Pyrimidine compounds for the control of invertebrate pests

Abstract

This invention relates to formula I [Case 1] The present invention relates to the compound TIFF2026516766000021.tif30170 (wherein the formula, the variables have the meanings defined herein), compositions comprising the same, combinations of active compounds comprising the same, and their use for protecting growing plants and animals from attack or parasitism by invertebrate pests, as well as seeds comprising such compounds.

Description

Technical Field

[0001] The present invention relates to formula I

Chem.

[0002] The present invention also provides agricultural compositions comprising at least one compound of formula I, its stereoisomers and / or an agrochemically acceptable salt thereof, and at least one liquid and / or solid carrier, in particular at least one inert liquid and / or solid agrochemically acceptable carrier.

[0003] The present invention also provides a veterinary composition comprising at least one compound of formula I, its stereoisomers and / or veterinarily acceptable salt thereof, and at least one liquid and / or solid carrier, in particular at least one inert veterinary liquid and / or solid acceptable carrier.

[0004] The present invention also provides a method for controlling invertebrate pests, the method comprising treating a pest, its food source, its habitat or breeding ground, or cultivated plants, plant propagation materials (such as seeds), soil, area, material or environment, or material, cultivated plants, plant propagation materials (such as seeds), soil, surface or space that is intended to be defended against attack or parasitism by the pest, with an effective amount of a compound of formula I as defined herein or a salt thereof.

[0005] The present invention also relates to plant propagation materials, particularly seeds, comprising at least one compound of formula I and / or an agrochemically acceptable salt thereof.

[0006] The present invention further relates to a method for treating or defending an animal against parasitic infestation or infection, the method comprising contacting the animal with an effective amount of a compound of formula I or a veterinarily acceptable salt thereof that is effective in killing parasites. Contacting an animal with compound I, a salt thereof or a veterinary composition of the present invention means applying or administering it to the animal.

[0007] International Publication Nos. 2017 / 192385, 2019 / 170626, 2019 / 197468, 2021 / 165195, 2021 / 224323, 2023 / 037249, and 2023 / 058748 describe structurally closely related active compounds, where 4-pyrimidine is generally substituted at the 6-position with a group typically selected from CN, amide, CF3, and sulfoximine. These compounds are said to be useful for controlling invertebrate pests.

[0008] Nevertheless, there is still a need for highly effective and versatile agents for controlling invertebrate pests. Therefore, the object of the present invention is to provide a compound that has good pesticidal activity and exhibits a broad activity spectrum against a large number of different invertebrate pests, particularly insects and other pests that are difficult to control.

[0009] It has been found that these objectives can be achieved by the compounds of formula I as shown and defined below, as well as their stereoisomers, salts, tautomers, and N-oxides, particularly their agrochemically acceptable salts. [Modes for carrying out the invention]

[0010] Compound I is R 1 Corresponding precursor compound I having =H, and a suitable reagent R 1 -Y (wherein Y is a nucleophilic leaving group such as a halogen, tosylate, or mesylate, preferably Br or Cl) can be prepared by reaction. This reaction can be carried out under generally known conditions. [ka]

[0011] This conversion is typically carried out in an inert solvent, in the presence of a base, at a temperature of -10°C to +110°C, preferably 0°C to 25°C [see International Publication No. 2002100846].

[0012] The starting materials generally react with each other in equimolar amounts. With respect to yield, it may be advantageous to use an excess of III based on II, as described in International Publication No. 2023 / 025617.

[0013] Alternatively, compound I can be prepared from intermediate IV and hydrazine V, as described in International Publication No. 2021 / 224323: [ka]

[0014] Compound IV is known from International Publication Nos. 2017 / 192385 and 2019 / 206799. 4 Compound V having the following characteristics: dihalopyrimidine Va (wherein X is a halogen, preferably Cl), and reagent R 4 -X' (wherein X' is a halogen, such as I, Br, Cl, or F, preferably Br) can be prepared in two steps: [ka]

[0015] The first step is a cross-coupling reaction, as known from, for example, International Publication No. 2019 / 072143 and International Publication No. 2015 / 008073. The resulting intermediate Vb can be converted to compound V by reaction with hydrazine or a salt thereof (see International Publication No. 2021 / 224323).

[0016] Alternatively, compound I can be prepared by the reaction of carboxylic acid VI with amine VII, as described in International Publication No. 2023 / 025617: [ka]

[0017] Carboxylic acid VI is commercially available or can be prepared by known methods from the literature (e.g., International Publication No. 2019 / 197468). Amine VII can be prepared from compound IVa in two steps: [ka]

[0018] The reactions of compound IVa with pyrimidinohydrazine (including subsequent Boc- group cleavage) are known from International Publication No. 2019 / 197468. The reaction of IVa with V via VIIa to obtain VII can be carried out under the conditions described in International Publication No. 2019 / 197468.

[0019] The reaction mixture is finished by conventional methods, for example, by mixing with water, extracting with a suitable organic solvent, separating the phases, and, where appropriate, by chromatographic purification of the crude product. Some intermediates and final products are obtained in the form of a colorless or slightly brownish viscous oily substance, which is purified from or removed from volatile components under reduced pressure and a moderately elevated temperature. If intermediates and final products are obtained as solids, purification may also be carried out by recrystallization or hot immersion.

[0020] If individual compounds I cannot be obtained by the pathway described above, they can be prepared by derivatization of other compounds I.

[0021] However, when a mixture of isomers is obtained by synthesis, separation is generally not always necessary, as in some cases, the individual isomers may interconvert during testing for use or during application (e.g., under the action of light, acid, or base). Such conversions may also occur after use, for example, in the treatment of treated plants or in the control of pests.

[0022] The group of organic parts mentioned in the above definition of variable elements, like the term halogen, is a general term for a list that enumerates each individual component of that group. (Prefix C) n -C m This indicates the number of possible carbon atoms in the group in each case.

[0023] The term "partially or completely substituted" by a group generally means that the group is substituted with the same or a different group.

[0024] The term "halogen" in each case means fluorine, bromine, chlorine, or iodine, and in particular fluorine, chlorine, or bromine.

[0025] In this specification, and when used in reference to the alkyl portion of alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, and alkoxyalkyl groups, the term "alkyl" refers, in each case, to a linear or branched alkyl group having typically 1 to 10 carbon atoms, frequently 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and more preferably 1 to 3 carbon atoms. Examples of alkyl groups include methyl (Me), ethyl (Et), n-propyl (n-Pr), isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl.

[0026] In this specification, and when used in reference to the haloalkyl carbonyl, haloalkoxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy, and haloalkoxyalkyl haloalkyl moieties, the term "haloalkyl" refers to a linear or branched alkyl group having typically 1 to 10 carbon atoms, frequently 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, in which the hydrogen atoms of the group are partially or completely substituted with halogen atoms. Preferred haloalkyl moieties are selected from C1-C4-haloalkyls, more preferably from C1-C3-haloalkyls or C1-C2-haloalkyls, particularly from C1-C2-fluoroalkyls such as fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, and pentafluoroethyl.

[0027] As used herein, the term “alkoxy” refers to a linear or branched alkyl group, in each case, having typically 1 to 10 carbon atoms, frequently 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, bonded via an oxygen atom. Examples of alkoxy groups include methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, isobutyloxy, and tert-butyloxy.

[0028] As used herein, the term “alkoxyalkyl” refers to alkyl groups that typically contain 1 to 10 carbon atoms, frequently 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms, having an alkoxy group that typically contains 1 to 4 carbon atoms, preferably 1 or 2 carbon atoms, with one carbon atom being as defined above. Examples include CH2OCH3, CH2-OC2H5, 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.

[0029] As used herein, the term "haloalkoxy" refers to a linear or branched alkoxy group having 1 to 10 carbon atoms, frequently 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, in each case in which the hydrogen atoms of the group are partially or completely substituted with halogen atoms, particularly fluorine atoms. Preferred haloalkoxy moieties include C1-C4 haloalkoxys, particularly C1-C2 fluoroalkoxys, such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, and the like.

[0030] As used herein, the term "alkylthio" (alkylsulfanil: S-alkyl) refers to a linear or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (=C1-C4-alkylthio), and more preferably 1 to 3 carbon atoms, bonded via a sulfur atom.

[0031] As used herein, the term "haloalkylthio" refers to the alkylthio group described above, in which a hydrogen atom is partially or completely substituted with fluorine, chlorine, bromine, and / or iodine.

[0032] The term "alkylsulfinyl" (alkylsulfoxyl: S(=O)-alkyl), as used herein, refers to a linear or branched saturated alkyl group (as described above) having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (=C1-C4-alkylsulfinyl), more preferably 1 to 3 carbon atoms, bonded at any position of the alkyl group via the sulfur atoms of the sulfinyl group.

[0033] As used herein, the term "haloalkylsulfinyl" refers to an alkylsulfinyl group as described above, in which a hydrogen atom is partially or completely substituted with fluorine, chlorine, bromine, and / or iodine.

[0034] The term "alkylsulfonyl" (S(=O)2-alkyl), as used herein, refers to a linear or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (=C1-C4-alkylsulfonyl), and preferably 1 to 3 carbon atoms, bonded at any position of the alkyl group via the sulfonyl group's sulfonyl atom.

[0035] As used herein, the term "haloalkylsulfonyl" refers to an alkylsulfonyl group as described above, in which a hydrogen atom is partially or completely substituted with fluorine, chlorine, bromine, and / or iodine.

[0036] The term "alkylcarbonyl" refers to an alkyl group, as defined above, that is bonded to the rest of the molecule via a carbon atom of the carbonyl group (C=O).

[0037] The term "haloalkylcarbonyl" refers to alkylcarbonyl groups, as described above, in which a hydrogen atom is partially or completely substituted with fluorine, chlorine, bromine, and / or iodine.

[0038] The term "alkoxycarbonyl" refers to an alkylcarbonyl group, as defined above, that is bonded to the rest of the molecule via an oxygen atom.

[0039] The term "haloalkoxycarbonyl" refers to the alkoxycarbonyl group described above, in which a hydrogen atom is partially or completely substituted with fluorine, chlorine, bromine, and / or iodine.

[0040] As used herein, the term "alkenyl" refers to a monounsaturated hydrocarbon group having typically 2 to 10 carbon atoms, frequently 2 to 6, preferably 2 to 4 carbon atoms, in each case, such as vinyl, allyl(2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl(2-methylpropa-2-en-1-yl), 2-buten-1-yl, 3-buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbuto-2-en-1-yl, 2-ethylprop-2-en-1-yl, etc.

[0041] As used herein, the term "haloalkenyl" refers to an alkenyl group as defined above, in which a hydrogen atom is partially or completely substituted with a halogen atom.

[0042] As used herein, the term "alkynyl" refers to a monounsaturated hydrocarbon group having typically 2 to 10 carbon atoms, frequently 2 to 6, preferably 2 to 4 carbon atoms, in each case, such as ethynyl, propargyl (2-propyne-1-yl), 1-propyne-1-yl, 1-methylprop-2-in-1-yl), 2-butyne-1-yl, 3-butyne-1-yl, 1-pentin-1-yl, 3-pentin-1-yl, 4-pentin-1-yl, 1-methylbuto-2-in-1-yl, 1-ethylprop-2-in-1-yl, etc.

[0043] As used herein, the term "haloalkynyl" refers to an alkynyl group as defined above, in which a hydrogen atom is partially or completely substituted with a halogen atom.

[0044] In this specification, and as used in reference to the cycloalkyl moieties of cycloalkoxys and cycloalkylthios, the term "cycloalkyl" means, in each case, a monocyclic or alicyclic group having 3 to 10 or 3 to 6 carbon atoms, such as cyclopropyl (cC3H5), cyclobutyl (cC4H7), cyclopentyl (cC5H9), and cyclohexyl (cC6H 11 ), cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, etc.

[0045] In this specification, and as used in reference to the halocycloalkyl moieties of halocycloalkoxys and halocycloalkylthios, the term "halocycloalkyl" refers to a monocyclic or alicyclic group, typically having 3 to 10 carbon atoms or 3 to 6 carbon atoms, in which case at least one hydrogen atom, e.g., 1, 2, 3, 4, or 5, is substituted with a halogen, particularly fluorine or chlorine. Examples include 1- and 2-fluorocyclopropyl, 1,2-, 2,2- and 2,3-difluorocyclopropyl, 1,2,2-trifluorocyclopropyl, 2,2,3,3-tetrafluorocyclopropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichlorocyclopropyl, 2,2,3,3-tetrachlorocyclopropyl, 1-, 2- and 3-fluorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, and 2,5-difluorocyclopentyl, 1-, 2- and 3-chlorocyclopentyl, and 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, and 2,5-dichlorocyclopentyl.

[0046] In this specification, and as used in reference to the halocycloalkenyl moieties of halocycloalkenyloxy and halocycloalkenylthio, the term "halocycloalkenyl" refers to a monocyclic monounsaturated nonaromatic group having typically 3 to 10 carbon atoms, for example 3 or 4 or 5 to 10, preferably 3 to 8 carbon atoms, in which at least one hydrogen atom, e.g., 1, 2, 3, 4, or 5, is substituted with a halogen, particularly fluorine or chlorine. Examples include 3,3-difluorocyclopropen-1-yl and 3,3-dichlorocyclopropen-1-yl.

[0047] The term "cycloalkenylalkyl" refers to a cycloalkenyl group, as defined above, that is bonded to the remainder of the molecule via an alkyl group, such as a C1-C5 alkyl group or a C1-C4 alkyl group, and especially a methyl group (=cycloalkenylmethyl).

[0048] The terms "carbocyclic" or "carbocykryl" generally include monocyclic non-aromatic rings with 3 to 12 members, preferably 3 to 8 members or 5 to 8 members, more preferably 5 or 6 members, containing 3 to 12 carbon atoms, preferably 3 to 8 members or 5 to 8 members, more preferably 5 or 6 members. Preferably, the term "carbocyclic" encompasses cycloalkyl and cycloalkenyl groups as defined above.

[0049] The terms "heterocyclic" or "heterocyclyl" generally include monocyclic or heterocyclic nonaromatic groups with 3 to 12 members, preferably 3 to 6 members, and especially 6 members. Heterocyclic nonaromatic groups typically include 1, 2, 3, 4, or 5 heteroatoms, preferably 1, 2, or 3, selected from N, O, and S (S atoms as ring members may exist as S, SO, or SO2) and optionally 1 or 2 C(O) groups as ring members. Examples of 5-membered or 6-membered heterocyclic groups include saturated or unsaturated non-aromatic heterocyclic rings, such as oxylanyl, oxetanyl, thietanyl, thietanyl-S-oxide (S-oxothietanyl), thietanyl-S-dioxide (S-dioxothietanyl), pyrrolidinyl, pyrrolinyl, pyrazolinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, thiolanyl, S-oxothiolanyl, S-dioxothiolanyl, dihydrothienyl, S-oxodihydrothienyl, S-dioxodihydrothienyl, oxazolidinyl, oxazolinyl, thiazolinyl These include oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydropyranyl, tetrahydropyranyl, 1,3- and 1,4-dioxanyl, thiopyranyl, S-oxothiopyranyl, S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodihydrothiopyranyl, S-dioxodihydrothiopyranyl, tetrahydrothiopyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothiomorpholinyl, thiadinyl, etc. Examples of heterocyclic rings containing one or two carbonyl groups as ring members include pyrrolidine-2-onyl, pyrrolidine-2,5-dionyl, imidazolidinyl-2-onyl, oxazolidine-2-onyl, and thiazolidinyl-2-onyl.

[0050] The term "hetalil" includes monocyclic five-membered or six-membered heteroaromatic groups that contain one, two, three, or four heteroatoms selected from N, O, and S as ring members. Examples of 5- or 6-membered heteroaromatic groups include pyridyl, i.e., 2-, 3- or 4-pyridyl; pyrimidinyl, i.e., 2-, 4- or 5-pyridinyl; pyrazinyl, pyridadinyl, i.e., 3- or 4-pyridadinyl; thienyl, i.e., 2- or 3-thienyl; furyl, i.e., 2- or 3-furyl; pyrrolyl, i.e., 2- or 3-pyrolyl; oxazolyl, i.e., 2-, 3- or 5-oxazolyl; isoxazolyl, i.e., 3-, 4- or 5-isoxazolyl; thiazolyl, i.e., 2-, 3- or 5-thiazolyl; isothiazolyl, i.e., 3-, 4- or 5-isothiazolyl; pyrazolyl, i.e., 1-, 3-, 4- or 5-pyrazolyl, i.e., 1-, 2-, 4- or 5-imidazolyl; and oxy Examples include sadiazolyls, such as 2- or 5-[1,3,4]oxadiazolyl, 4- or 5-(1,2,3-oxadiazole)yl, 3- or 5-(1,2,4-oxadiazole)yl, 2- or 5-(1,3,4-thiadiazole)yl, thiadiazolils, such as 2- or 5-(1,3,4-thiadiazole)yl, 4- or 5-(1,2,3-thiadiazole)yl, 3- or 5-(1,2,4-thiadiazole)yl, triazolils, such as 1H-, 2H- or 3H-1,2,3-triazole-4-yl, 2H-triazole-3-yl, 1H-, 2H- or 4H-1,2,4-triazolyl, and tetrazolyls, i.e., 1H- or 2H-tetrazolyl. The term "hetalial" also includes bicyclic 8- to 10-membered heteroaromatic groups containing one, two, or three heteroatoms selected from N, O, and S as ring members, where a 5 or 6-membered heteroaromatic ring is condensed with a phenyl ring or a 5 or 6-membered heteroaromatic group. Examples of 5 or 6-membered heteroaromatic rings condensed with a phenyl ring or a 5 or 6-membered heteroaromatic group include benzofuranyl, benzothienyl, indolyl, indazolyl, benzimidazolyl, benzooxathiazolyl, benzooxadiazolyl, benzothiadiazolyl, benzooxazinyl, quinolinyl, isoquinolinyl, purinyl, 1,8-naphthilidyl, pteridyl, pyrido[3,2-d]pyrimidyl, or pyridoimidazolyl.These condensed hetalil groups can be bonded to the remainder of the molecule via any ring atom of a 5- or 6-membered heteroaromatic ring or a carbon atom of the condensed phenyl moiety.

[0051] The terms "heterocyclylalkyl" and "hetalylalkyl" refer to heterocyclyl or hetalyl as defined above, which are bonded to the remainder of the molecule via a C1-C5-alkyl group or a C1-C4-alkyl group, particularly a methyl group (=heterocyclylmethyl or hetalylmethyl, respectively).

[0052] The terms "arylalkyl" and "phenylalkyl" refer to aryl and phenyl compounds, as defined above, that are bonded to the remainder of a molecule via a C1-C5-alkyl group or a C1-C4-alkyl group, particularly a methyl group (=arylmethyl or phenylmethyl), respectively. Examples include benzyl, 1-phenylethyl, 2-phenylethyl, and 2-phenoxyethyl.

[0053] The terms "alkylene," "cycloalkylene," "heterocycloalkylene," "alkenylene," "cycloalkenylene," "heterocycloalkenylene," and "alkynylene" refer to alkyl, cycloalkyl, heterocycloalkyl, alkenyl, cycloalkenyl, heterocycloalkenyl, and alkynyl groups as defined above, which are bonded to the remainder of the molecule via two atoms of each group, preferably via two carbon atoms, so as to form a linker between the two parts of the molecule.

[0054] In certain embodiments, the variable elements of the compound of formula I have the following meanings, which, both individually and in combination with each other, represent specific embodiments of the compound of formula I.

[0055] Embodiments of the present invention and preferred compounds for use in pest control and insecticidal applications are outlined in the following paragraphs.

[0056] With respect to the variable elements, a particularly preferred embodiment of the intermediate corresponds to an embodiment of the compound of formula I.

[0057] In a preferred embodiment, compound I exists in the form of a mixture of compounds IS and IR, wherein compound IS, having an S configuration of a carbon atom near nitrogen, is present in an amount greater than 50% by weight, particularly at least 70% by weight, more specifically at least 85% by weight, and more specifically at least 90% by weight, relative to the total weight of compounds IS and IR. The compound of formula IS is a particularly preferred embodiment of the present invention. [ka]

[0058] In one particularly preferred embodiment of the present invention, the method comprises the step of bringing a plant, a part thereof, its plant propagation material, a pest, its food source, habitat or breeding ground into contact with a pest-killing effective amount of a compound of formula IS.

[0059] R 1 Preferably, is H, C1-C6-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C6-cycloalkyl, or C1-C4-alkyl-C3-C6-cycloalkyl, more preferably H, CH3, C2H5, CH2cC3H5, CH2CH=CH2, or CH2C≡CH, particularly H or CH2cC3H5.

[0060] R 2 Preferably, it is CH3.

[0061] X is preferably CH or CR 3 , in particular, CH. Such compounds correspond to formula I.1. [ka]

[0062] In another embodiment, X is N. Such a compound corresponds to formula I.2. [ka]

[0063] R 3 is preferably halogen, CN, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C4-cycloalkyl (unsubstituted or substituted with one or more CN or halogen), C3-C4-halocycloalkyl, S(O) m -C1-C4-alkyl, S(O) m -C1-C4-haloalkyl, S(O) m --(substituted phenyl); in particular, selected from F, Cl, Br, I, CN, CF3, CHF2, OCH3, OC2H5, OcC3H5, O(4-F-C6H4), OCF3, OCHF2, 1-CN-cC3H4, 1-F-cC3H4, 2,2-F2-cC3H3, SO2CH3, SO2CH(CH3)2, SO2CF3, SO2(4-F-C6H4), and C(CH3)2CN.

[0064] In another embodiment, R 3 is halogen, CN, C1-C4-haloalkyl, C1-C4-haloalkoxy, C3-C4-cycloalkyl (unsubstituted or substituted with one or more CN or halogen), C3-C4-halocycloalkyl, O-S(O) m -halomethyl, O-S(O) m -C3-C4-cycloalkyl (unsubstituted or substituted with one or more CN or halogen), S(O) m -C1-C4-alkyl, S(O) m -C1-C4-haloalkyl, S(O) m --(substituted phenyl); in particular, selected from F, Cl, Br, I, CN, CF3, CHF2, OCH3, OC2H5, OcC3H5, O(4-F-C6H4), OCF3, OCHF2, 1-CN-cC3H4, 1-F-cC3H4, 2,2-F2-cC3H3, OSO2CF3, OSO2cC3H5, SO2CH3, SO2CH(CH3)2, SO2CF3, SO2(4-F-C6H4), and C(CH3)2CN.

[0065] R 3 is more preferably selected from Cl, Br, CF3, 1-CN-cC3H4, C(CH3)2CN, SO2CF3, SO2(4-F-C6H4), OCHF2. (R 3 ) n Specific preferred embodiments of are 3,5-(CF3)2; 3-CF3,5-Cl; 3-CF3,5-Br; 3-(1-CN-cC3H4),5-Cl; 3-C(CH3)2CN,5-Cl; 3-SO2CF3,5-Cl; 3-SO2(4-F-C6H4),5-Cl; 3-OCHF2,5-Cl.

[0066] R 3 is more preferably selected from Br, Cl, CF3, SO2(4-F-C6H4), 1-CN-cC3H4.

[0067] R bonded to the N atom of a saturated or unsaturated heterocycle 3 is preferably R 3b : C1-C4-alkyl, C3-C6-cycloalkyl, C1-C6-haloalkyl, C3-C6-halocycloalkyl, C1-C6-alkenyl, C1-C6-alkynyl, C3-C6-cycloalkyl-C1-C6-alkyl, C1-C6-alkyl-C3-C6-cycloalkyl (these are unsubstituted or substituted with R 3a ); C(O)NR 12 R 13 、C(O)OR 14 、C(O)R 15 、S(O) m -R 15 selected from.

[0068] In another preferred embodiment, at least one R 3 ) n group in 3 is R 3d:C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl-C1-C6-alkyl, C1-C6-alkyl-C3-C6-cycloalkyl (these are unsubstituted or R 3a It is replaced by );NR 12 R 13 , C(O)NR 12 R 13 , C(O)OR 14 , C(O)R 15 , and S(O) m -R 15 (where m is either 1 or 2) is selected.

[0069] R 3 In this, the exponent m is preferably 2. The exponent n is preferably 2. In a particular embodiment, one of the two R 3 The base is R 3d Selected from, the other is R 3 With respect to this, it is either as defined above or preferred.

[0070] (R 3 ) n R inside 3 The group is preferably located at positions 3 and 5.

[0071] R 4 The pyridine is preferably selected from pyridine, pyrimidine, pyrazine, pyridazine, thiazole, oxazole, pyrazole, and triazole, particularly 2-pyridine and 3-pyridine.

[0072] In another preferred embodiment, R 4 It is a heterocycline bonded via a ring of C atoms, and the ring is R 3 It is being replaced by an arbitrary choice.

[0073] In another preferred embodiment, R 4 It is a heterocycline bonded via a ring N atom, and the ring is R 3 It is being replaced by an arbitrary choice.

[0074] In another preferred embodiment, R 4 R 3 Selected from azetidine, oxetane, thietan, thietan-1-oxide, and thietan-1,1-dioxide substituted with, in particular, R 3d Selected from N-substituted 3-azetidine, thietan, thietan-1-oxide, and thietan-1,1-dioxide.

[0075] R 4 The more preferably selected from 2-pyridinyl, 3-pyridinyl, 2-thiazolyl, 1-pyrazolyl, 3-thietanyl, 3-(1-oxo-thietanyl), 3-(1,1-dioxo-thietanyl), and 3-(N-acetyl)azetidinyl.

[0076] In another preferred embodiment, R 4 The compound is selected from 2-imidazolyl, 3-(1,2,4-triazolyl), 3-pyrazolyl, 4-pyrazolyl, 4-(1,2,3-triazolyl), and 5-tetrazolyl.

[0077] In another preferred embodiment, R 4 It is 1-pyrazolyl.

[0078] In another preferred embodiment, R 4 It is 2-thiazolyl.

[0079] In another preferred embodiment, R 4 C1-C6-haloalkyl, OR 14 , NR 12 R 13 , or C(O)NR 12 R 13 R selected from 3 It is a five-membered heteroaromatic ring substituted with [a specific compound].

[0080] In another preferred embodiment, R 4 The ring is C1-C6-haloalkyl, OR 14 , NR 12 R13 , or C(O)NR 12 R 13 R selected from 3 Selected from phenyl or pyridyl substituted with .

[0081] Another embodiment is R 4 is phenyl or hetalil, and (R 3 ) n at least one R inside 3 The base is R 3d Compound I is selected from the following.

[0082] R 5 The element is preferably H, a halogen, a C1-C4-alkyl, or a C3-C6-cycloalkyl, more preferably H, F, Cl, CH3, or cC3H5. 5 However, it is more preferable that it be H or cC3H5. 5 It is particularly preferable that it is H.

[0083] In another embodiment, R 10 This includes H, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C3-C4-cycloalkylC1-C2-alkyl, C3-C4-halocycloalkyl-C1-C2-alkyl, C(O)-C1-C4-alkyl, C(O)-C1-C4-haloalkyl, C(O)-C3-C4-cycloalkyl, C(O)-C3-C4-halocycloalkyl or phenyl (unsubstituted or R 3a (It is partially or completely replaced by it.)

[0084] In particular, from the standpoint of their use, the compounds of formula I compiled in the following table are preferred. Each of the groups mentioned with respect to substituents in the table is, in itself, independently of the combination in which it is mentioned, a particularly preferred embodiment of the substituent in question. [ka]

[0085] Table 1:R 4 It is 2-pyridinyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0086] Table 2:R 4 It is 3-pyridinyl, and the R related to the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0087] Table 3:R 4 It is 2-thiazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0088] Table 4:R 4 It is N-pyrazolyl, and R related to the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0089] Table 5:R 4 The compound is 3-thietanyl, and the R is related to the compound. 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0090] Table 6:R 4 is 3-(N-acetyl)azetidinyl, and R related to the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0091] Table 7 R 4 is 2-imidazolyl, and R related to the compound1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0092] Table 8 R 4 The compound is 3-(1,2,4-triazolyl) and R is related to the compound. 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0093] Table 9 R 4 It is 3-pyrazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0094] Table 10 R 4 It is 4-pyrazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0095] Table 11 R 4 The compound is 4-(1,2,3-triazolyl) and the R is related to the compound. 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0096] Table 12 R 4 It is 5-tetrazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.1* in a row in Table A.

[0097] Table 13:R 4 It is 2-pyridinyl, and the R of the compound 1 and (R 3 )n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0098] Table 14:R 4 It is 3-pyridinyl, and the R related to the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0099] Table 15:R 4 It is 2-thiazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0100] Table 16:R 4 It is N-pyrazolyl, and R related to the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0101] Table 17:R 4 The compound is 3-thietanyl, and the R is related to the compound. 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0102] Table 18:R 4 is 3-(N-acetyl)azetidinyl, and R related to the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0103] Table 19 R 4 is 2-imidazolyl, and R related to the compound 1 and (R 3 ) nEach combination corresponds to a compound of formula I.2* in one row of Table A.

[0104] Table 20 R 4 The compound is 3-(1,2,4-triazolyl) and R is related to the compound. 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0105] Table 21 R 4 It is 3-pyrazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0106] Table 22 R 4 It is 4-pyrazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0107] Table 23 R 4 The compound is 4-(1,2,3-triazolyl) and the R is related to the compound. 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0108] Table 24 R 4 It is 5-tetrazolyl, and the R of the compound 1 and (R 3 ) n Each combination corresponds to a compound of formula I.2* in one row of Table A.

[0109] [Table 1]

[0110] [Table 2]

[0111] [Table 3]

[0112] The term "compound of the present invention" refers to the compound of formula I or "compound I," and includes its salts, tautomers, stereoisomers, and N-oxides.

[0113] The present invention also relates to an agricultural chemical composition comprising an auxiliary agent and at least one compound I.

[0114] The pesticide composition contains an effective amount of compound I to kill pests.

[0115] Compound I can be converted into conventional types of pesticide compositions, such as liquids, emulsions, suspensions, powders, sprays, pastes, granules, compresses, capsules, and mixtures thereof. Examples of composition types include suspensions (e.g., SC, OD, FS), emulsifying concentrates (e.g., EC), emulsions (e.g., EW, EO, ES, ME), capsules (e.g., CS, ZC), pastes, pastilles, wettable powders or powders (e.g., WP, SP, WS, DP, DS), compresses (e.g., BR, TB, DT), granules (e.g., WG, SG, GR, FG, GG, MG), insecticidal articles (e.g., LN), and gel formulations for the treatment of plant propagation materials (e.g., seeds) (e.g., GF). These and further composition types are defined in “Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6th Ed. May 2008, CropLife International. The composition is prepared by known methods, for example, Mollet and Grubemann, Formulation technology, Wiley VCH, Weinheim, 2001; or Knowles, New developments in crop protection product formulation, Agrow Reports DS243, T&F Informa, London, 2005.

[0116] Suitable auxiliary agents include solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetting agents, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesives, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, bactericides, antifreeze agents, defoaming agents, colorants, tackifiers, and binders.

[0117] Suitable solvents and liquid carriers are water and organic solvents. Suitable solid carriers or fillers are mineral earths.

[0118] Suitable surfactants are surfactant compounds, such as anionic, cationic, nonionic, and amphoteric surfactants, block polymers, and polyelectrolytes. Such surfactants can be used as emulsifiers, dispersants, solubilizers, wetting agents, penetration enhancers, protective colloids, or auxiliaries. Surfactants are listed in McCutcheon's, Vol. 1: Emulsifiers & Detergents, McCutcheon's Directories, Glen Rock, USA, 2008 (International or North American Ed.). Suitable anionic surfactants are alkali salts, alkaline earth salts, or ammonium salts of sulfonates, sulfates, phosphates, carboxylates. Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-type surfactants, and polymer-based surfactants. Suitable cationic surfactants are quaternary surfactants.

[0119] The pesticide composition generally contains 0.01 to 95% by weight of the active substance, preferably 0.1 to 90% by weight, and most preferably 0.5 to 75% by weight. The active substance is used with a purity of 90% to 100%, preferably 95% to 100%.

[0120] Various types of oils, wetting agents, auxiliaries, or fertilizers can be added as a premix to the active substance or a composition containing them, or, where appropriate, immediately before use (tank mix). These agents can be mixed with the composition according to the present invention in a weight ratio of 1:100 to 100:1.

[0121] Users typically apply the compositions according to the present invention from a predosage device, backpack sprayer, spray tank, spray aircraft, or irrigation system. Typically, the pesticide composition is prepared using water, buffer solution, and / or further additives to achieve the desired application concentration, thus yielding a ready-to-use spray solution or pesticide composition according to the present invention. Typically, 20 to 2000 liters of ready-to-use spray solution are applied per hectare of agriculturally useful area.

[0122] Compound I is suitable for use in protecting crops, plants, plant propagation materials (e.g., seeds), or the soil or water in which plants are growing from attacks or parasitism by animal pests. Accordingly, the present invention also relates to a method of protecting plants, comprising contacting crops, plants, plant propagation materials (e.g., seeds), or the soil or water in which plants are growing with a biocideously effective amount of Compound I, which are to be protected from attacks or parasitism by animal pests.

[0123] Compound I is also suitable for use in controlling or eliminating animal pests. Accordingly, the present invention also relates to a method for controlling or eliminating animal pests, comprising contacting animal pests, their habitats, breeding grounds or food sources, or crops, plants, plant propagation materials, such as seeds, or soil or areas, materials or environments in which animal pests are growing or can grow, with a pest-killing amount of Compound I.

[0124] Compound I is effective at any and all developmental stages, including eggs, larvae, pupae, and adults, through both contact and ingestion.

[0125] Compound I can be applied either on its own or in the form of a composition containing it.

[0126] Application can be carried out both before and after infestation of crops, plants, and plant propagation materials by pests.

[0127] The term "contact" includes both direct contact (applying a compound / composition directly to an animal pest or plant) and indirect contact (applying a compound / composition to a dwelling).

[0128] The term "animal pests" includes arthropods, gastropods, and nematodes. Preferred animal pests according to the present invention are arthropods, preferably insects and spiders, and especially insects.

[0129] The term "plants" includes: cereals, e.g., durum and other wheat, rye, barley, rye, oats, rice, or maize (feed maize and sugar maize / sweet corn and field corn); beets, e.g., sugar beets, or fodder beets; fruits, e.g., pomes, drupes, or soft fruits, e.g., apples, pears, plums, peaches, nectarines, almonds, cherries, papayas, strawberries, raspberries, blackberries, or gooseberries; legumes, e.g., beans, lentils, peas, alfalfa, or soybeans; oil plants, e.g., rapeseed, mustard, olives, sunflowers, palms, cocoa beans, castor beans, oil palms, peanuts, or soybeans; cucurbits, e.g., pumpkins, cucumbers, or melons. N; fiber plants, e.g., cotton, flax, hemp or jute; citrus fruits, e.g., oranges, lemons, grapefruit or mandarins; vegetables, e.g., eggplant, spinach, lettuce (e.g., iceberg lettuce), chicory, cabbage, asparagus, carrots, onions, garlic, leeks, tomatoes, potatoes, melons or sweet peppers; laurel plants, e.g., avocado, cinnamon or camphor; energy plants and raw material plants, e.g., corn, soybeans, rapeseed, sugarcane or oil palm; tobacco; nuts, e.g., walnuts; pistachios; coffee; tea; bananas; vines; hops; sweetleaf (stevia); natural rubber plants or ornamental plants and forest plants, shrubs, broad-leaved trees or evergreen trees, eucalyptus; turf; lawn; including grasses. Preferred plants include potatoes, sugar beets, tobacco, wheat, rye, barley, oats, rice, corn, cotton, soybeans, rapeseed, legumes, sunflowers, coffee, or sugarcane; fruits; vines; ornamental plants; or vegetables, such as cucumbers, tomatoes, beans, or pumpkins.

[0130] The term "seed" encompasses seeds and plant reproductive bodies (including true seeds, seed fragments, suckers, corms, bulbs, fruits, tubers, grains, cuttings, and severed shoots), and preferably means true seeds.

[0131] "Effective pest-killing dose" refers to the amount of active ingredient required to obtain an observable effect on growth (including effects related to necrosis, death, interference, prevention, and removal, destruction, or other effects related to the appearance and gradual reduction of the target organism's activity). The effective pest-killing dose may vary depending on the various compounds / compositions used in this invention. The effective pest-killing dose of a composition also varies depending on general conditions (e.g., desired pest-killing effect and duration, weather, target species, location, and application method).

[0132] When used to treat crop plants, for example by foliar application, the amount of the active ingredient of the present invention applied may range from 0.0001 g to 4000 g per hectare, for example, 1 g to 2 kg per hectare or 1 g to 750 g per hectare, preferably 1 g to 100 g per hectare.

[0133] Compound I is also suitable for use against non-crop insect pests. In this use against non-crop pests, Compound I can be used as a bait composition, gel, general insect spray, aerosol, in ultra-trace applications and as a mosquito net (impregnation or surface coating).

[0134] The term "non-crop insect pests" specifically refers to pests associated with non-crop targets, such as ants, termites, wasps, flies, ticks, mosquitoes, bed bugs, crickets, or cockroaches, such as Aedes aegypti, Musca domestica, and Tribolium spp.; termites, such as Reticulitermes flavipes and Coptotermes formosanus; cockroaches, such as Blatella germanica and Periplaneta Americana; and ants, such as Solenopsis invicta, Linepithema humile, and Camponotus pennsylvanicus.

[0135] The feed may be a liquid, solid, or semi-solid preparation (e.g., a gel). When used in a feed composition, the typical content of the active ingredient is 0.001% to 15% by weight, preferably 0.001% to 5% by weight of the active compound.

[0136] Compound I and its compositions can be used to protect not only wooden materials (e.g., wood, fences, railway ties, frameworks, artistic artifacts, etc.) and buildings from ants, termites and / or beetles that destroy wood or fibers, as well as construction materials, furniture, leather, textiles, vinyl products, electrical wires and cables, and to control damage to crops or people caused by ants and termites (e.g., when pests invade houses and public facilities or build nests in gardens, orchards or parks).

[0137] A typical application rate when protecting a material is, for example, 1 m of the material being treated. 2 The amount of active compound per unit is 0.001g to 2000g, or 0.01g to 1000g, preferably 1m 2 Each serving contains between 0.1g and 50g.

[0138] The insecticidal composition for use in impregnating materials typically contains 0.001 to 95% by weight, preferably 0.1 to 45% by weight, and more preferably 1 to 25% by weight of at least one repellent and / or insecticide.

[0139] The compounds of the present invention are effective against animal pests, for example: Suborders of the suborder Auchenorrhyncha, such as Amrasca biguttula, species of the genus Empoasca, Nephotettix virescens, Sogatella furcifera, species of the genus Mahanarva, Laodelphax striatellus, Nilaparvata lugens, and Diaphorina citri; Lepidoptera, for example, species of the genus Helicoverpa, such as Heliothis virescens, Lobesia botrana, Ostrinia nubilalis, Plutella xylostella, Pseudoplusia includens, Scirpophaga incertulas, species of the genus Spodoptera, such as Trichoplusia ni, Tuta absoluta, Cnaphalocrocis medialis, Cydia pomonella, and Chilo supressalis. *Chrysodeixis includens*, *Anticarsia gemmatalis*, *Agrotis ipsilon*, *Chrysodeixis includens*; Hemiptera insects, for example, species of the genus Lygus; true bugs, for example, species of the genus Euschistus, Halyomorpha halys, Nezara viridula, Piezodorus guildinii, Dichelops furcatus; Thrips, such as species of the genera Frankliniella, Thrips, and Dichromothrips corbettii; Aphids, such as the pea aphid (Acyrthosiphon pisum), cotton aphids (Aphis spp.), peach aphid (Myzus persicae), Rhopalosiphum spp., Schizaphis graminum, and Megoura viciae; Whiteflies, such as Trialeurodes vaporariorum and Bemisia species; Coleoptera, for example, species of the genera Phyllotreta, Melanotus, Meligethes aeneus, Leptinotarsa ​​decimlineata, Ceutorhynchus, Diabrotica, Anthonomus grandis, Atomaria linearia, Agriotes, and Epilachna; Flies, for example, species of the genus Delia, Ceratitis capitate, Bactrocera, and Liriomyza; Coccoidea, for example, Aonidiella aurantia and Ferrisia virgate; Arthropods (mites) of the class Arachnida, such as the grain mite (Penthaleus major) and species of the genus Tetranychus (Tetranychus spp.); Nematodes, such as Heterodera glycines, species of the genus Meloidogyne, species of the genus Pratylenchus, and Caenorhabditis elegans. It is particularly suitable for efficiently controlling arthropods, including insects, and nematodes.

[0140] Compound I is suitable for use in the treatment or defense against parasitic infestation or infection of animals. Accordingly, the present invention also relates to the use of the compound for the manufacture of pharmaceuticals for treating or defending animals against parasitic infestation or infection. Furthermore, the present invention relates to a method for treating or defending animals against parasitic infestation and infection, the method comprising administering or applying an effective amount of compound I to an animal orally, topically, or parenterally.

[0141] The present invention also relates to the non-therapeutic use of the compounds of the present invention for treating or defending animals from parasitic infestations and infections. Furthermore, the present invention relates to a non-therapeutic method for treating or defending animals from parasitic infestations and infections, the method comprising applying a parasitic-effective amount of compound I to the habitat.

[0142] The compounds of the present invention are more suitable for use in eradicating or controlling parasites in and on animals. Furthermore, the present invention relates to a method for eradicating or controlling parasites in and on animals, the method comprising contacting the parasite with a parasitekilling effective amount of compound I.

[0143] The present invention also relates to the non-therapeutic use of compound I for controlling or eliminating parasites. Furthermore, the present invention relates to a non-therapeutic method for eliminating or controlling parasites, comprising applying a parasitically effective amount of compound I to the habitat.

[0144] Compound I can be effective by either contact (through soil, glass, walls, mosquito nets, carpets, blankets, or animal parts) or ingestion (e.g., bait). Furthermore, Compound I can be applied to any and all stages of development.

[0145] Compound I can be applied either on its own or in the form of a composition containing it.

[0146] The term "habitat" means a place, food source, breeding ground, area, material, or environment in which a parasite grows or can grow outside of an animal.

[0147] As used herein, the term “parasite” includes endoparasites and ectoparasites. In some embodiments of the present invention, endoparasites may be preferred. In other embodiments, ectoparasites may be preferred. Parasitism of warm-blooded animals and fish includes lice, biting lice, ticks, rhinoceros flies, louse flies, stable flies, blowflies, flies, myiasis fly larvae, chiggers, black flies, mosquitoes, and fleas.

[0148] The compounds of the present invention are particularly useful for eradicating the following parasites: Cimex lectularius, Rhipicephalus sanguineus, and Ctenocephalides felis.

[0149] As used herein, the term “animal” includes warm-blooded animals (including humans) and fish. Mammals, such as cattle, sheep, pigs, camels, deer, horses, pigs, poultry, rabbits, goats, dogs and cats, buffalo, donkeys, fallow deer and reindeer are preferred, as are fur-bearing animals such as minks, chinchillas and raccoons, birds, such as hens, geese, turkeys and ducks, and fish, such as freshwater fish and saltwater fish, such as trout, carp and eels. Domesticated animals, such as dogs or cats, are particularly preferred.

[0150] Compound I can be administered in a total amount of 0.5 mg / kg to 100 mg / kg per day, preferably 1 mg / kg to 50 mg / kg per day.

[0151] For oral administration to warm-blooded animals, compound I can be formulated as animal feed, animal feed premix, animal feed concentrate, pills, liquids, pastes, suspensions, liquids, gels, tablets, boluses, and capsules. For oral administration, the animal should be supplied with 0.01 mg to 100 mg of compound I per kg of animal body weight per day, preferably 0.5 mg to 100 mg of compound I per kg of animal body weight per day, in the selected dosage form.

[0152] Alternatively, compound I may be administered to animals parenterally, for example, by intraruminant injection, intramuscular injection, intravenous injection, or subcutaneous injection. Compound I may be dispersed or dissolved in a physiologically acceptable carrier for subcutaneous injection. Alternatively, compound I may be formulated in an indwelling for subcutaneous administration. In addition, compound I may be administered transdermally to animals. For parenteral administration, the selected dosage form should provide animals with compound I at a dose of 0.01 mg / kg animal body weight to 100 mg / kg animal body weight per day.

[0153] Compound I can also be applied topically to animals in the form of dips, powders, sprays, collars, medals, sprays, shampoos, spot-on formulations, and pore-on formulations, as well as ointments or oil-in-water or water-in-oil emulsions. For topical application, dips and sprays typically contain 0.5 ppm to 5,000 ppm, preferably 1 ppm to 3,000 ppm, of Compound I. Furthermore, Compound I can be formulated as ear tags for animals, particularly tetrapods, such as cattle and sheep.

[0154] Oral solutions are administered directly.

[0155] Liquids applied to the skin may be dropped, spread, rubbed in, sprinkled, or sprayed.

[0156] The gel is applied to or spread on the skin, or introduced into a body cavity.

[0157] Pore-on formulations are applied or sprayed onto a limited area of ​​the skin, allowing the active compound to penetrate the skin and act systemically. Pore-on formulations are prepared by dissolving, suspending, or emulsifying the active compound in a suitable skin-compatible solvent or solvent mixture.

[0158] The emulsion may be administered orally, transdermally, or by injection.

[0159] The suspension can be administered orally or topically / transdermally.

[0160] The semi-solid preparation may be administered orally or topically / transdermally.

[0161] For the production of solid preparations, the active compound is mixed with a suitable excipient, and if appropriate, an auxiliary agent is added to obtain the desired shape.

[0162] The compositions that can be used in the present invention may generally contain about 0.001 to 95% of compound I.

[0163] The ready-to-use preparation contains a compound acting on parasites (preferably ectoparasites) at a concentration of 10 ppm to 80% by weight, preferably 0.1 to 65% by weight, more preferably 1 to 50% by weight, and most preferably 5 to 40% by weight.

[0164] The preparation to be diluted before use contains a compound acting on ectoparasites at a concentration of 0.5 to 90% by weight, preferably 1 to 50% by weight.

[0165] Furthermore, this preparation contains a compound of formula I acting on endoparasites at a concentration of 10 ppm to 2% by weight, preferably 0.05 to 0.9% by weight, and most particularly preferably 0.005 to 0.25% by weight.

[0166] The solid preparation that releases the compound of the present invention can be administered at a total amount of 10 mg to 300 mg, preferably 20 mg to 200 mg, and most preferably 25 mg to 160 mg per kg of the body weight of the animal to be treated over a period of 3 weeks.

Example

[0167] A. Preparation Example When this compound is determined by mass spectrometry (MS) combined with melting point determination, NMR spectroscopy, or HPLC analysis (HPLC-MS = high performance liquid chromatography coupled with mass spectrometry) or LC analysis (LC-MS = liquid chromatography coupled with mass spectrometry), its characteristics are evaluated by the mass-to-charge ratio ([m / z]) and the retention time (RT; [min]).

[0168] Method A: Shimadzu Nexera UHPLC + Shimadzu LCMS-2020, ESI; column: Kinetex 1.7μ XB-C18 100A, 2.1x50mm; mobile phase: A: water + 0.1% TFA; B: ACN; temperature: 60°C; gradient: 5% B to 100% B in 1.5 minutes; 100% B in 0.25 minutes; flow rate: 0.8 mL / min to 1.0 mL / min in 1.5 minutes; MS: ESI positive; mass range (m / z): 100 to 700.

[0169] Example 1: Synthesis of [N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide](I-1) Step 1: Synthesis of [[6-(2-pyridyl)pyrimidine-4-yl]aminoammonium chloride]: To a solution of 4-chloro-6-(2-pyridyl)pyrimidine (400 mg, 2.09 mmol, 1.00 equivalent) in EtOH (8 mL), hydrazine hydrate (0.12 mL, 125 mg, 2.51 mmol, 1.2 equivalents) was added at 0°C. The reaction mixture was stirred for 18 hours while warming to 20-25°C. Additional hydrazine hydrate (0.03 mL, 31.3 mg, 0.63 mmol, 0.3 equivalents) was added, and the reaction mixture was stirred for a further 3 days at 20-25°C. The precipitate was filtered to obtain [[6-(2-pyridyl)pyrimidine-4-yl]aminoammonium chloride] (330 mg, 1.48 mmol, 71%) as a white solid. LCMS: Desired mass: m / z = 188.1; Measured mass: m / z = 188.0.

[0170] Step 2: Synthesis of N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide: To a solution of N-[2-[dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]-3,5-bis(trifluoromethyl)benzamide (300 mg, 783 μmol, 1 equivalent) in AcOH (5 mL), [[6-(2-pyridyl)pyrimidine-4-yl]amino]ammonium chloride (158 mg, 704 μmol, 0.9 equivalents) was added at 20-25°C. The reaction mixture was stirred at 70°C for 4 hours and at 20-25°C for 17 hours. The solvent was removed under reduced pressure. The residue was dissolved in 40 mL of siRNA, washed with 3 × 30 mL of saturated NaHCO3 solution, dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (c-hexane:siRNA = 100:0 to 0:100) to obtain N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (100 mg, 177 μmol, 23%) as a white solid. LCMS: Desired mass: m / z = 508.1; Measured mass: m / z = 508.0. 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=9.80(d,J=6.8Hz,1H),9.32(d,J=1.1Hz,1H),8.82(d,J=1.1Hz,2H),8.51-8.47(m,3H),8 .35-8.30(m,2H),8.09(td,J=7.8,1.8Hz,1H),7.66(ddd,J=7.6,4.8,1.1Hz,1H),6.36-6.27(m,1H),1.70(d,J=7.0Hz,3H).

[0171] Example 2: Synthesis of [3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-[(1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]benzamide](I-2) Step 1: Synthesis of methyl 3-hydroxy-5-methyl benzoate: To a stirred solution of 3-hydroxy-5-methyl benzoic acid (110 g, 723 mmol, 1 equivalent) in MeOH (3 L), SOCl2 (173 g, 1.45 mol, 2 equivalents) was added dropwise. The mixture was stirred overnight at 60°C and concentrated to obtain methyl 3-hydroxy-5-methyl benzoate (118 g), which was used in the next step without further purification.

[0172] Step 2: Synthesis of methyl 3-(difluoromethoxy)-5-methylbenzoate: To a stirred solution of methyl 3-hydroxy-5-methylbenzoate (118 g, 710 mmol, 1 equivalent) in DMF (3.5 L), sodium 2-chloro-2,2-difluoroacetate (325 g, 2.13 mol, 3 equivalents) and cesium carbonate (463 g, 1.42 mol, 3 equivalents) were added under an inert atmosphere. The mixture was stirred overnight at 100°C. After cooling to 20-25°C, the solvent was evaporated, the residue was dissolved in water (6 L), and extracted with ethyl acetate (5 × 500 mL). The organic layer was dried over sodium sulfate and concentrated to obtain the crude product, which was purified by column chromatography to obtain methyl 3-(difluoromethoxy)-5-methylbenzoate (71.6 g, yield 46%).

[0173] Step 3: Synthesis of methyl 3-(bromomethyl)-5-(difluoromethoxy)benzoate: To a stirred solution of methyl 3-(difluoromethoxy)-5-methyl-benzoate (71.6 g, 0.33 mol, 1 equivalent) in dichloroethane (1 L), NBS (64.1 g, 0.36 mol, 1.1 equivalents) was added all at once. The mixture was refluxed overnight, cooled to 20-25°C, filtered through an SiO2 pad, and concentrated to obtain methyl 3-(bromomethyl)-5-(difluoromethoxy)benzoate (85.2 g, yield 79%).

[0174] Step 4: Synthesis of methyl 3-(cyanomethyl)-5-(difluoromethoxy)benzoate: To a stirred solution of methyl 3-(bromomethyl)-5-(difluoromethoxy)benzoate (85.2 g, 0.26 mol, 1 equivalent) in EtOH (1.7 L) and H2O (425 mL), KCN (33.9 g, 520 mmol, 2 equivalents) was added all at once. The mixture was stirred at 85 °C for 2 hours, cooled to 20-25 °C, and sodium carbonate (excess) was added. The mixture was extracted with RINKAN (3 × 200 mL). The organic layer was washed with water (2 × 300 mL), dried on sodium sulfate, and concentrated. The residue was purified by flash chromatography to obtain methyl 3-cyanomethyl-5-(difluoromethoxy)benzoate (16.8 g, yield 27%).

[0175] Step 5: Synthesis of methyl 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoate: To a stirred solution of methyl 3-cyanomethyl-5-(difluoromethoxy)benzoate (16.8 g, 70 mmol, 1 equivalent) in DMF (200 mL), Cs2CO3 (45.6 g, 0.14 mol, 2 equivalents) was added, followed by BrCH2CH2Br (39.4 g, 210 mmol, 3 equivalents). The mixture was stirred overnight at 120 °C, cooled to 20-25 °C, concentrated, and divided between siRNA (200 mL) and concentrated aqueous HCl (400 mL). The organic phase was separated, dried over Na2SO4, and concentrated to obtain crude methyl 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoate (17 g, yield 86%), which was used in the next step without further purification.

[0176] Step 6: Synthesis of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoic acid: To a stirred solution of methyl 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoate (17 g, 60 mmol, 1 equivalent) in THF (200 mL) / water (50 mL), NaOH (2.39 g, 60 mmol, 1 equivalent) was added at 0°C. The reaction mixture was stirred overnight at 20-25°C and divided between siRNA (200 mL) and HCl water (400 mL). The organic layer was separated, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography (CHCl3 / AcNACN / AcOH) to obtain 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoic acid (10 g, yield 66%). 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=13.51(bs,1H),7.85-7.81(m,1H),7.62-7.58(m,1H),7.37(t, 2 J FH =73.3Hz,1H),7.30-7.27(m,1H),1.89-1.77(m,2H),1.70-1.57(m,2H). LCMS: Desired mass: m / z = 253.2; Measured mass: m / z = 253.06

[0177] Step 7: Synthesis of (6-pyrazole-1-ylpyrimidine-4-yl)hydrazine: A solution of 4-chloro-6-pyrazole-1-ylpyrimidine (1.01 g, 5.59 mmol, 1 equivalent) and hydrazine hydrate (1.12 g, 22.4 mmol, 4 equivalents) in MeOH (35 mL) was stirred at 65°C for 4 hours until LC-MS showed complete conversion. The reaction mixture was diluted with H2O, and volatile substances were removed under reduced pressure. The remaining solution was adjusted to pH 8 using HCl water and K2CO3 water. The resulting precipitate was filtered, washed with H2O, and dried to obtain (6-pyrazole-1-ylpyrimidine-4-yl)hydrazine (920 mg, 5.22 mmol, 93%). 1H-NMR(400MHz,DMSO-d6)δ[ppm]=8.62(bs,1H),8.55(d,J=2.6Hz,1H),8.28(bs,1 H),7.83(d,J=1.6Hz,1H),7.22(bs,1H),6.55(dd,J=2.6,1.6Hz,1H),4.5(bs,2H).

[0178] Step 8: Synthesis of tert-butyl N-[(1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]carbamate: To a solution of (6-pyrazole-1-ylpyrimidine-4-yl)hydrazine (2.54 g, 10.4 mmol, 2 equivalents) in acetic acid (14 mL), tert-butyl N-[(1S)-2-[dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (920 mg, 5.22 mmol, 1 equivalent) was added dropwise at 20-25°C. The reaction mixture was stirred at 20-25°C for 19 hours until LC-MS showed complete conversion. The solvent was removed under reduced pressure, and the resulting solid was washed with MTBE. The residue was purified by flash chromatography on silica gel (c-hexane:siRNA = 100:0~0:100) to obtain N-[(1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]carbamate (1.00 g, 2.81 mmol, 54%) as a colorless wax.

[0179] Step 9: Synthesis of (1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethanamine: To a solution of tert-butyl N-[(1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]carbamate (1.00 g, 2.81 mmol, 1 equivalent) in 1,4-dioxane (30 mL), HCl (4N in 1,4-dioxane, 7 mL, 28 equivalents) was added. The reaction mixture was stirred at 50°C for 5 hours and at 60°C for 1 hour. The solvent was removed under reduced pressure to obtain (1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethanamine (842 mg) as a colorless solid. 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=9.14(d,J=1.1Hz,1H),8.90(bs,2 to 3H),8.77(d,J=2.8Hz,1H),8.50(s,1H),8 .27(d,J=1.1,1H),8.07-8.03(m,1H),6.74(dd,J=2.8Hz,1.6Hz,1H),5.57-5.47(m,1H),1.68(d,J=6.7Hz,3H).

[0180] Step 10: Synthesis of 3-(difluoromethoxy)-5-methyl-N-[(1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]benzamide: 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)benzoic acid (148 mg, 585 μmol, 1 equivalent), (1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4- Triazole-3-yl]ethaneamine (150 mg, 585 μmol, 1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (289 mg, 761 μmol, 1.3 equivalents), and N,N-diisopropylethylamine (0.25 mL, 189 mg, 1.46 mmol, 2.5 equivalents) were stirred at 20-25°C for 18 hours. The solvent was removed under reduced pressure. The residue was dissolved in toluene (10 mL), washed with H₂O (2 × 5 mL), dried over Na₂SO₄, filtered, and concentrated. The crude product was further purified by flash chromatography on silica gel (c-hexane:siRNA = 100:0~0:100) to obtain 3-(difluoromethoxy)-5-methyl-N-[(1S)-1-[2-(6-pyrazole-1-ylpyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]benzamide (233 mg, 450 μmol, 77%) as a beige wax. 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=9.29(d,J=7.0Hz,1H),9.10(d,J=1.1Hz,1H),8.76(d,J=2.6Hz,1H), 8.31(s,1H),8.26(d,J=1.0,1H),8.03(d,J=1.6Hz,1H),7.68-7.64(m,1H),7.59-7.56(m,1H),7.31(t, 2 J FH =73.5Hz,1H),7.28-7.26(m,1H),6.73(dd,J=2.8,1.6Hz,1H),6.31-6.23(m,1H),1.82-1.77(m,2H),1.66(d,J=7.0Hz,3H),1.63-1.58(m,2H). LCMS: Desired mass: m / z = 492.2; Measured mass: m / z = 492.1.

[0181] Example 3: Synthesis of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide (I-12) Step 1: Synthesis of 4-chloro-6-hydrazinylpyrimidine: To a mixture of 4,6-dichloropyrimidine (10.0 g, 67.1 mmol, 1 equivalent) in EtOH (50 mL), hydrazinium hydroxide (4.11 g, 80.5 mmol, 98% purity, 1.2 equivalents) was added dropwise at 0°C. The reaction mixture was stirred at 0°C for 2 hours and then filtered. The filtered cake was washed with EtOH (20 mL) and water (20 mL), dried, and obtained 4-chloro-6-hydrazinylpyrimidine as a white solid (4.2 g, 50% yield). 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=8.81(s,1H),8.17(s,1H),6.75(bs,1H),4.50(bs,2H).

[0182] Step 2: Synthesis of tert-butyl(1-(1-(6-chloropyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate: A mixture of 4-chloro-6-hydrazinylpyrimidine (3.7 g, 25.6 mmol, 1 equivalent) and tert-butyl N-[2-[dimethylaminomethyleneamino]-1-methyl-2-oxoethyl]carbamate (12.5 g, 51.2 mmol, 2 equivalents) in 1,4-dioxane (50 mL) was added dropwise with HCl (2 M in HCl, 20 mL). The reaction mixture was stirred at 25 °C for 16 hours. AcOH (20 mL) was added, and the reaction mixture was stirred at 50 °C for 2 hours. Volatile substances were removed under reduced pressure, and the residue was purified by column chromatography (DCM / MeOH=30 / 1) on silica gel to obtain tert-butyl(1-(1-(6-chloropyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate (3.17 g, yield 38%) as a white solid. LC-MS(ES)m / z(M+H) + =325.3.

[0183] Step 3: Synthesis of tert-butyl (1-(1-(6-(pyridin-2-yl)pyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate: A mixture of tert-butyl (1-(1-(6-chloropyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (2.87 g, 8.8 mmol, 1 eq), 2-(tributylstannyl)pyridine (3.24 g, 8.8 mmol, 1 eq), Pd(PPh3)4 (1.02 g, 0.88 mmol, 0.1 eq) and CuI (0.17 g, 0.88 mmol, 0.1 eq) in toluene (60 mL) was stirred at 110 °C for 2 h under N2. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2 × 100 mL). The combined organic phases were concentrated. The residue was purified by column chromatography on silica gel (DCM / MeOH = 19 / 1) to give the crude product, which was triturated with MeOH (20 mL) to afford tert-butyl (1-(1-(6-(pyridin-2-yl)pyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (1.4 g, 43% yield) as a white solid. 1 1H-NMR (400 MHz, DMSO-d6) δ [ppm] = 9.31 (s, 1H), 8.83 - 8.80 (m, 2H), 8.52 (d, J = 8.0 Hz, 1H), 8.28 (s, 1H), 8.11 - 8.06 (m, 1H), 7.67 - 7.63 (m, 1H), 7.57 (d, J = 7.6 Hz, 1H), 5.86 - 5.79 (m, 1H), 1.48 (d, J = 6.8 Hz, 3H), 1.32 (s, 9H).

[0184] Step 4: Synthesis of 1-(1-(6-(pyridin-2-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethane-1-amine hydrochloride: To a mixture of tert-butyl(1-(1-(6-(pyridin-2-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate (1.1 g, 3.0 mmol, 1 equivalent) in HCl (10 mL, 2 M in HCl) was added at 30°C, and the resulting mixture was stirred at 30°C for 2 hours. The mixture was filtered, the filtered cake was washed with dimethylammonium phosphate (10 mL), and dried under vacuum to obtain 1-(1-(6-(pyridin-2-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethane-1-amine hydrochloride as a white solid (830 mg, 90% yield). 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=9.36(s,1H),8.91(bs,3H),8.84-8.83(m,2H),8.54-8.52(m,1H),8.50(s,1 H),8.13-8.08(m,1H),7.69-7.66(m,1H),5.58-5.52(m,1H),1.70(d,J=6.8Hz,3H).LC-MS(ES)m / z(M+H-HCl) + =268.0.

[0185] Step 5: Synthesis of 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide: 3-(1-cyanocyclopropyl)-5(difluoromethoxy)benzoic acid (71.0 mg, 281 μmol, 1 equivalent), 1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide A solution of azole-3-yl]ethanamine (75 mg, 281 μmol, 1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (139 mg, 365 μmol, 1.3 equivalents), and N,N-diisopropylethylamine (0.12 mL, 91.0 mg, 0.70 mmol, 2.5 equivalents) was stirred at 20-25°C for 5 days. The solvent was then removed under reduced pressure, the residue was redissolved in SiO (10 mL), washed with H₂O (2 × 5 mL), dried over Na₂SO₄, filtered, and concentrated. The crude product was further purified by two consecutive flash chromatography steps. The first flash chromatography purification step was carried out using silica gel (c-hexane:siRNA = 100:0~0:100), and the second flash chromatography purification step was carried out using an RP-18 column (H2O:CH3CN = 100:0~0:100) to obtain 3-(1-cyanocyclopropyl)-5-(difluoromethoxy)-N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide (35 mg, 70 μmol, 25%) as a colorless solid. 1 H-NMR (400MHz, acetone-d6) δ[ppm]=9.29(d,J=1.2Hz,1H),8.98(d,J=1.3Hz,1H,)8.84-8.80(m,1H),8.60(dt,J=7.9,1.1Hz,1H),8.5 5(d,J=7.6Hz,1H),8.14(s,1H),8.07(td,J=7.8,1.8Hz,1H),7.74(t,J=1.6Hz,1H),7.67-7.60(m,2H),7.33-7.30(m,1H),7.09(t, 2 J FH=73.7Hz,1H),6.51-6.43(m,1H),1.81-1.77(m,2H),1.73(d,J=7.0Hz,3H),1.63-1.58(m,2H).LCMS: Desired mass: m / z=503.5; Actual mass: m / z=503.1.

[0186] Example 4: Synthesis of N-(cyclopropylmethyl)-N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (I-14) Step 1: Synthesis of N-(cyclopropylmethyl)-1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethaneamine (I-14): A solution of 1-(1-(6-(pyridin-2-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethane-1-amine hydrochloride (90 mg, 337 μmol, 1 equivalent), cyclopropane carbaldehyde (26.0 mg, 370 μmol, 1.1 equivalents), sodium borohydride (42.3 mg, 673 μmol, 2 equivalents), and AcOH (5.06 mg, 84 μmol, 0.25 equivalents) in MeOH (2 mL) was stirred at 20-25°C for 18 hours. Further cyanoboron hydride (42.3 mg, 0.673 mmol, 2 equivalents) was added and the mixture was stirred for 7 hours. Subsequently, sodium borohydride (25.5 mg, 370 μmol, 1.1 equivalents), 3 Å molecular sieve (1 g), and cyclopropanecarbaldehyde (26.0 mg, 370 μmol, 1.1 equivalents) were added, and the mixture was stirred for a further 21 hours. Sodium cyanoboron hydride was added (42.3 mg, 673 μmol, 2 equivalents), and the mixture was stirred for 16 hours. The reaction was quenched with H2O (10 mL) and extracted with RINKAN (2 × 5 mL). The organic layer was washed with H2O (2 × 5 mL), dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography on silica gel (c-hexane:siRNA = 100:0~0:100) to obtain N-(cyclopropylmethyl)-1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethanamine (20 mg, 62 μmol, 18%). LCMS: Desired mass: m / z = 322.2; Measured mass: m / z = 321.9.

[0187] Step 2: Synthesis of N-(cyclopropylmethyl)-N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide: N-(cyclopropylmethyl)-1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethanolamine (18 mg) in DMF (3 mL) A solution of 56 μmol, 1 equivalent of 3,5-bis(trifluoromethyl)benzoic acid (14.5 mg, 56 μmol, 1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (27.7 mg, 73 μmol, 1.3 equivalents), and N,N-diisopropylethylamine (0.024 mL, 18.1 mg, 140 μmol, 2.5 equivalents) was stirred at 20-25°C for 16 hours. The solvent was then removed under reduced pressure, the residue was dissolved in HCl (10 mL), washed with H₂O (2 × 5 mL), dried over Na₂SO₄, filtered, and the solvent was removed. The crude product was purified by flash chromatography on silica gel (c-hexane:siRNA = 100:0~40:60) to obtain N-(cyclopropylmethyl)-N-[1-[2-[6-(2-pyridyl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (18 mg, 32 μmol, 57%). 1 H-NMR(400MHz,acetone-d6)δ[ppm]=9.46-8.90(m,1H),8.92(bs,1H),8.81(ddd,J=4.8, 1.8,0.9Hz,1H),8.57(d,J=8.0Hz,1H),8.23(s,1H),8.06(td,J=7.7,1.8Hz,2H),7.62 (d,J=1.7Hz,2H),7.62(ddd,J=7.6,4.7,1.2Hz,1H),6.90-6.39(m,1H),4.69-3.80(m ,1H),3.68-2.94(m,2H),1.88(d,J=7.0Hz,3H),1.02-0.53(m,2H),0.50-0.15(m,2H). LCMS: Desired mass: m / z(M+H) +=562.2;Actual mass: m / z=562.1.

[0188] Example 5: N-[1-[2-[6-(1-meacetylazetidine-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide(I-16) Step 1: Synthesis of tert-butyl(1-(1-(6-(1-acetylazetidine-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate: tert-butyl N-[1-[2-(6-chloropyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]carbamate (15.0 g, 46.2 mmol, 1 equivalent) and 1-acetylazetidine-3-carboxylic acid (9.9 g, 69.3 mmol, 1.5 equivalents) in DMAC (10 mL) A mixture of 2,2'-bipyridine 4,4'-bis(1,1-dimethylethyl) (1.86 g, 6.9 mmol, 0.1 equivalent), dichloro(1,2-dimethoxyethane)nickel (1.02 g, 4.6 mmol, 0.05 equivalent), Cs2CO3 (22.58 g, 69.3 mmol, 1.5 equivalent), and [Ir{dF(CF3)ppy}2(dtbpy)]PF6 (1.55 g, 1.4 mmol, 0.03 equivalent) was stirred under nitrogen at 20-25°C overnight while being irradiated with 450 nm (LED). The reaction mixture was diluted with water (50 mL) and extracted with ethyl ether (3 × 50 mL). The organic phase was washed with brine (50 mL), dried on anhydrous Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (DCM / MeOH=20 / 1) on silica gel to obtain tert-butyl(1-(1-(6-(1-acetylazetidine-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate (0.9 g, 5%) as a yellow oily substance. 1H-NMR(300MHz,DMSO-d6)δ[ppm]=9.25(s,1H),8.27(s,1H),7.97(s,1H),7.57(d,J=6.9Hz,1H),5.81-5.75(m,1H),4.55 -4.50(m,1H),4.38-4.34(m,1H),4.27-4.15(m,2H),4.07-4.03(m,1H),1.83(s,3H),1.48(d,J=6.9Hz,3H),1.35(s,9H).

[0189] Step 2: Synthesis of 1-[3-[6-[5-(1-aminoethyl)-1,2,4-triazole-1-yl]pyrimidine-4-yl]azetidine-1-yl]ethanone TFA salt: To a solution of tert-butyl (1-(1-(6-(1-acetylazetidine-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl) carbamate (600 mg, 1.54 mmol, 1 equivalent) in DCM (5 mL), TFA (1 mL) was added at 20-25°C and stirred for 5 hours. The mixture was concentrated to obtain 1-[3-[6-[5-(1-aminoethyl)-1,2,4-triazole-1-yl]pyrimidine-4-yl]azetidine-1-yl]ethanone TFA salt (280 mg, 63%) as a yellow solid. 1 H NMR(400MHz,DMSO-d6)δ[ppm]=9.25(s,1H),8.69(bs,2H),8.48(s,1H),8.00(s,1H),5.54-5.50(m,1H),4.53-4.49(m,1H),4 .34-4.30(m,1H),4.25-4.16(m,2H),4.02-3.99(m,1H),1.80(s,3H),1.64(d,J=6.8Hz,3H).LC-MS(ES)m / z=288.1(M+H-TFA) + .

[0190] Step 3: Synthesis of N-[1-[2-[6-(1-acetylazetidine-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide: 1-[3-[6-[5-(1-aminoethyl)-1,2,4-triazole-1-yl]pyrimidine-4-yl]azetidine-1-yl]ethanone TFA salt (50 mg, 0.125 μmol, 1 equivalent), 3,5-bis(trifluoromethyl)benzoic acid (45 mg, 0.174 mmol, 1.39 equivalents), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium A solution of 3-oxide hexafluorophosphate (86.0 mg, 226 μmol, 1.81 equivalents) and N-ethyl-N-isopropyl-propan-2-amine (0.07 mL, 56.2 mg, 435 μmol, 3.48 equivalents) was stirred at 20-25°C for 20 hours. The solvent was removed under reduced pressure, the residue was dissolved in CH2Cl2 (40 mL), washed with H2O (15 mL), dried on MgSO4, and filtered. The solvent was removed under reduced pressure, and the crude product was purified by column chromatography on silica gel (c-hexane:siRNA=100:0~0:100) to obtain N-[1-[2-[6-(1-acetylazetidine-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (39 mg, 74 μmol, 59%). 1 H NMR(400MHz,CDCl3)δ[ppm]=9.21-9.17(m,1H),8.31-8.27(m,2H),8.02-7.96(m,3H),7.88(dd,J=7.6,0.8Hz,1H),6.57-6.4 9(m,1H),4.57-4.46(m,2H),4.45-4.39(m,1H),4.28-4.22(m,1H),4.05-3.95(m,1H),1.96-1.91(m,3H),1.77-1.72(m,3H). LCMS: Desired mass: m / z(M+H) + =528.2;Actual mass: m / z=528.0.

[0191] Example 6: 3-Chloro-5-[N'-Methoxy-N,N-dimethylcarbamimidoyl]-N-[1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide (I-17) Step 1: Synthesis of methyl 3-chloro-5-[N'-hydroxycarbamimidoyl]benzoate: To a solution of methyl 3-chloro-5-cyano-benzoate (5 g, 25.6 mmol, 1 equivalent) and hydroxylammonium chloride (2.6 g, 38.3 mmol, 1.5 equivalents) in EtOH (50 mL), triethylamine (3.9 g, 38.3 mmol, 1.5 equivalents) was added at 25 °C. The resulting mixture was stirred for 3 hours, at which point completion was determined by TLC (PE: Depositphotos = 5:1). The reaction mixture was quenched with water (50 mL), extracted with Depositphotos (3 × 30 mL), washed with brine (50 mL), dried over Na₂SO₄, and concentrated. The residue was purified by column chromatography on silica gel (PE = 0-30% in Â) to obtain methyl 3-chloro-5-[N'-hydroxycarbamimidoyl]benzoate (5.23 g, 90%) as a yellow solid. 1 H NMR(400MHz,DMSO-d6)δ[ppm]=9.95(s,1H)8.24-8.27(m,1H)7.98(t,J=1.69Hz,1H)7.91(t,J=1.63Hz,1H)6.05(bs,2H)3.89(s,3H).

[0192] Step 2: Synthesis of methyl 3-chloro-5-[N'-methoxycarbamimidoyl]benzoate: To a solution of methyl 3-chloro-5-[N'-hydroxycarbamimidoyl]benzoate (8.2 g, 36 mmol, 1 equivalent) in DMSO / dioxane (20 mL / 100 mL), dimethyl sulfate (6.8 g, 54 mmol, 1.5 equivalents) was added at 0°C. A solution of LiOH×H2O (2.3 g, 54 mmol, 1.5 equivalents) in H2O (9.8 mL) was added dropwise to the reaction mixture at 0°C, and the mixture was heated to 20-25°C with stirring for 5 hours, at which point completion was determined. TLC (PE:HCl = 5:1). The reaction mixture was poured into water (400 mL) and extracted with HCl (3 x 200 ml). The organic layer was washed with brine (500 mL), dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel (PE in  = 0-25%) to obtain methyl 3-chloro-5-[N'-methoxycarbamimidoyl]benzoate (4.5 g, 51%) as a white solid. 1 H NMR(400MHz,DMSO-d6)δ[ppm]=8.22(t,J=1.44Hz,1H)7.98(t,J=1.75Hz,1H)7.93(t,J=1.69Hz,1H)6.31(bs,2H)3.89(s,3H)3.77(s,3H).

[0193] Step 3: Synthesis of methyl 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]benzoate: The reaction was carried out in two parallel batches. To a solution of methyl 3-chloro-5-[N'-methoxycarbamimidoyl]benzoate (2 g, 8.23 ​​mmol, 1 equivalent) and (HCHO)3 (7.4 g, 82.3 mmol, 10 equivalents) in DCE (20 mL), TFA (4.9 g, 41.1 mmol, 5 equivalents) was added, and the mixture was stirred at 80°C for 2 hours. Next, Et3SiH (2.9 g, 24.7 mmol, 3 equivalents) was added dropwise at 80°C, and the mixture was stirred for 16 hours, at which point completion was determined by TLC (PE:siRNA = 10:1). The two batches were combined. The reaction mixture was poured into water (150 mL), extracted with DCM (50 mL x 3), washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (PE in  = 0-25%) to obtain methyl 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]benzoate (2 g, 45%) as a yellow oil. 1 H NMR(400MHz,CDCl3)δ[ppm]=8.06(t,J=1.75Hz,1H)7.88(t,J=1.44Hz,1H)7.46-7.53(m,1H)3.94(s,3H)3.68(s,3H)2.74(s,6H).

[0194] Step 4: Synthesis of 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]benzoic acid: To a solution of methyl 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]benzoate (2.2 g, 8.15 mmol, 1 equivalent) in THF / H2O (20 mL / 4 mL), LiOH × H2O (684 mg, 16.29 mmol, 2 equivalents) was added at 0°C. The mixture was heated to 20-25°C with stirring over 4 hours, and completion was determined at that point by TLC (PE:HCl = 10:1). The reaction mixture was poured into water (50 mL) and extracted with HCl (20 mL). The aqueous layer was adjusted to pH 3 and extracted with HCl (3 × 20 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated to obtain 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]benzoic acid (1.45 g, 70%) as a white solid. 1 H NMR(400MHz,DMSO-d6)δ[ppm]=7.93(s,1H)7.68(s,1H)7.57(s,1H)3.53(s,3H)2.61(s,6H).LCMS: Desired mass: m / z(MH) - =255.1;Actual mass: m / z=255.0.

[0195] Step 5: Synthesis of tert-butyl(1-(1-(6-(oxetan-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate: tert-butyl N-[1-[2-(6-chloropyrimidine-4-yl)-1,2,4-triazole-3-yl]ethyl]carbamate (10.0 g, 30.8 mmol, 1 equivalent), oxetan-3-carboxylic acid (4.72 g, 46.2 mmol, 1.5 equivalents), 2,2 A mixture of '-bipyridine 4,4'-bis(1,1-dimethylethyl) (1.24 g, 4.6 mmol, 0.15 equivalents), dichloro(1,2-dimethoxyethane)nickel (0.68 g, 3.1 mmol, 0.1 equivalent), Cs2CO3 (15.05 g, 46.2 mmol, 1.5 equivalents), and [Ir{dF(CF3)ppy}2(dtbpy)]PF6 (1.04 g, 0.9 mmol, 0.03 equivalents) was stirred under nitrogen at 20-25°C overnight while being irradiated with 450 nm (LED). The reaction mixture was diluted with water (50 mL) and extracted with Et2O (3 × 350 mL). The organic phase was washed with brine (50 mL), dried on anhydrous Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (DCM / MeOH=20 / 1) on silica gel to obtain tert-butyl(1-(1-(6-(oxetan-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate (1.1 g, 7%) as a yellow oily substance. 1 H-NMR(300MHz,DMSO-d6)δ9.25(s,1H),8.26(s,1H),7.92(s,1H),7.58(d,J=7.5Hz,1H),5.81-5.76( m,1H),4.98-4.93(m,2H),4.86-4.82(m,2H),4.62-4.60(m,1H),1.47(d,J=6.9Hz,3H),1.34(s,9H).

[0196] Step 6: Synthesis of 1-(1-(6-(oxetan-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethane-1-ammonium trifluoroacetate: To a solution of tert-butyl(1-(1-(6-(oxetan-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethyl)carbamate (550 mg, 1.60 mmol, 1 equivalent) in DCM (6 mL), TFA (2 mL) was added at 20-25°C, and the resulting mixture was stirred at 20-25°C for 5 hours. Volatile substances were removed under reduced pressure to obtain 1-(1-(6-(oxetan-3-yl)pyrimidine-4-yl)-1H-1,2,4-triazole-5-yl)ethane-1-ammonium trifluoroacetate (270 mg, 69%) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=9.26(d,J=0.8Hz,1H),8.60(bs,2H),8.48(s,1H),7.96(d,J=0.8Hz,1H),5.54-5.49( m,1H),4.96-4.93(m,2H),4.82-4.79(m,2H),4.64-4.56(m,1H),1.64(d,J=6.8Hz,3H).LC-MS(ES)m / z=247.1(M+H-TFA) + .

[0197] Step 7: Synthesis of 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]-N-[1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide: 1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethylammonium trifluoroacetate (50 mg, 139 μmol, 1 equivalent) in DMF (2 mL), 3- A solution of chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]benzoic acid (35.6 mg, 139 μmol, 1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (68.6 mg, 180 μmol, 1.3 equivalents), and diisopropylethylamine (59 μL, 44.8 mg, 347 μmol, 2.5 equivalents) was stirred at 20-25°C for 20 hours. Volatile substances were removed under reduced pressure, and the residue was dissolved in CH2Cl2 (40 mL). The solution was washed with H2O (15 mL), dried over MgSO4, and filtered. The solvent was removed under reduced pressure, and the residue was purified by column chromatography (c-hexane:siRNA=100:0~0:100) on silica gel to obtain 3-chloro-5-[N'-methoxy-N,N-dimethylcarbamimidoyl]-N-[1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]benzamide (55 mg, 0.113 mmol, 82%). 1 H-NMR(400MHz,CDCl3)δ[ppm]=9.21(d,J=1.2Hz,1H),8.00(s,1H),7.91(d,J=1.2Hz ,1H),7.83(t,J=1.9Hz,1H),7.62(t,J=1.5Hz,1H),7.49-7.44(m,1H),7.42(d,J=8.2 Hz,1H),6.55-6.42(m,1H),5.10(dd,J=8.4,6.0Hz,2H),4.98(td,J=6.3,2.3Hz,2H), 4.44(ddd,J=14.8,8.4,6.5Hz,1H),3.66(s,3H),2.68(s,6H),1.71(d,J=6.7Hz,3H). LCMS: Desired mass: m / z(M+H) + =485.2;Actual mass: m / z=485.0.

[0198] Example 7: 3-Chloro-N-[1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-5-(4-pyridylsulfonyl)benzamide(I-18) Step 1: Synthesis of 3-chloro-5-(4-pyridylsulfanyl)benzonitrile: To a solution of 3-chloro-5-fluorobenzonitrile (4 g, 25.6 mmol, 1 equivalent) in DMF (60 mL), pyridine-4-thiol (3.13 g, 28.2 mmol, 1.1 equivalent) and Cs2CO3 (12.5 g, 38.5 mmol, 1.5 equivalent) were added at 25°C. The mixture was stirred at 80°C for 2 hours, at which point completion was determined by TLC (PE:Â=5:1). The reaction mixture was poured into H2O (100 mL), extracted with Â(2 × 100 mL), washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (0% to 20% Â in PE) to obtain 3-chloro-5-(4-pyridylsulfanil)benzonitrile (3.3 g, 52%) as a yellow solid. 1 H-NMR(400MHz, CDCl3)δ[ppm]=8.51(d,J=6.00Hz,2H)7.63-7.73(m,3H)7.06-7.14(m,2H).

[0199] Step 2: Synthesis of 3-chloro-5-(4-pyridylsulfonyl)benzonitrile: In a solution of 3-chloro-5-(4-pyridylsulfanyl)benzonitrile (3.2 g, 13.0 mmol, 1 equivalent) in EtOH (80 mL), add (NH4)6Mo7O at 25°C. 24 .4H2O (7.56 g, 6.5 mmol, 0.5 equivalents) and H2O2 (30%, 2.95 g, 26.0 mmol, 2 equivalents) were added, and the mixture was stirred for 16 hours. At this point, completion was determined by TLC (PE:siRNA = 1:1). The reaction mixture was poured into H2O (200 mL), extracted with siRNA (2 × 100 mL), washed with brine (100 mL), dried on Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (siRNA in PE = 0%~50%) to obtain 3-chloro-5-(4-pyridylsulfonyl)benzonitrile (1.7 g, 47%) as a yellow solid. 1 H-NMR(400MHz,CDCl3)δ[ppm]=8.91-8.97(m,2H)8.14(dt,J=12.1,1.63Hz,2H)7.85-7.90(m,1H)7.76-7.83(m,2H).

[0200] Step 3: Synthesis of 3-chloro-5-(4-pyridylsulfonyl)benzoic acid: The reaction was carried out in two parallel batches. A solution of 3-chloro-5-(4-pyridylsulfonyl)benzonitrile (1.35 g, 4.85 mmol, 1 equivalent) in 75% H2SO4 (15 mL) was stirred at 100°C for 12 hours, at which point completion was determined by TLC (PE:HCl = 1:1). The two batches were combined and quenched with cold water (150 mL). After adjusting the pH to 4-5 with 2N HCl aqueous solution, the mixture was extracted with HCl (3 × 100 mL), washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated to obtain 3-chloro-5-(4-pyridylsulfonyl)benzoic acid (total 2.65 g, 92%) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ[ppm]=8.89-8.93(m,2H)8.40(t,J=1.88Hz,1H)8.35(t,J=1.50Hz,1H)8.20-8.23(m,1H)8.02-8.05(m,2H). LCMS: Desired mass: m / z (MH) - =296.0;Actual mass: m / z=296.0

[0201] Step 4: Synthesis of 3-chloro-N-[1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-5-(4-pyridylsulfonyl)benzamide: 1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethylammonium trifluoroacetate (50 mg, 139 μmol, 1 equivalent) in DMF (2 mL), 3 A solution of chloro-5-(4-pyridylsulfonyl)benzoic acid (41.3 mg, 139 μmol, 1 equivalent), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (68.6 mg, 180 μmol, 1.3 equivalents), and diisopropylethylamine (59 μL, 44.8 mg, 347 μmol, 2.5 equivalents) was stirred at 20-25°C for 20 hours. The solvent was removed under reduced pressure, the residue was dissolved in CH2Cl2 (40 mL), washed with H2O (15 mL), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica gel (c-hexane:siRNA = 100:0~0:100) to obtain 3-chloro-N-[1-[2-[6-(oxetan-3-yl)pyrimidine-4-yl]-1,2,4-triazole-3-yl]ethyl]-5-(4-pyridylsulfonyl)benzamide (60 mg, 114 μmol, 82%). 1 H-NMR(400MHz, CDCl3)δ[ppm]=9.22(d,J=1.2Hz,1H),8.90-8.85(m,2H),8.26 (t,J=1.6Hz,1H),8.04(d,J=1.7Hz,2H),8.00(s,1H),7.92(d,J=1.2Hz,1H),7. 80-7.76(m,2H),7.61(d,J=7.6Hz,1H),6.54-6.44(m,1H),5.11(dd,J=8.4,6.1 Hz,2H),4.98(td,J=6.3,2.2Hz,2H),4.50-4.38(m,1H),1.72(d,J=6.8Hz,3H). LCMS: Desired mass: m / z(M+H) + =485.2;Actual mass: m / z=485.0.

[0202] [Table 4]

[0203] [Table 5]

[0204] [Table 6]

[0205] B. Biological Examples Unless otherwise specified, the test solutions are prepared as follows:

[0206] Dissolve the active compound in a 1:1 (vol:vol) mixture of distilled water and acetone to the desired concentration. Prepare this test solution on the day of use.

[0207] The activity of the compound of formula I of the present invention can be demonstrated and evaluated in the following biological tests.

[0208] B.1 Tobacco budworm (Heliothis virescens) To evaluate the control of Heliothis virescens, a test unit is constructed from a 96-well microtiter plate containing insect bait and 15-25 H. virescens eggs.

[0209] The compound is formulated using a solution containing 75% v / v water and 25% v / v DMSO. 10 μL of the formulated compound at various concentrations is sprayed onto insect feed in two repeated applications using a custom-made microatomizer.

[0210] After application, the microtiter plates are incubated at approximately 28±1°C and approximately 80±5% relative humidity for 5 days. Next, the mortality rates of eggs and larvae are visually assessed.

[0211] In this study, compounds I-1, I-2, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-14, I-15, I-16, I-20, I-21, I-23, I-24, I-26, I-27, I-29, I-30, I-32, I-34, I-39, I-40, I-41, I-42, and I-44 each showed at least a 75% mortality rate compared to the untreated control at 2500 ppm.

[0212] B.2 Boll weevil (Anthonomus grandis) To evaluate the control of the water hyacinth weevil (Anthonomus grandis), a test unit is constructed from a 96-well microtiter plate containing insect bait and 5-10 A. grandis eggs.

[0213] The compound is formulated using a solution containing 75% v / v water and 25% v / v DMSO. Using a custom-made microatomizer, 5 μL of the formulated compound at various concentrations is sprayed onto insect feed in two repeated applications.

[0214] After application, the microtiter plates are incubated at approximately 25±1°C and approximately 75±5% relative humidity for 5 days. Next, the mortality rates of eggs and larvae are visually assessed.

[0215] In this study, compounds I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16, I-19, I-20, I-21, I-23, I-24, I-25, I-26, I-27, I-28, I-29, I-30, I-31, I-32, I-34, I-35, I-37, I-38, I-39, I-40, I-41, I-42, I-43, and I-44 each showed at least a 75% mortality rate compared to the untreated control at 2500 ppm.

[0216] B.3 Southern armyworm (Spodoptera eridania), 2nd instar larva The active compound is formulated in 100% cyclohexanone as a 10,000 ppm solution supplied in a tube by a Tecan liquid handler. Intermediate solutions are prepared by serially diluting the 10,000 ppm solution with 100% cyclohexanone. These serve as stock solutions, which are then subjected to a final dilution of 50% acetone:50% water (v / v) by Tecan and placed in 10 or 20 ml glass vials. 0.01% (v / v) of a nonionic surfactant (Kinetic®) is added to this solution. The vial is then inserted into an automatic electrostatic sprayer equipped with a spray nozzle for application to plants / insects. Two lima bean plants (Sieva variety) are grown in pots and selected for treatment at the first true leaf stage. The test solution is sprayed onto the leaves using an automatic electrostatic plant sprayer equipped with a spray nozzle. The plants are dried in the sprayer's fume hood and then removed from the sprayer. Place each pot in a perforated plastic bag with a zipper. Place 10-11 armyworm larvae into the bag and close the zipper. Maintain the test plants for 4 days in a growing room at approximately 25°C and 20-40% relative humidity, avoiding direct exposure to fluorescent lighting (14:10 light:dark light cycle) to prevent them from being trapped by the heat inside the bag. After 4 days, evaluate the mortality rate and reduction in food intake compared to untreated control plants.

[0217] In this study, compounds I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-14, I-15, and I-16 each showed at least a 75% mortality rate compared to the untreated control at 300 ppm.

[0218] B.4 Aedes aegypti (Yellow fever mosquito) To evaluate the control of yellow fever mosquitoes (Aedes aegypti), the test unit will consist of a 96-well microtiter plate containing 200 μl of tap water per well and 5 to 15 newly hatched Aedes aegypti larvae.

[0219] The active compound is formulated using a solution containing 75% (v / v) water and 25% (v / v) DMSO. 2.5 μL of the formulated compound or mixture at various concentrations is sprayed onto insect feed in two repeated applications using a custom-made microatomizer.

[0220] After application, the microtiter plates are incubated at 28±1°C and 80±5%RH for 2 days. Then, the larval mortality rate is visually assessed.

[0221] In this study, compounds I-1, I-2, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-14, I-15, I-16, I-19, I-20, I-21, I-23, I-26, I-27, I-28, I-29, I-30, I-31, I-32, I-34, I-35, I-37, I-38, I-39, I-40, I-41, I-42, I-43, and I-44 each showed at least a 75% mortality rate compared to the untreated control at 2500 ppm.

[0222] B.5 Green peach aphid (Myzus persicae) To evaluate the control of the green peach aphid (Myzus persicae) through systemic means, a test unit was constructed from a 96-well microtiter plate containing liquid artificial feed under an artificial membrane.

[0223] The compound was formulated using a solution containing 75% v / v water and 25% v / v DMSO. Using a custom-made pipette, the formulated compound at various concentrations was transferred to aphid feed in two replicates.

[0224] After application, 5-8 adult aphids were placed on an artificial membrane in a microtiter plate well. The aphids were then allowed to feed on the treated aphid food and incubated for 3 days at approximately 23±1°C and approximately 50±5% relative humidity. Subsequently, aphid mortality and reproduction were visually evaluated.

[0225] In this study, compounds I-1, I-2, I-4, I-6, I-7, I-8, I-9, I-11, I-12, I-14, I-15, I-16, I-17, I-19, I-20, I-21, I-22, I-23, I-24, I-25, I-26, I-29, I-31, I-34, I-35, I-38, I-43, and I-44 each showed a mortality rate of at least 75% compared to the untreated control at 2500 ppm.

[0226] Comparison of activity with conventional technology The beneficial activity of the compound according to the present invention, which contains a 6-substituted 4-pyrimidinyl ring, against structurally similar compounds known from the prior art that differ in the 6-membered hetalil moiety attached to the 1,2,4-triazole was demonstrated by the following comparative experiments:

[0227] The table below shows the mortality rate compared to an untreated control group.

[0228] [Table 7]

Claims

1. Equation I 【Chemistry 1】 (In the formula, R １ is H, OH, NR １２ R １３ , C １ -C ６ -alkyl, C １ -C ６ -haloalkyl, C ３ -C ６ -cycloalkyl, C ３ -C ６ -halocycloalkyl, C １ -C ５ -alkoxy, C １ -C ４ -alkyl-C ３ -C ６ -cycloalkyl, C １ -C ４ -alkyl-C ３ -C ６ -halocycloalkyl, C ３ -C ６ -alkenyl, C ３ -C ６ -alkynyl (the group is unsubstituted or partially or fully substituted by R １１ ); or C(=N-R) １１ ) R １２ , C(O)R １１ａ And; R １０ H, C １ -C ４ - Alkyl, C １ -C ４ - Haloalkyl, C ３ -C ６ - Cycloalkyl, C ３ -C ６ - Halocycloalkyl, C ３ -C ４ -Cycloalkyl C １ -C ２ - Alkyl, C ３ -C ４ -Halocycloalkyl-C １ -C ２ -Alkyl, C(O)-C １ -C ４ -Alkyl, C(O)-C １ -C ４ -Haloalkyl, C(O)-C ３ -C ４ -Cycloalkyl, C(O)-C ３ -C ４ - Halocycloalkyl, SO ｍ -C １ -C ４ - Alkyl, SO ｍ -C １ -C ４ - Haloalkyl, SO ｍ -C ３ -C ６ -Cycloalkyl, or phenyl (unsubstituted or R ３ａ (Partially or completely replaced by; R １１ is halogen, CN, NO ２ , NR １２ R １３ , C(O)NH ２ , C(S)NH ２ , C(O)OH, OR １０ , Si(CH ３ ) ３ ; C １ -C ６ -alkyl; C １ -C ６ -haloalkyl; C ２ -C ６ -alkenyl; C ２ -C ６ -haloalkenyl; C ２ -C ６ -alkynyl; C ２ -C ６ -haloalkynyl; C ３ -C ４ -cycloalkyl-C １ -C ２ -alkyl (the ring is unsubstituted or substituted with one or two halogens); 3-6 membered heterocyclyl, 5- or 6-membered heteroaryl or phenyl (the ring is unsubstituted or substituted with halogen, C １ -C ３ -haloalkyl and / or CN); R １１ａ is NR １２ R １３ 、C(O)NH ２ 、C(S)NH ２ 、C(O)OH, OR １０ 、Si(CH ３ ) ３ ; C １ -C ６ - haloalkyl; C ２ -C ６ - alkenyl; C ２ -C ６ - haloalkenyl; C ２ -C ６ - alkynyl; C ２ -C ６ - haloalkynyl; C ３ -C ４ - cycloalkyl - C １ -C ２ - alkyl (the ring is unsubstituted or substituted with one or two halogens); 3 - 6 membered heterocyclyl (the ring is unsubstituted or substituted with halogen, C １ -C ３ - haloalkyl and / or CN); R １２ , R １３ H and C are independent of each other. １ -C ４ - Alkyl, C １ -C ４ - Alkoxy, C １ -C ４ - Haloalkoxy, C １ -C ４ - Haloalkyl, C ３ -C ６ -Cycloalkyl, C(O)-C １ -C ４ -Alkyl, C(O)-C １ -C ４ -Haloalkyl, C(O)-C ３ -C ４ -Cycloalkyl, C(O)-C ３ -C ４ - Halocycloalkyl, C(O)NH-C １ -C ４ -Alkyl, C(O)NH-C １ -C ４ - Haloalkyl, C(O)N(C １ -C ４ -Alkyl)-C ４ -C ４ - Alkyl, C(O)N(C １ -C １ -Haloalkyl)-C １ -C １ - Alkyl, C(O)N(C １ -C ４ -Haloalkyl)-C ４ -C ４ -Haloalkyl, C(O)NH-C １ -C ４ -alkoxy, C(O)NH-C １ -C ４ - Haloalkoxy, C(O)NH-C １ -C ４ -Alkoxy-C １ -C ４ -Alkyl, C(O)NH-C １ -C ４ -Alkoxy-C １ -C ４ - Haloalkyl; C(O)NH-phenyl, C(O)NH-3- to 6-membered heterocyclyl or 5- or 6-membered hetalyl, C(O)NH-C １ -C ４ -Alkyl-phenyl, C(O)NH-C １ -C ４ -Alkyl-3- to 6-membered heterocyclyl or 5- or 6-membered heterocyclyl (the ring is unsubstituted or contains halogen, C) １ -C ４ - Haloalkyl and / or CN; S(O) ｍ -C １ -C ４ - Haloalkyl, S(O) ｍ -C ３ -C ４ - Cycloalkyl, S(O) ｍ -C ３ -C ４ - Halocycloalkyl; 3- to 6-membered heterocyclyl, 5- or 6-membered heterocyclyl, or phenyl (these rings are unsubstituted or halogen, C) １ -C ３ (substituted with haloalkyl and / or CN); or R １２ and R １３ Together with the nitrogen atoms to which they are bonded, they form 3-, 4-, 5-, 6-, or 7-membered saturated, partially unsaturated, or fully unsaturated heterocycles, the heterocycles having N, O, and S(O) as ring members. ｍ and may further contain one or two heteroatoms or heteroatom-containing groups optionally selected from one or two C(O) groups, the heterocycle being unsubstituted or containing one or more R ３ａ Replaced; m is 0, 1, or 2; R ２ H, CN, C １ -C ３ - Alkyl, C １ -C ３ - Haloalkyl, C ２ -C ３ - It is alkinyl; R ３ These are halogens, CN, NO ２ ; C １ -C ４ - Alkyl, C ３ -C ６ - Cycloalkyl, C １ -C ６ - Haloalkyl, C １ -C ６ - Halocycloalkyl, C １ -C ６ - Alkenil, C １ -C ６ - Alkinyl, C ３ -C ６ -Cycloalkyl-C １ -C ６ - Alkyl, C １ -C ６ -Alkyl-C ３ -C ６ -Cycloalkyl (these are unsubstituted or R ３ａ (It is replaced by) OR １４ , NR １２ R １３ , C(O)NR １２ R １３ , C(O)OR １４ , C(O)R １５ , S(O) ｍ -R １５ And; R １４ R １０ As defined for; R １５ H, C １ -C ４ - Alkyl or C １ -C ４ - Haloalkyl, C ３ -C ６ - Cycloalkyl, C １ -C ６ - Halocycloalkyl (carbon chain is unsubstituted or R １１ (partially or completely substituted); or 3- to 6-membered heterocyclyl, 5- or 6-membered heterocyclyl or phenyl (the ring is unsubstituted or R ３ａ (It is replaced by; R ３ａ These are halogens, CN, NO ２ OH, C １ -C ４ - Alkyl, C １ -C ４ - Haloalkyl, C １ -C ４ -Alkoxy-C １ -C ４ - Alkyl, C １ -C ４ - Haloalkoxy, C ３ -C ４ - Cycloalkyl, C ３ -C ４ - Halocycloalkyl, S(O) ｍ -C １ -C ４ - Alkyl, S(O) ｍ -C １ -C ４ - Haloalkyl, S(O) ｍ -C ３ -C ４ - Cycloalkyl, S(O) ｍ -C ３ -C ４ -It is a halocycloalkyl; n is 0, 1, 2, or 3; R ４ is a 5-membered or 6-membered hetalyl, or phenyl (the ring is unsubstituted or R ３ (It is replaced by) or R ４ is N, O, S(O) ｍ A 3- to 7-membered saturated or unsaturated heterocycline containing at least one heteroatom or group selected from and optionally one or two C(O) groups as ring members (this heterocycline is either unsubstituted or substituted with a ring C atom, R ３ If R is partially or completely substituted; or substituted with a ring N atom, ３ｂ (It is partially or completely replaced by:) R ３ｂ C １ -C ４ - Alkyl, C ３ -C ６ - Cycloalkyl, C １ -C ６ - Haloalkyl, C １ -C ６ - Halocycloalkyl, C １ -C ６ - Alkenil, C １ -C ６ - Alkinyl, C ３ -C ６ -Cycloalkyl-C １ -C ６ - Alkyl, C １ -C ６ -Alkyl-C ３ -C ６ -Cycloalkyl (these are unsubstituted or R ３ａ (Substituted with); C(O)NR １２ R １３ , C(O)OR １４ , C(O)R １５ , S(O) ｍ -R １５ And; R ５ R ３ As defined for; X is N, CH, or CR ３ｃ And; R ３ｃ R ３ Compounds of (as defined for); as well as their N-oxides, stereoisomers, and agriculturally or veterinarily acceptable salts.

2. R １ However, H or CH ２ -cc ３ H ５ The compound of formula I as described in claim 1.

3. R ２ CH ３ The compound of formula I according to claim 1 or 2.

4. R ３ However, halogen, CN, C １ -C ４ - Haloalkyl, C １ -C ４ - Haloalkoxy, C ３ -C ４ -Cycloalkyl (unsubstituted or substituted with one or more CN or halogens), C ３ -C ４ - Halocycloalkyl, S(O) ｍ -C １ -C ４ - Alkyl, S(O) ｍ -C １ -C ４ - Haloalkyl, S(O) ｍ - (R １１ A compound of formula I according to any one of claims 1 to 3, which is a phenyl partially substituted with phenyl.

5. n is 2, R ３ A compound of formula I according to any one of claims 1 to 4, wherein the 3rd and 5th positions are located.

6. A compound of formula I according to any one of claims 1 to 5, wherein X is CH.

7. R ４ However, 2-pyridinyl, 3-pyridinyl, 2-thiazolyl, 1-pyrazolyl, 3-thietanyl, 3-(1-oxo-thietanyl), 3-(1,1-dioxo-thietanyl), or 3-azetidinyl (R ３ A compound of formula I according to any one of claims 1 to 6, wherein the compound is substituted with (the compound being substituted with).

8. R ４ is phenyl or hetalil, and (R ３ ) ｎ at least one R inside ３ The base is R ３ｄ Selected from, R ３ｄ However, C ３ -C ６ - Cycloalkyl, C ３ -C ６ - Halocycloalkyl, C ２ -C ６ - Alkenil, C ２ -C ６ - Alkinyl, C ３ -C ６ -Cycloalkyl-C １ -C ６ - Alkyl, C １ -C-alkyl-C ３ -C ６ -Cycloalkyl (these are unsubstituted or R ３ａ (Replaced by); NR １２ R １３ , C(O)NR １２ R １３ , C(O)OR １４ , C(O)R １５ , and S(O) ｍ -R １５ A compound of formula I according to any one of claims 1 to 7, wherein m is 1 or 2.

9. R ５ However, H or cC ３ H ５ A compound of formula I according to any one of claims 1 to 8.

10. Mainly isomer I.S. 【Chemistry 2】 A compound of formula I according to any one of claims 1 to 9, comprising the above.

11. An agricultural or veterinary composition comprising at least one compound and / or at least one agriculturally or veterinarily acceptable salt thereof according to any one of claims 1 to 10, and at least one inert liquid and / or solid agriculturally or veterinarily acceptable carrier.

12. An agricultural composition for controlling animal pests, comprising at least one compound according to any one of claims 1 to 10, at least one acceptable inert liquid and / or solid carrier, and optionally at least one surfactant.

13. A method for eradicating or controlling invertebrate pests, comprising contacting the pest or its food source, habitat or breeding ground with at least one compound described in any one of claims 1 to 10 in an effective amount for killing the pest.

14. A method for protecting a growing plant from attack or parasitism by an invertebrate pest, comprising contacting the plant or the soil or water in which the plant is growing with an effective amount of at least one compound according to any one of claims 1 to 10.

15. Seeds containing a compound according to any one of claims 1 to 10, or an enantiomer, diastereomer, or salt thereof, in an amount of 0.1 g to 10 kg per 100 kg of seeds.

16. A method for treating or defending an animal against parasitism or infection by an invertebrate pest, comprising contacting the animal with an effective amount of at least one compound of formula I described in any one of claims 1 to 10, a stereoisomer thereof, and / or at least one veterinarily acceptable salt thereof.

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