belonolaimus species; pine nematodes, such as Bursaphelenchus xylophilus xylophilus and other Bursaphelenchus species; ring nematodes, such as Criconema, Criconemella, Criconemoides, and Mesocriconema; bulb nematodes, such as Ditylenchus destructor, Ditylenchus dipsaci, Ditylenchus myceliophagus, and other Ditylenchus species;Cone nematodes, such as Dolichodorus; spiral nematodes, such as Helicotylenchus dihystera, Helicotylenchus multicintus, and other Helicotylenchus; sheath nematodes, such as Hemicycliophora and Hemicriconemoides; crown nematodes, such as Hoploaimus columbus and other Hoploaimus; pseudorhizobium nematodes, such as Nacobbus aberrans and other Nacobbus; needle nematodes, such as Longidorus spp. elongatus and other Longidorus species; nailing nematodes, such as Paratylenchus; root rot nematodes, such as Pratylenchus brachyurus, Pratylenchus coffee, Pratylenchus zeae, Pratylenchus penetrans, and other Pratylenchus species; boring nematodes, such as Radopholus similis and other Radopholus species; reniform nematodes, such as Rotylenchus robustus and other Rotylenchus species; stump nematodes, such as Trichodorus primitivus and other Trichodorus species; dwarf nematodes such as Tylenchorhynchus claytoni, Tylenchorhynchus dubius, and other Tylenchorhynchus species; citrus nematodes such as Tylenchulus semipipenetrans and other Tylenchulus species; Xiphinema species such as Xiphinema americanum, Xiphinema index, Xiphinema diversica udatum, and other Xiphinema species.

[0102] The compound of the present invention has a good control effect on the southern root-knot nematode (Meloidogyne incognita).

[0103] Based on the teachings of the present invention, those skilled in the art will understand that the compounds of the present invention are compounds with pesticide activity and can be used as pesticides. As compounds with pesticide activity, the compounds of the present invention should naturally also possess the various inherent properties of pesticides. For example, the compounds of the present invention have excellent killing activity against insects that need to be killed, such as nematodes, but the compounds of the present invention are safe for species other than the insects that need to be killed, such as mammals (including but not limited to humans, livestock, poultry), beneficial insects, or insects of economic value (including but not limited to bees and silkworms); or, they also have a certain killing effect on insects other than the nematodes that need to be killed, such as Lepidoptera, Hemiptera, and Coleoptera pests, such as agricultural and forestry pests: aphids, plant lice, whiteflies, leafhoppers, thrips, cotton bollworms, cabbage worms, diamondback moths, Spodoptera litura, armyworms, etc.; and so on. Those skilled in the art can use various well-known technical means to test and obtain the above-mentioned properties of the compounds of the present invention, which will not be elaborated here.

[0104] A nematicide composition containing the active substance of the present invention.

[0105] The active substances of the present invention can be prepared into nematicide compositions by conventional methods. These active compounds can be made into conventional formulations, such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with the active substance, microcapsules in polymers, coating compounds for seeds, and formulations for use with combustion devices, such as fumigation cartridges, fumigation pots, and fumigation trays, as well as ULV cold mist and hot mist formulations.

[0106] These formulations can be produced by known methods, for example, by mixing the active compound with an extender, i.e., a liquid, liquefied gas, or solid diluent or carrier, and optionally a surfactant, i.e., an emulsifier and / or dispersant and / or foam former. When, for example, water is used as the extender, an organic solvent may also be used as an auxiliary agent.

[0107] When a liquid solvent is used as a diluent or carrier, it is basically suitable, such as: aromatic hydrocarbons, for example xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, for example chlorobenzene, vinyl chloride or methylene chloride; aliphatic hydrocarbons, for example cyclohexane or paraffin, for example mineral oil fractions; alcohols, for example ethanol or ethylene glycol and their esters and esters; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or less commonly used polar solvents, for example dimethylformamide and dimethyl sulfoxide, and water.

[0108] A diluent or carrier for liquefied gas refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide.

[0109] Solid carriers can be ground natural minerals such as kaolin, clay, talc, quartz, attapulgite, montmorillonite, or diatomaceous earth; and ground synthetic minerals such as highly dispersed silicic acid, alumina, and silicates. Solid carriers for particles are crushed and graded natural zircons such as calcite, marble, pumice, sepiolite, and dolomite, as well as particles synthesized from inorganic and organic coarse powders, and particles of organic materials such as sawdust, coconut shells, corn cobs, and tobacco stems.

[0110] Nonionic and anionic emulsifiers can be used as emulsifiers and / or foam formers. Examples include polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, such as alkylaryl polyethylene glycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates, and albumin hydrolysates. Dispersants include lignin sulfite wastewater and methylcellulose.

[0111] Binders such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or emulsions, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, may be used in the formulations.

[0112] Colorants such as inorganic dyes, such as iron oxide, cobalt oxide and Prussian blue; organic dyes, such as azo dyes or metal cyanine dyes; and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, aluminum and zinc, etc. can be used.

[0113] The active compounds of the present invention may be prepared as a mixture with other active compounds and present in their commercial preparations or in dosage forms prepared from these preparations. These other active compounds are insecticides, bactericides, fungicides, herbicides, growth control agents, etc. Insecticides include, for example, phosphates, carbamates, chlorinated hydrocarbons, and substances produced by microorganisms, such as abamectin, and fungicides include strobilurins, amides, triazoles, etc.

[0114] In addition, the active compounds of the present invention may also be mixed with synergists in their commercial preparations or in dosage forms prepared from these preparations. These synergists are compounds that enhance the effects of the active compounds. Since the active compounds themselves are active, it is not necessary to add synergists.

[0115] These formulations typically contain 0.001-99.99% by weight, preferably 0.01-99.9% by weight, and more preferably 0.05-90% by weight of the active compound of the present invention, based on the total weight of the nematicidal composition. The concentration of the active compound in commercial formulations or dosage forms can vary over a wide range. The concentration of the active compound in the dosage form can range from 0.0000001 to 100% (g / v), preferably between 0.0001 and 1% (g / v).

[0116] The compounds of the present invention can be prepared by the following method, however, the conditions of the method, such as the reactants, solvent, base, amount of the compound used, reaction temperature, reaction time, etc. are not limited to the following explanation. The compounds of the present invention can also be conveniently prepared by optionally combining various synthetic methods described in this specification or known in the art. Such combinations can be easily performed by those skilled in the art. Where feasible, the reagents can be purchased through commercial sources.

[0117] Typical embodiments of the compounds of the present invention can be synthesized using the following general reaction schemes. It is apparent from the descriptions given herein that the general schemes can be modified by replacing other materials with similar structures to obtain corresponding different products. Synthetic methods can be used to provide large-scale production as needed. Raw materials can be obtained by commercial methods or synthesized using disclosed methods. The examples given herein generally make the characteristics of the necessary raw materials apparent through simple test steps.

[0118] Building-up reaction parameters can use, for example, following general method and procedure, prepare compound of the present invention from the starting material that is easily obtained.Will recognize that in the situation that provides typical or optimization method conditions (that is, reaction temperature, time, the molar ratio of reactant, solvent, catalyst, pressure etc.), also other method conditions can be used, unless otherwise noted.Optimum reaction conditions can change with used specific reactant or solvent, but such conditions can be determined by conventional optimization program by those skilled in the art.

[0119] The starting materials for the following reactions are generally known compounds or can be prepared by known procedures or obvious modifications thereof. For example, many starting materials can be obtained from commercial suppliers, while others can be prepared by procedures described in standard reference texts or obvious modifications thereof.

[0120] In the preparation method of the present invention, each reaction is usually carried out in an inert solvent at a reaction temperature of -20-120°C (preferably -10-0°C, 20-30°C, or 80-100°C). The reaction time is usually 2-24 hours, preferably 4-18 hours. The reaction time can be appropriately extended according to the reaction requirements, and the specific reaction time is determined according to the degree of reaction.

[0121] The base used in the reaction includes (but is not limited to): triethylamine, diisopropylethylamine, diethylamine, piperidine, piperazine, morpholine, N-methylmorpholine, triethylenediamine (DABCO), 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), 1,5-diazabicyclo[4,3,0]non-5-ene (DBN), potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, or a combination thereof. In the scheme, the intermediate is synthesized by conventional methods, and then reacted through the part containing a leaving group to obtain the corresponding final product.

[0122] Advantages of the present invention:

[0123] 1. The nematode active compound of the present invention has a novel structure, thus laying a material foundation for the development of new nematode control pesticides;

[0124] 2. The nematicidal active compound of the present invention is highly effective, low in toxicity, and has good environmental compatibility;

[0125] 3. The nematicidal compounds of the present invention have broad-spectrum nematicidal activity.

[0126] The technical solutions of the present invention are further described below with reference to specific examples. However, the following examples do not constitute a limitation of the present invention. All various application methods adopted in accordance with the principles and technical means of the present invention are within the scope of the present invention. Experimental methods in the following examples, where specific conditions are not specified, are generally carried out under conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight.

[0127] Example 1: Preparation of 3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A1

[0128] 1.1 Preparation of 2-amino-N-hydroxybenzamide (I-2)

[0129]

[0130] Sodium hydroxide (80 mmol) was added to a 100 mL round-bottom flask. Water (20 mL) was added and stirred to dissolve it. Then, 40 mmol of hydroxylamine hydrochloride was added and stirred for 5 minutes. Then, a solution of methyl anthranilate (20 mmol) in methanol (20 mL) was added to the flask and stirred at room temperature for 10 hours. After the reaction was completed, the methanol in the reaction solution was removed by rotary evaporation and the pH of the reaction solution was adjusted to 6-7 with 2 mol / L hydrochloric acid. A large amount of solid precipitated, which was filtered and the filter cake was washed with a small amount of ice water. It was dried in an infrared oven to obtain a pure product. The spectral data of the representative compounds are as follows: 2-amino-N-hydroxybenzamide: white solid, yield 24%; 1 H NMR (400MHz, DMSO-d6) δ10.91(s,1H),8.83(s,1H),7.32(d,J=7.2Hz,1H),7.18–7.03(m,1H),6.77–6.63(m,1H),6.56–6.42(m,1H),6.22(s,2H)ppm. 13 C NMR (101MHz, DMSO-d6) δ166.96,149.18,131.56,127.49,116.18,114.71,113.13ppm.

[0131] 1.2 Preparation of 3-hydroxybenzo[d][1,2,3]triazine-4(3H)-one (I-3)

[0132]

[0133] Disperse the substituted 2-amino-N-hydroxybenzamide (5 mmol) in water (10 mL), add concentrated hydrochloric acid (2 mL), and add sodium nitrite (10 mmol) in water (10 mL) dropwise while stirring in an ice bath. After the addition is complete, continue the reaction in an ice bath for 1 hour. A solid precipitates, which is filtered, washed with a small amount of ice water, and dried under infrared irradiation to yield the pure product. A white solid is obtained with a yield of 51%. 1 H NMR (400MHz, DMSO-d6) δ12.91(s,1H),8.26(dd,J=8.0,0.8Hz,1H),8.20(d,J=8.0Hz,1H),8.12–8.02(m,1H),7.96–7.86(m,1H)ppm. 13 C NMR (101MHz, DMSO-d6) δ150.96,143.79,135.00,132.40,128.02,124.67,121.17ppm.

[0134] 1.3 Preparation of 3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one (A1)

[0135]

[0136] Sodium hydroxide (4 mmol), 3-hydroxybenzo[d][1,2,3]triazine-4(3H)-one (2 mmol), 4-bromo-1,1,2-trifluoro-1-butene (6 mmol), and DMF (15 mL) were added to a 50 mL eggplant-shaped flask in sequence and heated to 75°C for overnight reaction. After the reaction, 20 mL of water was added to the flask. The aqueous phase was extracted three times with ethyl acetate (20 mL x 3). The organic phase was washed three times with saturated sodium chloride solution (30 mL x 3). The organic phase was collected and dried over anhydrous Na2SO4, filtered, concentrated, and dried with an appropriate amount of silica gel powder. The product was then dry-loaded and purified by column chromatography to obtain the pure product. The product was a yellow liquid with a yield of 55%. 1 H NMR (400MHz, CDCl3) δ8.36 (dd, J=8.0, 1.6Hz, 1H), 8.19 (d, J=8.4Hz, 1H), 8.04 –7.92(m,1H),7.87–7.76(m,1H),4.59(t,J=6.6Hz,2H),3.00–2.83(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.90–-102.58(m,1F),-121.89–-122.78(m,1F),-175.27–-176.08(m,1F)ppm. 13 C NMR(101MHz,CDCl3)δ153.74(ddd, 1 J CF =287.2,274.8Hz, 2 J CF =45.8Hz),150.89(s),144.17(s),135.18(s),132.52(s),128.87(s),125.53(s),125.26(ddd, 1 J CF =234.7Hz, 2 J CF =53.7,17.6Hz),122.25(s),73.20(s),25.40(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz)ppm.HRMS(ES+)calcd for C 11 H8F3N3NaO2(M+Na) + ,294.0466,found,294.0467.

[0137] Example 2: Preparation of 6-methyl-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A3

[0138] 2.1 Preparation of 2-amino-N-hydroxy-5-methylbenzamide (I-8)

[0139]

[0140] Sodium hydroxide (80 mmol) was added to a 100 mL round-bottom flask. Water (20 mL) was added and stirred to dissolve. Then, 40 mmol of hydroxylamine hydrochloride was added and stirred for 5 minutes. A solution of methyl 2-amino-3-methylbenzoate (20 mmol) in methanol (20 mL) was then added to the flask and stirred at room temperature for 10 hours. After the reaction was completed, the methanol in the reaction solution was removed by vortexing, and the pH of the reaction solution was adjusted to 6-7 with 2 mol / L hydrochloric acid. A large amount of solid precipitated, which was filtered, and the filter cake was washed with a small amount of ice water and dried in an infrared oven to obtain the pure product. A white solid with a yield of 31% was obtained. 1 H NMR (400MHz, DMSO-d6) δ10.84(s,1H),8.79(s,1H),7.14(s,1H),6.96(d,J=8.0Hz,1H),6.61(d,J=8.0Hz,1H),5.99(s,2H),2.13(s,3H)ppm. 13 C NMR (101MHz, DMSO-d6) δ166.99,146.85,132.34,127.53,123.05,116.33,113.23,19.96ppm.

[0141] 2.2 Preparation of 3-hydroxy-6-methylbenzo[d][1,2,3]triazine-4(3H)-one (I-10)

[0142]

[0143] Disperse the substituted 2-amino-N-hydroxy-5-methylbenzamide (5 mmol) in water (10 mL). Add concentrated hydrochloric acid (2 mL). Add sodium nitrite (10 mmol) in water (10 mL) dropwise while stirring on ice. After the addition is complete, continue the reaction on ice for 1 hour. A solid precipitates, which is filtered, washed with a small amount of ice water, and dried under infrared irradiation to obtain the pure product. A gray solid is obtained with a yield of 46%. 1 H NMR (400MHz, DMSO-d6) δ12.82 (s, 1H), 8.13–8.00 (m, 2H), 7.88 (d, J = 8.4Hz, 1H), 2.54 (s, 3H) ppm.13 C NMR (101MHz, DMSO-d6) δ150.91,143.32,142.15,136.28,127.91,123.79,121.07,21.21ppm.

[0144] 2.3 Preparation of 6-methyl-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazin-4(3H)-one (A3)

[0145]

[0146] Sodium hydroxide (4 mmol), 3-hydroxy-6-methylbenzo[d][1,2,3]triazine-4(3H)-one (2 mmol), 4-bromo-1,1,2-trifluoro-1-butene (6 mmol), and DMF (15 mL) were added to a 50 mL eggplant-shaped flask in sequence and heated to 75°C for overnight reaction. After the reaction was complete, 20 mL of water was added to the reaction flask. The aqueous phase was extracted three times with ethyl acetate (20 mL x 3). The organic phases were combined and washed three times with saturated sodium chloride solution (30 mL x 3). The organic phases were collected and dried over anhydrous Na2SO4, filtered, concentrated, and dried with an appropriate amount of silica gel powder. The product was dry-loaded and purified by column chromatography to obtain the pure product. The product was a white solid with a yield of 70%; Mp: 68.4-68.7°C. 1 H NMR (400MHz, CDCl3) δ8.14(s,1H),8.07(d,J=8.4Hz,1H),7.77(dd,J=8.4,1.6Hz,1H),4.58(t,J=6.6Hz,2H),2.99–2.82(m,2H),2.58(s,3H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.83–-102.50(m,1F),-121.86–-122.84(m,1F),-175.22–-176.19(m,1F)ppm. 13 C NMR(101MHz,CDCl3)δ153.72(ddd, 1 J CF =287.1,274.7Hz, 2 J CF =45.8Hz),150.96(s),143.98(s),142.48(s),136.52(s),128.68(s),125.31(ddd, 1 J CF =234.9, 2 J CF=53.7Hz,17.6Hz),124.81(s),122.12(s),73.09(s),25.37(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz),21.84(s)ppm.HRMS(ES+)calcd for C 12 H 10 F3N3NaO2(M+Na) + ,308.0622,found,308.0624.

[0147] Example 3: Preparation of 8-chloro-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A-17

[0148] 3.1 Preparation of 3-chloro-2-amino-N-hydroxybenzamide (I-15)

[0149]

[0150] Sodium hydroxide (80 mmol) was added to a 100 mL round-bottom flask. Water (20 mL) was added and stirred to dissolve. Then, 40 mmol of hydroxylamine hydrochloride was added and stirred for 5 minutes. A solution of methyl 2-amino-3-chlorobenzoate (20 mmol) in methanol (20 mL) was then added to the flask and stirred at room temperature for 10 hours. After the reaction was completed, the methanol in the reaction solution was removed by vortexing, and the pH of the reaction solution was adjusted to 6-7 with 2 mol / L hydrochloric acid. A large amount of solid precipitated, which was filtered, and the filter cake was washed with a small amount of ice water and dried in an infrared oven to obtain the pure product. A white solid with a yield of 33% was obtained. 1 H NMR (400MHz, DMSO-d6) δ11.10(s,1H),9.03(s,1H),7.35(dd,J=10.0,8.0Hz,2H),6.56(t,J=7.8Hz,1H),6.33(s,2H)ppm. 13 C NMR (101MHz, DMSO-d6) δ165.80,144.69,131.54,126.54,118.86,115.40,115.19ppm.

[0151] 3.2 Preparation of 8-chloro-3-hydroxy-benzo[d][1,2,3]triazine-4(3H)-one (I-17)

[0152]

[0153] Disperse the substituted 3-chloro-2-amino-N-hydroxy-5-methylbenzamide (5 mmol) in water (10 mL). Add concentrated hydrochloric acid (2 mL). Add sodium nitrite (10 mmol) in water (10 mL) dropwise while stirring on ice. After the addition is complete, continue the reaction on ice for 1 hour. A solid precipitates, which is filtered, washed with a small amount of ice water, and dried under infrared irradiation to yield the pure product. A white solid is obtained with a yield of 71%. 1 H NMR (400MHz, DMSO-d6) δ13.15 (s, 1H), 8.33–8.08 (m, 2H), 7.85 (t, J = 8.0Hz, 1H) ppm. 13 C NMR (101MHz, DMSO-d6) δ150.18,140.09,135.21,132.89,131.89,123.95,123.20ppm.

[0154] Preparation of 8-chloro-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazin-4(3H)-one (A17)

[0155]

[0156] Sodium hydroxide (4 mmol), 8-chloro-3-hydroxy-benzo[d][1,2,3]triazine-4(3H)-one (2 mmol), 4-bromo-1,1,2-trifluoro-1-butene (6 mmol), and DMF (15 mL) were added to a 50 mL eggplant-shaped flask in sequence and heated to 75°C for overnight reaction. After the reaction was complete, 20 mL of water was added to the flask, and the aqueous phase was extracted three times with ethyl acetate (20 mL x 3). The organic phases were combined and the ethyl acetate was washed three times with saturated sodium chloride solution (30 mL x 3). The organic phases were collected and dried over anhydrous Na2SO4, filtered, concentrated, and an appropriate amount of silica gel powder was added to dryness. The sample was dry-loaded and purified by column chromatography to obtain the pure product. Yellow solid, yield 73%; Mp: 66.6-67.2°C; 1 H NMR (400MHz, CDCl3) δ8.28(dd,J=8.0,1.6Hz,1H),8.0(dd,J=7.6,1.2Hz,1H),7.74(t,J=8.0Hz,1H),4.60(t,J=6.6Hz,2H),3.01–2.84(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.73–-102.44(m,1F),-121.75–-122.61(m,1F),-175.33–-176.12(m,1F)ppm. 13C NMR(101MHz,CDCl3)δ153.74(ddd, 1 J CF =287.3Hz,274.8, 2 J CF =45.7Hz),149.91(s),140.60(s),135.91(s),134.32(s),132.87(s),125.16(ddd, 1 J CF =234.8Hz, 2 J CF =53.7,17.6Hz),124.30(s),123.99(s),73.44(s),25.40(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz)ppm.HRMS(ES+)calcd for C 11 H8 35 ClF3N3O2(M+H) + ,306.0258,found,306.0255.HRMS(ES+)calcd for C 11 H8 37 ClF3N3O2(M+H) + ,308.0228,found,308.0226.

[0157] Example 4: Preparation of 8-methyl-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A5

[0158]

[0159] Compound A5 was prepared using the same procedure as described for compounds A1, A13, and A17 using appropriate starting materials. Pale yellow solid, yield 63%; Mp: 57.3-58.2°C; 1 H NMR (400MHz, CDCl3) δ8.23–8.16(m,1H),7.81–7.74(m,1H),7.68(t,J=8.0Hz,1H),4.59(t,J=6.6Hz,2H),3.00–2.86(m,2H),2.84(s,3H)ppm. 19F NMR (376MHz, CDCl3) δ-101.89–-102.68(m,1F),-121.76–-122.88(m,1F),-175.25–-175.99(m,1F)ppm. 13 C NMR(101MHz,CDCl3)δ153.74(ddd, 1 J CF =287.2,274.7Hz, 2 J CF =45.8Hz),151.11(s),142.51(s),138.77(s),136.20(s),132.43(s),125.30(ddd, 1 J CF =234.9Hz, 2 J CF =53.7,17.6Hz),123.19(s),122.41(s),73.11(s),25.41(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz),17.28(s)ppm.HRMS(ES+)calcd for C 12 H 10 F3N3NaO2(M+Na) + ,308.0622,found,308.0624.

[0160] Example 5: Preparation of 7-methyl-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A4

[0161]

[0162] Using appropriate starting materials, compound A4 was prepared using a similar procedure as described for compounds A1, A13, and A17. White solid, yield 58%; Mp: 74.7-75.4°C; 1 H NMR (400MHz, CDCl3) δ8.24(d,J=8.0Hz,1H),7.96(s,1H),7.62(dd,J=8.0,1.2Hz,1H),4.58(t,J=6.6Hz,2H),3.00–2.82(m,2H),2.60(s,3H)ppm. 19F NMR (376MHz, CDCl3) δ-101.94–-102.59(m,1F),-121.87–-122.84(m,1F),-175.17–-176.16(m,1F)ppm. 13 C NMR(101MHz,CDCl3)δ153.73(ddd, 1 J CF =287.2,274.8Hz, 2 J CF =45.8Hz),150.95(s),146.69(s),144.36(s),134.04(s),128.38(s),125.32(s),125.29(ddd, 1 J CF =234.7Hz, 2 J CF =53.6,17.6Hz),119.82(s),73.14(s),25.39(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz),21.94(s)ppm.HRMS(ES+)calcd for C 12 H 10 F3N3NaO2(M+Na) + ,308.0622,found,308.0624.

[0163] Example 6: Preparation of 7-chloro-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A16

[0164]

[0165] Using appropriate starting materials, a similar procedure as described for compounds A1, A13, and A17 was used to prepare compound A16. Yellow solid, yield 56%; Mp: 77.1-77.3°C; 1 H NMR (400MHz, CDCl3) δ8.31(d,J=8.6Hz,1H),8.17(d,J=2.0Hz,1H),7.76(dd,J=8.6,2.0Hz,1H),4.59(t,J=6.6Hz,2H),3.03–2.77(m,2H)ppm. 19F NMR (376MHz, CDCl3) δ-101.71–-102.40(m,1F),-121.82–-122.71(m,1F),-175.30–-176.18(m,1F)ppm. 13 C NMR(101MHz,CDCl3)δ153.73(ddd, 1 J CF =287.3,274.9Hz, 2 J CF =45.7Hz),150.25(s),144.80(s),141.79(s),133.12(s),128.24(s),127.12(s),125.17(ddd, 1 J CF =234.9Hz, 2 J CF =53.7,17.6Hz),120.62(s),73.37(s),25.38(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz)ppm.HRMS(ES+)calcd for C 11 H7 35 ClF3N3NaO2(M+Na) + ,328.0076,found,328.0079.HRMS(ES+)calcd for C 11 H7 37 ClF3N3NaO2(M+Na) + ,330.0046,found,330.0051.

[0166] Example 7: Preparation of 6-chloro-3-((3,4,4-trifluorobut-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A15

[0167]

[0168] Compound A15 was prepared using the same procedures as described for compounds A1, A13, and A17 using appropriate starting materials. White solid, 55% yield; Mp: 74.0-74.7°C; 1H NMR (400MHz, CDCl3) δ8.32(d,J=2.4Hz,1H),8.14(d,J=8.8Hz,1H),7.90(dd,J=8.8,2.4Hz,1H),4.59(t,J=6.6Hz,2H),2.99–2.84(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.63–-102.50(m,1F),-121.65–-122.78(m,1F),-175.30–-176.20(m,1F)ppm. 13 C NMR(101MHz,CDCl3)δ153.73(ddd, 1 J CF =287.4,274.8Hz, 2 J CF =45.7Hz),149.77(s),142.53(s),139.18(s),135.79(s),130.49(s),125.17(ddd, 1 J CF =234.8Hz, 2 J CF =53.7,17.7Hz),125.00(s),123.43(s),73.34(s),25.38(dd, 2 J CF =22.1Hz, 3 J CF =2.4Hz)ppm.HRMS(ES+)calcd for C 11 H7 35 ClF3N3NaO2(M+Na) + ,328.0076,found,328.0078.HRMS(ES+)calcd for C 11 H7 37 ClF3N3NaO2(M+Na) + ,330.0046,found,330.0049.

[0169] Example 8: Preparation of 3-((3,4,4-trifluorobutyl-3-en-1-yl)oxy)pyrimido[4,5-d][1,2,3]triazine-4(3H)-one, Compound A72

[0170]

[0171] Compound A13 was prepared using the same procedures as described for compounds A1, A13, and A17 using appropriate starting materials. Yellow liquid, 57% yield; 1 H NMR (500MHz, CDCl3) δ9.69 (s, 1H), 9.20 (s, 1H), 4.11 (t, J = 7.1Hz, 2H), 2.88 (t, J = 7.1Hz, 2H) ppm. 19 F NMR (376MHz, CDCl3) δ-101.63–-102.50(m,1F),-121.65–-122.78(m,1F),-175.30–-176.20(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ161.49,161.11,158.37,157.14–152.93(m),152.88,129.58–126.96(m),114.35,68.05,26.83–26.24(m)ppm.HRMS(ES+)calcd for C9H6F3N5O2(M+H) + ,274.0474,found,274.0478.

[0172] Example 9: Preparation of 2,4-dioxo-3-(3,4,4-trifluoro-3-en-1-yl)-1,2,3,4-tetrahydroquinazoline-7-carbonitrile, Compound A74

[0173]

[0174] Compound A74 was prepared using the same procedures as described for compounds A1, A13, and A17 using appropriate starting materials. Yellow oil with a yield of 60%; 1 H NMR (500MHz, CDCl3) δ8.37(d,J=1.5Hz,1H),8.07(d,J=7.4Hz,1H),7.53(dd,J=7.4,1.5Hz,1H),4.27–4.12(m,2H),2.73(t,J=7.1Hz,2H)ppm. 19 FNMR(376MHz, CDCl3)δ-101.55–-102.47(m,1F),-121.68–-122.79(m,1F),-175.26–-176.29(m,1F)ppm. 13C NMR(125MHz, CDCl3)δ161.25,156.86–152.30(m),151.92,142.24,129.49–126.87(m),127 .70,126.55,118.12,117.90,116.15,113.81,39.09,27.48–26.96(m)ppm.HRMS(ES+)calcd for C 13 H8F3N3O2(M+H) + ,296.0569,found,296.0571.

[0175] Example 10: Preparation of 3-((3,4,4-trifluorobutyl-3-en-1-yl)oxy)thiazolo[5,4-d][1,2,3]triazine-4(3H)-one, Compound A73

[0176]

[0177] Compound A73 was prepared using the same procedures as described for compounds A1, A13, and A17 using appropriate starting materials. Yellow liquid, 44% yield; 1 H NMR (500MHz, CDCl3) δ8.77 (s, 1H), 4.11 (t, J = 7.1Hz, 2H), 2.88 (t, J = 7.1Hz, 2H) ppm. 19 F NMR (376MHz, CDCl3) δ-101.65–-102.29(m,1F),-121.80–-122.65(m,1F),-175.38–-176.21(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ157.31–152.49(m),155.39,151.45,150.15,129.76–126.80(m),126.27,68.22,26.58–26.10(m)ppm.HRMS(ES+)calcdfor C8H5F3N4O2S(M+H) + ,279.0085,found,279.0087.

[0178] Example 11: Preparation of 7-(4-chlorophenoxy)-3-(3,4,4-trifluorobutyl-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A50

[0179]

[0180] Compound A50 was prepared using the same procedures as described for compounds A1, A13, and A17 using appropriate starting materials. Yellow-brown liquid, 6% yield; 1 H NMR(500MHz, CDCl3)δ8.21(d,J=7.5Hz,1H),7.43–7.36(m,3H),7.18(dd,J=7.5, 1.5Hz,1H),7.12(d,J=7.6Hz,2H),4.11(t,J=7.1Hz,2H),2.89–2.82(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.51–-102.13(m,1F),-121.68–-122.58(m,1F),-175.44–-176.25(m,1F)ppm. 13 C NMR (125MHz, CDCl3) δ157.54–152.54(m),155.84,155.56,155.38,142.00,129.97,129.96,129.91,129.57 –126.79(m),127.32,119.63,119.61,119.21,119.16,112.22,67.82,25.98–25.34(m)ppm.HRMS(ES+)calcd forC 17 H 11 ClF3N3O3(M+H) + ,398.0441,found,398.0445.

[0181] Example 12: Preparation of 3-(3,4,4-trifluorobutyl-3-en-1-yl)pyrido[3,2-d]pyrimidin-4(3H)-one, Compound A75

[0182]

[0183] Compound A75 was prepared using the same procedures as described for compounds A1, A13, and A17 using appropriate starting materials. Yellow oil; Yield 43%; 1 H NMR(500MHz, CDCl3)δ8.63(dd,J=7.5,1.5Hz,1H),8.09(s,1H),7.84(dd,J=7.5, 1.6Hz,1H),7.58(t,J=7.5Hz,1H),4.38(t,J=7.1Hz,2H),2.75–2.69(m,2H)ppm. 19F NMR (376MHz, CDCl3) δ-101.58–-102.15(m,1F),-121.71–-122.56(m,1F),-175.43–-176.21(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ158.34,157.08–151.07(m),148.25,145.91,144.57,139.50 ,131.76,129.63–126.73(m),125.27,41.88,26.67–25.98(m)ppm.HRMS(ES+)calcd for C 11 H8F3N3O(M+H) + ,256.0619,found,256.0622.

[0184] Example 13: Preparation of 3-isopropyl-6-(3,4,4-trifluorobutyl-3-en-1-yl)pyrido[2,3-d]pyridazin-5(6H)-one, Compound A76

[0185]

[0186] Using appropriate starting materials, a pyridazine ring was obtained according to literature procedures and then reacted with 4-bromo-1,1,2-trifluorobutane-1-ene under basic conditions to produce compound A76. A yellow oil was obtained in 7% yield. 1 H NMR(500MHz, CDCl3) δ8.52(d,J=1.6Hz,1H),8.30(s,1H),8.13(d,J=1.5Hz,1H),4.25 (t,J=7.1Hz,2H),3.27–3.17(m,1H),2.81(t,J=7.1Hz,2H),1.41(d,J=6.9Hz,6H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.52–-102.23(m,1F),-121.68–-122.62(m,1F),-175.40–-176.26(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ163.04,157.13–151.53(m),150.07,143.37,142.43,130.63,129.70–1 26.58(m),123.15,123.09,44.33,29.81,25.08–24.52(m),24.31,24.29ppm.HRMS(ES+)calcd for C 14 H14 F3N3O(M+H) + ,298.1089,found,298.1089.

[0187] Example 14: Preparation of 8-(4-chlorophenyl)-3-(3,4,4-trifluorobutyl-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A25

[0188]

[0189] Using appropriate starting materials, a similar procedure as described for compounds A1, A13, and A17 was used to prepare compound 25. White solid, yield 62%; Mp: 101.0-101.5°C; 1 H NMR (500MHz, CDCl3) δ8.16 (dd, J=7.4, 1.5Hz, 1H), 7.86 (dd, J=7.5, 1.6Hz, 1H), 7.71 (t, J=7.5Hz ,1H),7.56(d,J=7.6Hz,2H),7.34(d,J=7.5Hz,2H),4.11(t,J=7.1Hz,2H),2.89–2.80(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.92–-102.63(m,1F),-121.88–-122.72(m,1F),-175.19–-176.08(m,1F)ppm. 13 C NMR (125MHz, CDCl3) δ157.54–152.58(m),155.86,143.29,136.51,133.89,133.46,130.17,130.16,129.57 ,129.55–126.95(m),129.12,129.11,128.94,125.25,124.10,67.19,26.08–25.25(m)ppm.HRMS(ES+)calcd for C 17 H 11 ClF3N3O2(M+H) + ,382.0492,found,382.0492.

[0190] Example 15: Preparation of 7-(phenylamino)-3-((3,4,4-trifluorobutyl-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A31

[0191]

[0192] Using appropriate starting materials, a similar procedure as described for compounds A1, A13, and A17 was used to prepare compound A31. White solid, yield 65%; Mp: 87.8-89.0°C; 1 H NMR(500MHz, CDCl3)δ8.20(d,J=7.5Hz,1H),7.98–7.94(m,2H),7.38(dd,J=7.5,1.5Hz,1H),7.21(t,J=7.5Hz ,2H),7.05(dd,J=7.6,1.5Hz,2H),6.85(tt,J=7.5,1.5Hz,1H),4.11(t,J=7.1Hz,2H),2.88–2.82(m,2H)ppm. 19 FNMR(376MHz, CDCl3)δ-101.98–-102.59(m,1F),-121.98–-122.84(m,1F),-175.17–-176.06(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ155.38,155.16(tdd,J=251.8,20.0,4.6Hz),144.48,142.97,141.11,129.55–126.96(m),129 .33,129.32,127.46,121.58,121.21,116.35,116.29,116.09,111.51,67.19,25.99–25.49(m)ppm.HRMS(ES+)calcd for C 17 H 13 F3N4O2(M+H) + ,363.0991,found,363.0993.

[0193] Example 16: Preparation of 6-(thiophene-2-carbonyl)-3-(3,4,4-trifluorobutyl-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A60

[0194]

[0195] Using appropriate starting materials, a similar procedure as described for compounds A1, A13, and A17 was used to prepare compound A60. Yellow solid, yield 61%; Mp: 68.8-69.3°C; 1H NMR(500MHz, CDCl3)δ8.37(d,J=1.5Hz,1H),8.09–8.03(m,2H),7.92(dd,J=7.5,1.5Hz,1H),7. 73(dd,J=7.5,1.6Hz,1H),7.21(t,J=7.5Hz,1H),4.11(t,J=7.1Hz,2H),2.88–2.83(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.83–-102.60(m,1F),-121.83–-122.92(m,1F),-175.13–-176.18(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ189.53,155.91,155.16(tdd,J=251.8,20.0,4.6Hz),145.62,142.45,135.01,134.55,133 .69,133.30,129.55–126.96(m),128.25,128.22,127.60,121.01,67.19,25.98–25.51(m)ppm.HRMS(ES+)calcd for C 16 H 10 F3N3O3S(M+H) + ,382.0395,found,382.0398.

[0196] Example 17: Preparation of 7-morpholin-3-((3,4,4-trifluorobutyl-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A39

[0197]

[0198] Using appropriate starting materials, similar procedures as described for compounds A1, A13, and A17 were used, followed by coupling reactions to obtain compound A39. Yellow oil; Yield 62%; 1 H NMR (500MHz, CDCl3) δ8.14(d,J=7.4Hz,1H),7.78(d,J=1.4Hz,1H),7.10(dd,J=7.5,1.5Hz,1H),4.11(t, J=7.1Hz,2H),3.80(t,J=7.1Hz,4H),3.30(t,J=7.1Hz,2H),3.25(t,J=7.1Hz,2H),2.88–2.83(m,2H)ppm. 19F NMR (376MHz, CDCl3) δ-101.83–-102.60(m,1F),-121.83–-122.92(m,1F),-175.13–-176.18(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ155.46,155.16(tdd,J=251.8,20.0,4.6Hz),149.94,142.10,129.66–126.86(m),1 27.24,118.75,113.28,106.81,67.17,66.69,66.67,48.35,48.33,26.00–25.49(m)ppm.HRMS(ES+)calcd for C 15 H 15 F3N4O3(M+H) + ,357.1096,found,357.1099.

[0199] Example 18: Preparation of 5-((4-chlorobenzyl)oxy)-3-((3,4,4-trifluorobutyl-3-en-1-yl)oxy)benzo[d][1,2,3]triazine-4(3H)-one, Compound A34

[0200]

[0201] Using appropriate starting materials, a similar procedure as described for compounds A1, A13, and A17 was followed by aromatic nucleophilic substitution to give compound A34. Yellow solid, 7% yield; Mp: 85.9-87.6°C; 1 HNMR(500MHz, CDCl3)δ7.92(dd,J=7.5,1.5Hz,1H),7.54(t,J=7.5Hz,1H),7.45–7.38(m,4H) ,7.24(dd,J=7.5,1.5Hz,1H),5.03(s,2H),4.09(t,J=7.1Hz,2H),2.86(t,J=7.1Hz,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.83–-102.60(m,1F),-121.83–-122.92(m,1F),-175.13–-176.18(m,1F)ppm. 13C NMR (125MHz, CDCl3) δ158.07, 157.49, 154.96 (tdd, J = 251.8, 19.8, 4.5Hz), 143.18, 135.33, 134.91, 133.03, 12 9.55–126.92(m),129.12,128.78,119.91,113.20,112.53,70.64,68.05,25.98–25.32(m)ppm.HRMS(ES+)calcd for C 18 H 13 ClF3N3O3(M+H) + ,412.0598,found,412.0595.

[0202] Example 19: Preparation of n-(4-oxo-3-((3,4,4-trifluorobutane-3-en-1-yl)oxy)-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)benzamide, Compound A10

[0203]

[0204] Compound A38 was prepared using appropriate starting materials using a similar procedure as described for compounds A1, A13, and A17, followed by amination and acid-amine condensation. A yellow liquid was obtained in 42% yield. 1 H NMR(500MHz, CDCl3)δ8.73(d,J=1.5Hz,1H),8.20(d,J=7.5Hz,1H),7.98–7.94(m,2H),7.6 5(dd,J=7.5,1.5Hz,1H),7.56–7.47(m,3H),4.11(t,J=7.1Hz,2H),2.91–2.74(m,2H)ppm. 19 F NMR(376MHz, CDCl3)δ-63.00(s,3F),-101.65–-102.29(m,1F),-121.80–-122.65(m,1F),-175.38–-176.21(m,1F)ppm. 13 CNMR(125MHz, CDCl3)δ167.64,156.01,157.92–151.80(m),143.20,139.28,134.04,131.86,129.62–126.76(m) ,128.51,128.51,128.16,128.10,127.37,121.58,119.61,113.88,67.82,25.92–25.42(m)ppm.HRMS(ES+)calcd for C18 H 13 F3N4O3(M+H) + ,391.0940,found,391.0943.

[0205] Example 20: Preparation of 4-(4-chlorophenyl)-1-(3,4,4-trifluorobutyl-3-en-1-yl)piperidin-2-one, Compound A80

[0206] Preparation of 4-(4-chlorophenyl)piperidin-2-one,

[0207]

[0208] The entire reaction was carried out under argon. In an eggplant-shaped flask, 21.6 mg of Rh(acac)(C2H4), 5.6 mg of (R)-binap, and 122 mg of 4-chlorophenylboroxine were added. Then, 1 mL of 1,4-dioxane was added and the mixture was stirred at room temperature for 3 minutes. 37.4 mg of 5,6-dihydro-2(1H)-pyridone and 18 μL of water were added and stirred at 40°C for 12 hours. After evaporation of the solvent, the residue was dissolved in ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated sodium bicarbonate, and dried over anhydrous magnesium sulfate. The title compound was purified by column chromatography. 1 H NMR(CDCl3)δ1.86-1.97(m,1H),2.04-2.11(m,1H),2.45(dd,J=17.6,11.0Hz,1H),2.67(dd d,J=17.6,5.3,1.7Hz,1H),3.09(tdd,J=11.0,5.3,3.2Hz,1H),3.38-3.45(m,2H),6.58(br s,1H),7.16(d,J=8.4Hz,2H),7.32(d,J=8.4Hz,2H);

[0209] Preparation of 4-(4-chlorophenyl)-1-(3,4,4-trifluorobutyl-3-en-1-yl)piperidin-2-one

[0210]

[0211] To a 50 ml eggplant-shaped flask, add 40 mg of 4-(4-chlorophenyl)piperidin-2-one and 5 ml of anhydrous tetrahydrofuran. Add 11 mg of 60% sodium hydride under ice-cooling conditions, then add 36 mg of 4-bromo-1,1,2-trifluorobutane-1-ene. Raise the temperature to 50°C for reaction. When TLC indicates the reaction is complete, quench the reaction by adding water. Extract the aqueous phase three times with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, and purify by column chromatography to obtain the title compound as a white solid in a 55% yield.1 H NMR(CDCl3)δ1.86-1.97(m,1H),2.04-2.11(m,1H),2.45(dd,J=17.6,11.0Hz,1H),2.67(ddd,J=17.6,5.3,1.7Hz,1H),3.00–2.83(m,2 19F NMR(376MHz, CDCl3)δ-101.90–-102.58(m,1F),-121.89–-122.78(m,1F),-175.27–-176.08(m,1F)ppm.13C NMR (CDCl3) δ25.40 (dd, 2JCF = 22.1Hz, 3JCF = 2.4Hz), 29.46, 37.87, 38.65, 41.26, 125.26 (ddd, 1JCF = 234.7Hz, 2JCF = 53.7, 17 .6Hz),127.93,128.92,132.59,141.94,153.74(ddd,1JCF=287.2,274.8Hz,2JCF=45.8Hz),171.67ppm.HRMS(ES+)calcdfor C15H15ClF3NO(M+H)+,317.0794,found,317.0799.

[0212] Example 21. Preparation of 7-chloro-2-phenyl-3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)quinazolin-4(3H)-one, Compound B43

[0213]

[0214] Using appropriate starting materials and a similar procedure as described for compound B1, compound A43 was prepared as a white solid with a yield of 55%; Mp: 73.0-75.7°C; 1 H NMR(500MHz, CDCl3)δ8.27(d,J=7.5Hz,1H),7.77–7.72(m,2H),7.65(d,J=1.5Hz,1H), 7.49–7.42(m,4H),6.96(t,J=6.9Hz,1H),3.17(q,J=7.0Hz,2H),2.64–2.59(m,2H)ppm. 19F NMR (376MHz, CDCl3) δ-101.63–-102.50(m,1F),-121.65–-122.78(m,1F),-175.30–-176.20(m,1F)ppm. 13 C NMR (125MHz, CDCl3) δ160.56,157.37–151.76(m),153.78,146.39,137.03,132.46,130.82,129.45,129.44 –126.97(m),129.23,129.17,128.17,127.22,122.98,120.15,44.33,25.01–24.06(m)ppm.HRMS(ES+)calcd for C 18 H 13 ClF3N3O(M+H) + ,380.0699,found,380.0697.

[0215] Example 22: Preparation of 3-((3,4,4-trifluorobutyl-3-en-1-yl)amino)pyrido[4,3-d]pyrimidin-4(3H)-one, Compound B47

[0216]

[0217] Using appropriate starting materials, a similar procedure as described for compound B1 was used to prepare compound A2. White solid, yield 57%; Mp: 73.7-74.4 °C; 1 H NMR(500MHz, CDCl3)δ9.40(s,1H),9.24(t,J=6.8Hz,1H),8.54(d,J=7.5Hz,1H), 8.02(s,1H),7.33(d,J=7.5Hz,1H),3.11(q,J=6.9Hz,2H),2.64–2.58(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.94–-102.59(m,1F),-121.87–-122.84(m,1F),-175.17–-176.16(m,1F)ppm. 13 C NMR(125MHz, CDCl3)δ159.21,157.12–152.00(m),152.42,147.23,146.97,143.74 ,129.75–126.65(m),120.23,114.14,43.82,25.72–24.94(m)ppm.HRMS(ES+)calcd for C11 H9F3N4O(M+H) + ,271.0728,found,271.0725.

[0218] Example 23: Preparation of 3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)-2-(trifluoromethyl)quinazolin-4(3H)-one, Compound B1

[0219] 23.1 Preparation of 2-(trifluoromethyl)-4H-benzo[d][1,3]oxazin-4-one, Compound 7.

[0220]

[0221] In a 50 ml eggplant-shaped flask, add 500 mg of anthranilic acid and 6 ml of trifluoroacetic anhydride. Reflux for 4 hours. Once the reaction is complete, remove the solvent under reduced pressure to obtain the crude product. Use it directly in the next step without purification. A white solid, yield: 70%. 1 H NMR (400MHz, DMSO-d6) δ7.61 (d, J = 8.7 Hz, 2H), 6.54 (d, J = 8.6 Hz, 2H).

[0222] 23.2 Preparation of 3-amino-2-(trifluoromethyl)quinazolin-4(3H)-one, ie, compound 8.

[0223]

[0224] In a 50ml eggplant-shaped flask, add 300mg of 2-(trifluoromethyl)-4H-benzo[d][1,3]oxazin-4-one, followed by 5ml of ethanol and then 0.06ml of hydrazine hydrate dropwise. Reflux and react until TLC indicates completion. Cool to room temperature, concentrate in vacuo, add 20ml of water, extract the aqueous phase three times with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, and purify by column chromatography to obtain the desired product. A white solid, yield: 60%; mp: 146–148°C. 1 H NMR (400MHz, DMSO-d6) δ7.65–7.60(m,2H),6.57–6.53(m,2H).

[0225] 23.3 Preparation of 3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)-2-(trifluoromethyl)quinazolin-4(3H)-one, Compound B1.

[0226]

[0227] To a 50ml eggplant-shaped flask, add 230mg of 3-amino-2-(trifluoromethyl)quinazolin-4(3H)-one, followed by 15ml of acetonitrile, 207mg of anhydrous potassium carbonate, and 190mg of 4-bromo-1,1,2-trifluorobutane-1-ene. React at 70°C. TLC results in completion of the reaction. Concentrate under reduced pressure and purify by column chromatography to obtain the desired product as a yellow oil. Yield: 50%. 1 H NMR (400MHz, CDCl3) δ7.85–7.78(m,2H),6.65–6.59(m,2H),4.40(t,J=6.3Hz,2H),2.76–2.66(m,2H). 19 F NMR(376MHz, CDCl3)δ-73.73,-103.38(ddt,J=85.2,32.8,2.7Hz),-123.53–-124.19(m),-174.61–-175.49(m). 13 C NMR (125MHz, CDCl3) δ162.19, 154.75 (tdd, J=251.8, 19.9, 4.6Hz), 147.46 (q, J=32.0Hz), 145.17, 135.12, 128.31 (dtt, J=252.5,20.4,4.8Hz),127.00,126.59,126.36,123.75–117.04(m),119.84,44.06,25.13–24.43(m).HRMS(ES+)calcd for C 13 H9F6N3O(M+H) + ,338.0650,found,338.0652.

[0228] Example 24: Preparation of 8-chloro-3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)-2-(trifluoromethyl)quinazolin-4(3H)-one, Compound B2

[0229]

[0230] Compound B2 was prepared using the same procedure as described for compounds 7, 8, and B1 using appropriate starting materials. Yellow oil, yield: 53%; 1H NMR (400MHz, CDCl3) δ8.15 (dd, J=7.5, 1.5Hz, 1H), 7.69 (dd, J=7.5, 1.6Hz, 1H), 7.53 (t, J=7.5Hz,1H),7.08(t,J=6.1Hz,1H),3.12(td,J=7.0,6.1Hz,2H),2.60(t,J=7.1Hz,2H). 19 F NMR(376MHz, CDCl3)δ-73.73,-103.38(ddt,J=85.2,32.8,2.7Hz),-123.53–-124.19(m),-174.61–-175.49(m). 13 C NMR (125MHz, CDCl3) δ161.25,154.83(tdd,J=251.9,20.0,4.6Hz),144.47(q,J=32.0Hz),143.57,134.89,128.31(dtt,J =252.1,20.0,4.6Hz),127.88,127.76,126.12,120.96,120.08(q,J=268.0Hz),43.94,25.77–23.49(m).HRMS(ES+)calcd for C 13 H8ClF6N3O(M+H) + ,372.0260,found,372.0263.

[0231] Example 25: Preparation of 7-chloro-3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)-2-(trifluoromethyl)quinazolin-4(3H)-one, Compound B3

[0232]

[0233] Using appropriate starting materials, compound B3 was prepared using a similar procedure as described for compounds 7, 8, and B1. Yellow oil, yield: 52%; 1 H NMR (500MHz, CDCl3) δ8.23(d,J=7.5Hz,1H),7.57(d,J=1.5Hz,1H),7.43(dd,J=7.5,1 .5Hz,1H),7.37(t,J=6.1Hz,1H),3.12(td,J=7.1,6.1Hz,2H),2.60(t,J=7.1Hz,2H). 19F NMR(376MHz, CDCl3)δ-73.63,-102.38(ddt,J=85.2,32.8,2.7Hz),-123.53–-124.19(m),-174.61–-175.49(m). 13 CNMR(125MHz, CDCl3)δ161.83,154.83(tdd,J=251.9,20.0,4.6Hz),146.53(q,J=32.0Hz),145.39,136.80,129.55–127 .07(m),128.05,127.26,123.84–116.64(m),123.54,120.84,43.97,24.61(dtd,J=28.0,4.9,2.2Hz).HRMS(ES+)calcd for C 13 H8ClF6N3O(M+H) + ,372.0261,found,372.0264.

[0234] Example 26: Preparation of 7-methyl-3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)-2-(trifluoromethyl)quinazolin-4(3H)-one, Compound B7

[0235]

[0236] Compound B7 was prepared using the same procedure as described for compounds 7, 8, and B1 using appropriate starting materials. Yellow oil, yield: 51%; 1 H NMR(500MHz, CDCl3) δ8.19(d,J=7.5Hz,1H),7.54(dd,J=1.5,0.7Hz,1H),7.39(t,J=6.1Hz,1H),7 .23(ddd,J=7.9,2.0,0.8Hz,1H),3.12(td,J=7.1,6.2Hz,2H),2.60(t,J=7.1Hz,2H),2.39(m,3H). 19 F NMR(376MHz, CDCl3)δ-73.63,-102.38(ddt,J=85.2,32.8,2.7Hz),-123.53–-124.19(m),-174.61–-175.49(m). 13C NMR(125MHz, CDCl3)δ162.27,154.83(tdd,J=251.9,20.0,4.6Hz),146.83(q,J=32.0Hz),144.47,139.39,129.68–127.00(m ),127.84,127.44,124.80,121.18,120.64(q,J=268.0Hz),43.97,24.61(dtd,J=28.0,4.9,2.3Hz),20.73.HRMS(ES+)calcd for C 14 H 11 F6N3O(M+H) + ,352.0806,found,352.0809.

[0237] Example 27: Preparation of 7-methoxy-3-((3,4,4-trifluoromethyl-3-en-1-yl)amino)-2-(trifluoromethyl)quinazolin-4(3H)-one, Compound B11

[0238]

[0239] Using appropriate starting materials, compound B11 was prepared using a similar procedure as described for compounds 7, 8, and B1. Yellow oil, yield: 45%; 1 H NMR (500MHz, CDCl3) δ8.07 (d, J=7.5Hz, 1H), 6.99 (dd, J=7.5, 1.5Hz, 1H), 6.88 (d ,J=1.5Hz,1H),3.81(s,3H),3.12(td,J=7.1,6.2Hz,2H),2.60(t,J=7.1Hz,2H). 19 F NMR(376MHz, CDCl3)δ-73.63,-102.38(ddt,J=85.2,32.8,2.7Hz),-123.53–-124.19(m),-174.61–-175.49(m). 13C NMR (125MHz, CDCl3) δ162.07, 161.82, 154.83 (tdd, J=251.9, 20.0, 4.6Hz), 146.74 (q, J=32.1Hz), 144.11, 128.31 (dtt, J=252.1, 20. 0,4.8Hz),127.62,120.40(q,J=268.1Hz),119.35,113.48,107.17,55.63,43.97,24.61(dtd,J=27.9,4.8,2.2Hz).HRMS(ES+)calcd for C 14 H 11 F6N3O2(M+H) + ,368.0755,found,368.0779.

[0240] Example 28: Preparation of 2-methyl-4-oxo-3-(3,4,4-trifluoro-3-en-1-yl)amino)-3,4-dihydroquinazoline-7-carbonitrile, Compound B36

[0241]

[0242] Using appropriate starting materials, compound B36 was prepared using a similar procedure as described for compounds 7, 8, and B1. Yellow oil, yield: 48%; 1 H NMR (500MHz, CDCl3) δ8.17(d,J=7.5Hz,1H),7.95(d,J=1.5Hz,1H),7.82(dd,J=7.5,1.5Hz,1H),3.15–3.08(m,2H),2.68(s,3H),2.66(t,J=7.1Hz,2H). 19 F NMR(376MHz, CDCl3)δ-73.63,-102.38(ddt,J=85.2,32.8,2.7Hz),-123.53–-124.19(m),-174.61–-175.49(m). 13 C NMR (125MHz, CDCl3) δ162.54,156.84–152.45(m),152.70,145.25,131.73,129.55–127.07(m) ),127.33,122.72,121.72,118.32,115.81,44.49,25.37–24.85(m),20.80.HRMS(ES+)calcd for C 14 H 11 F3N4O(M+H) +,363.0602,found,363.0604.

[0243] Example 29: Preparation of 3-((3,4,4-trifluorobutyl-3-en-1-yl)amino)pyrido[4,3-d]pyrimidin-4(3H)-one, Compound B47

[0244]

[0245] Using appropriate starting materials, compound B47 was prepared using a similar procedure as described for compounds 7, 8, and B1. Yellow oil; Yield: 38%; 1 H NMR(500MHz, CDCl3)δ9.40(s,1H),9.24(t,J=6.8Hz,1H),8.54(d,J=7.5Hz,1H), 8.02(s,1H),7.33(d,J=7.5Hz,1H),3.11(q,J=6.9Hz,2H),2.64–2.59(m,2H)ppm. 19 F NMR(472MHz, CDCl3)δ-62.56,-65.74,-96.92,-100.16. 13 C NMR(125MHz, CDCl3)δ159.23,156.99–152.55(m),152.42,147.21,147.04,143.78 ,129.64–126.71(m),120.23,114.14,43.80,25.76–24.85(m)ppm.HRMS(ES+)calcd for C 11 H9F3N4O(M+H) + ,271.0728,found,271.0726.

[0246] Example 30: Preparation of 4-oxo-3-((3,4,4-trifluorobutyl-3-en-1-yl)amino)-3,4-dihydrothieno[2,3-d]pyrimidine-2-carbonitrile, Compound B48

[0247]

[0248] Using appropriate starting materials, compound B48 was prepared using a similar procedure as described for compounds 7, 8, and B1. Yellow oil, yield: 39%; 1H NMR (500MHz, CDCl3) δ7.57(d,J=7.5Hz,1H),7.50(d,J=7.5Hz,1H),6.76(t,J=6.0Hz,1H),3.16(td,J=7.1,6.0Hz,2H),2.63–2.57(m,2H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.90–-102.58(m,1F),-121.89–-122.78(m,1F),-175.27–-176.08(m,1F)ppm. 13 C NMR (125MHz, CDCl3) δ159.85,157.39–152.07(m),153.93,134.58,129.61–127.00(m ),124.11,119.83,115.51,111.54,44.06,25.37–23.88(m)ppm.HRMS(ES+)calcdfor C11H7F3N4OS(M+H) + ,301.0293,found,301.0295.

[0249] Example 31: Preparation of 2-((4-chlorophenyl)amino)-6-methyl-3-((3,4,4-trifluorobutyl-3-en-1-yl)amino)quinazolin-4(3H)-one, Compound B49

[0250]

[0251] Compound B25 was prepared using the same procedure as described for compounds 7, 8, and B1 using appropriate starting materials. Yellow oil, yield: 44%; 1 H NMR (500MHz, CDCl3) δ7.84–7.81(m,1H),7.64–7.60(m,2H),7.49–7.43(m,2H),7.33–7.29 (m,2H),6.93(t,J=6.7Hz,1H),3.12(q,J=7.0Hz,2H),2.66–2.61(m,2H),2.37(s,3H)ppm. 19 F NMR (376MHz, CDCl3) δ-101.80–-102.58(m,1F),-121.89–-122.78(m,1F),-175.27–-176.08(m,1F)ppm. 13CNMR(125MHz, CDCl3)δ157.29–151.61(m),149.67,142.05,139.73,132.95,132.39,129.71–126.75(m),129.15 ,129.15,128.77,125.32,124.96,122.58,122.57,118.34,44.14,25.15–24.31(m),20.73ppm.HRMS(ES+)calcd for C 19 H 16 ClF3N4O(M+H) + ,409.0965,found,409.0967.

[0252] Example 32: Nematicidal Activity Test of the Compounds of the Invention

[0253] Root-knot nematodes belong to the phylum Nematoda, order Tylenchida, suborder Tylenchida, superfamily Heteroderidea, subfamily Meloidogyninae, and genus Meloidogyne. They are a plant parasitic nematode that causes serious damage.

[0254] The southern root-knot nematode (Meloidogyne incognita) was used as the test object and cucumber seedlings as the test host, and the test was carried out using the test tube planting method.

[0255] Procedure: In vitro testing: Prepare the test sample at the desired concentration and prepare a sufficient number of second-instar root-knot nematode larvae. Then, perform the test in a 96-well plate, repeating each concentration and sample in duplicate. Record the total number and mortality of second-instar root-knot nematodes in the 96-well plate. Observe the number of dead nematodes under a microscope every 24 hours to calculate the mortality rate. In vivo testing: Plant cucumber seedlings in test tubes, add the appropriate amount of the prepared solution, and seed each tube with approximately 2,000 larvae. Incubate the tubes at 20-25°C under 10-hour light conditions. After 7 days, count the number of root knots on each plant's root system. Repeat the test three times for each sample, with four replicates per test.

[0256] Distilled water was used as blank control, distilled water plus root-knot nematodes was used as negative control, and fenamiphos, avermectin solution, and flumethalin were used as positive controls.

[0257] Refer to Table 1 for calculation of disease index grading for in vivo testing.

[0258] Table 1. In vivo disease index grading table

[0259] Root knot inhibition rate Activity level 80％-100％ A 60％-80％ B 40％-60％ C 20％-40％ D 10％-20％ E

[0260] Table 2 lists the formula (I) In vivo nematicidal activities of some of the compounds shown.

[0261] Table 2: In vivo activity data of some compounds in formula (I)

[0262]

[0263]

[0264]

[0265]

[0266]

[0267]

[0268]

[0269]

[0270]

[0271]

[0272]

[0273]

[0274]

[0275]

[0276]

[0277]

[0278]

[0279] The calculation of compound in vitro activity is shown in Table 3.

[0280] Table 3 lists the formula (I) In vitro nematicidal activities of some of the compounds shown.

[0281] Table 3: In vitro activity data of some compounds in formula (I)

[0282]

[0283]

[0284]

[0285]

[0286]

[0287]

[0288]

[0289]

[0290]

[0291]

[0292]

[0293]

[0294]

[0295]

[0296]

[0297] As can be seen from the above table, the compounds of the present invention have very good nematicidal activity and can exhibit significant nematicidal effects at a concentration as low as 40 ppm.

[0298] All documents mentioned in this application are incorporated herein by reference, just as if each document were incorporated herein by reference individually. It should also be understood that after reading the above teachings of the present invention, those skilled in the art may make various changes or modifications to the present invention, and that such equivalents also fall within the scope of the claims appended hereto.

Claims

1. A compound represented by formula (I-1) or (I-2) or a pesticide-acceptable salt thereof: Where, G is independently one or more groups selected from the group consisting of H, halogen, nitro, cyano, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkyl, C 1-6 Haloalkyl, substituted or unsubstituted C 3-10 Cycloalkyl, substituted or unsubstituted C 1-6 Silyl, substituted or unsubstituted C 1-6 Alkylthio, substituted or unsubstituted C 2-6 Alkenyl, substituted or unsubstituted C 2-6 Alkynyl, substituted or unsubstituted amino, substituted or unsubstituted C 5-10 Aryl, substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 5-10 heteroaryl, substituted or unsubstituted aldehyde, substituted or unsubstituted amide, substituted or unsubstituted sulfonate, substituted or unsubstituted C 2-6 Ester group; or, two or more G and the carbon atom to which they are attached together constitute a substituted or unsubstituted C 3-6 Carbocyclic, or substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 3-6 carbon heterocycles; Z is independently selected from: hydrogen, substituted or unsubstituted C 1-6 Alkyl, C 1-6 Haloalkyl, cyano, substituted or unsubstituted amino, substituted or unsubstituted C 5-10 Aromatic ring, substituted or unsubstituted C containing 1-3 heteroatoms independently selected from O, N or S 5-10 aromatic heterocycles; The "substituted" is substituted by a substituent selected from the group consisting of halogen, cyano, nitro, C 1-6 Alkyl, C 1-6 Halogenated alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, formyl.

2. The compound according to claim 1 or a pesticidally acceptable salt thereof, wherein G is independent and is 1-3.

3. The compound according to claim 2 or a pesticidally acceptable salt thereof, wherein G is independent and is 1-2.

4. The compound according to claim 1 or a pesticidally acceptable salt thereof, wherein The C 1-6 Haloalkyl is trifluoromethyl.

5. A compound selected from the group consisting of:

6. The compound according to claim 1 or a pesticidally acceptable salt thereof, wherein The compound is shown in the following formula: In the formula, G is independently one or more groups selected from the group consisting of H, halogen, nitro, substituted or unsubstituted C 1-6 Alkoxy, substituted or unsubstituted C 1-6 Alkyl, C 1-6 Halogenated alkyl.

7. The compound according to claim 6 or a pesticidally acceptable salt thereof, wherein G is independent and is 1-3.

8. The compound according to claim 7 or a pesticidally acceptable salt thereof, wherein G is independent and is 1-2.

9. The compound according to claim 6 or a pesticidally acceptable salt thereof, wherein the compound is selected from:

10. The compound according to claim 9 or a pesticidally acceptable salt thereof, wherein The compound is Compound A16.

11. An agricultural composition, characterized in that The invention comprises: 0.001-99.00 wt % of the compound according to any one of claims 1 to 10, the pesticide-acceptable salt of the compound, or a combination thereof, and a pesticide-acceptable carrier and / or excipient.

12. Use of the compound according to any one of claims 1 to 10, the pesticidally acceptable salt of the compound, or the agricultural composition according to claim 11 for killing or preventing nematodes in crop fields or for preparing a nematicide for killing or preventing nematodes.

13. A method for killing or preventing nematodes in a crop field, the method comprising applying an effective amount of the compound according to any one of claims 1 to 10, the pesticidally acceptable salt of the compound, or the agricultural composition according to claim 11 to an area where nematodes need to be killed or prevented.

14. The method according to claim 13, wherein The nematodes are selected from the group consisting of: root-knot nematodes; cyst nematodes; heterodermal nematodes; tumor nematodes; stem and leaf bud nematodes; thorn nematodes; pine nematodes; ring nematodes; bulb nematodes; cone nematodes; spiral nematodes; sheath nematodes; crown nematodes; pseudo-root-knot nematodes; needle nematodes; nail nematodes; root-rot nematodes; piercing nematodes; kidney-shaped nematodes; stump root nematodes; dwarf nematodes; citrus nematodes; and sword nematodes.

15. The method according to claim 14, wherein The root-knot nematode is Meloidogyne arenaria, Meloidogyne chitwoodi, Meloidogyne exigua, Meloidogyne hapla, Meloidogyne incognita, or Meloidogyne javanica; The cyst nematode is Globodera rostochiensis, Globodera pallida or Globodera tabacum; The Heterodera nematode is a cereal cyst nematode (Heterodera avenae), a soybean cyst nematode (Heterodera raglycines), a beet cyst nematode (Heterodera schachtii) or a clover cyst nematode (Heterodera trifolii); The tumor nematode is Anguina funesta or Anguina tritici; The stem and leaf bud nematodes are Aphelenchoides besseyi, Aphelenchoides fragariae or Aphelenchoides ritzemabosi; The stinging nematode is the weed stinging nematode (Belonolaimus longicaudatus); The pine nematode is pine wood nematode (Bursaphelenchus xylophilus); The ring nematode is of the genus Criconema, Criconemella, Criconemoides or Mesocriconema; The bulb nematode is Ditylenchus destructor, Ditylenchus dipsaci or Ditylenchus myceliophagus; The trypanosome is of the genus Dolichodorus; The spiral nematode is Helicotylenchus dihystera or Helicotylenchus multicintus; The sheath nematode is of the genus Hemicycliophora or Hemicriconemoides; The crown nematode is Hoploaimus columbus; The pseudorhizobium nematode is Nacobbus aberrans; The needle nematode is Longidorus elongatus; The nail nematode is of the genus Paratylenchus; The root rot nematode is Pratylenchus brachyurus, Pratylenchus coffee, Pratylenchus zeae or Pratylenchus penetrans; The nematode is Radopholus similis; The reniform nematode is Rotylenchus robustus; The stump root nematode is Trichodorus primitivus; The dwarf nematode is Tylenchorhynchus claytoni or Tylenchorhynchus dubius; The citrus nematode is Tylenchulus semipenetrans; The Xiphinema is Xiphinema americanum, Xiphinema index or Xiphinema diversicaudatum.

16. The method according to claim 15, wherein The nematode is the southern root-knot nematode (Meloidogyne incognita).

Images