Microbicidal pyrazole derivatives

Abstract

A compound of formula (I) - wherein the substituents are as defined in claim 1 - and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers, and N-oxides of those compounds, which can be used as fungicides. (I)

Description

[0001] This invention relates to novel antimicrobial pyrazole derivatives, for example, as active ingredients, which possess antimicrobial activity, particularly antifungal activity. The invention also relates to the preparation of these pyrazole derivatives, to intermediates useful in the preparation of these pyrazole derivatives, to the preparation of these intermediates, to agricultural chemical compositions comprising at least one of these pyrazole derivatives, to the preparation of these compositions, and to the use of these pyrazole derivatives or compositions in agriculture or horticulture for controlling or preventing infection of plants, harvested food crops, seeds, or inanimate materials by plant pathogenic microorganisms, particularly fungi. Antimicrobial pyrazole derivatives were previously disclosed in WO 2023 / 012044.

[0002] According to a first aspect of the invention, a compound having formula (I) is provided:

[0003] (I)

[0004] in

[0005] R 1 Selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl;

[0006] R 2 Selected from hydrogen, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbonimide, N-hydroxy-C-C1-C4-alkyl-carbonimide, or C1-C4-alkoxycarbonyl;

[0007] R 3 Selected from hydrogen, halogens, or C1-C4-alkyl groups;

[0008] R 4 Selected from hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or N,N-di(C1-C4alkyl)aminocarbonyl;

[0009] R 5 and R 6 Independently selected from hydrogen or C1-C4-alkyl;

[0010] A 1 Selected from CR 7 Or N,

[0011] A 2 Selected from CR 8 Or N;

[0012] A 3 Selected from CR 9 Or N;

[0013] R 7 R 8 R 9 It is independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, or C1-C4-haloalkyl;

[0014] B 1 B 2 B 3 Independently selected from CR 10 , N, NR 11 O, or S, provided that B is a valid choice. 1 B 2 B 3 No more than one of them is O or S;

[0015] R 10 Selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-enoxy, C2-C4-alkynoxy, C1-C4-alkylthioalkyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1- C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, hydroxy, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms individually selected from N, O or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy;

[0016] R 11 Selected from hydrogen or C1-C4-alkyl; and

[0017] Z 1The group is selected from C1-C4 alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl groups contains 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl groups is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthioalkyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, or C2-C4-alkynyl;

[0018] Or its agriculturally chemically acceptable salt, stereoisomer, enantiomer, tautomer, or N-oxide.

[0019] Surprisingly, it has been found that compounds of formula (I) have very favorable levels of bioactivity for protecting plants against fungal diseases for practical purposes.

[0020] According to a second aspect of the invention, an agricultural chemical composition comprising an effective amount of the compound of formula (I) according to the invention is provided. This agricultural composition may further comprise at least one additional active ingredient and / or an agriculturally chemically acceptable diluent or carrier.

[0021] According to a third aspect of the invention, a method for controlling or preventing the infection of useful plants by plant pathogenic microorganisms is provided, wherein a fungicide effective amount of a compound of formula (I) according to the invention, or a composition comprising a compound of formula (I), is applied to the plants, parts thereof, or sites thereof.

[0022] According to a fourth aspect of the invention, the use of a compound having formula (I) according to the invention is provided as a fungicide. According to this particular aspect of the invention, this use may exclude methods of treating a human or animal body by surgery or therapy, and diagnostic methods performed on a human or animal body.

[0023] Compounds having at least one basic center and having formula (I) can form, for example, acid addition salts with: strong inorganic acids (such as mineral acids, such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid, or hydrohalic acid), strong organic carboxylic acids (such as unsubstituted or, for example, halogenated C1-C4 alkylcarboxylic acids, such as acetic acid, saturated or unsaturated dicarboxylic acids, such as oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid, or phthalic acid, such as hydroxycarboxylic acids, such as ascorbic acid, lactic acid, malic acid, tartaric acid, or citric acid, or such as benzoic acid), or organic sulfonic acids (such as unsubstituted or, for example, halogenated C1-C4 alkylsulfonic acids or arylsulfonic acids, such as methanesulfonic acid or p-toluenesulfonic acid). A compound having at least one acidic group of formula (I) may, for example, form a salt with a base, such as a mineral salt, like an alkali metal or alkaline earth metal salt, such as a sodium salt, potassium salt or magnesium salt; or form a salt with ammonia or an organic amine (such as morpholine, piperidine, pyrrolidine, mono-, di- or tri-alkylamines, such as ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di- or tri-hydroxyalkylamines, such as monoethanolamine, diethanolamine or triethanolamine).

[0024] In each case, the compound having formula (I) according to the invention is in free form, oxidized form (such as N-oxide), or salt form (e.g., an agronomically available salt form).

[0025] N-oxides are the oxidized forms of tertiary amines or nitrogen-containing heteroaromatic compounds. They are described, for example, in A. Albini and S. Pietra’s book “Heterocyclic N-oxides”, CRC Press, Boca Raton, 1991.

[0026] The compounds of formula (I) according to the invention also include hydrates that may form during salt formation.

[0027] When substituents are indicated as "optionally substituted," this means that they may or may not have one or more of the same or different substituents, for example, one, two, or three R. xSubstituents. For example, C1-C6 alkyl groups substituted with one, two, or three halogens may include, but are not limited to, -CH2Cl, -CHCl2, -CCl3, -CH2F, -CHF2, -CF3, -CH2CF3, or -CF2CH3 groups. As another example, C1-C6 alkoxy groups substituted with one, two, or three halogens may include, but are not limited to, CH2ClO-, CHCl2O-, CCl3O-, CH2FO-, CHF2O-, CF3O-, CF3CH2O-, or CH3CF2O- groups. Further, as used herein, the term "optionally substituted" means that the mentioned group is either unsubstituted or substituted.

[0028] As used herein, the term "halogen" or "halogenated" refers to fluorine (fluoro), chlorine (chloro), bromine (bromo), or iodine (iodo), preferably fluorine, chlorine, or bromine. This also applies accordingly to halogens combined with other meanings, such as halogenated alkyl, halogenated alkenyl, halogenated alkynyl, halogenated alkoxy, and halogenated cycloalkyl.

[0029] As used in this article, amino refers to the -NH2 group.

[0030] As used in this article, cyano refers to the -CN group.

[0031] As used herein, the term "hydroxyl" or "hydroxyl" refers to the -OH group.

[0032] As used in this article, the term "carboxylic acid" refers to the -COOH group.

[0033] As used in this article, the term "C1-C" n "-alkyl" refers to a saturated straight-chain or branched hydrocarbon group having 1 to n carbon atoms attached via any one of the carbon atoms, such as, but not limited to, any one of the following groups: methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, n-pentyl, 1,1-dimethylpropyl, or 1,2-dimethylpropyl.

[0034] As used in this article, the term "C2-C" n "-Alkenyl" refers to a straight-chain or branched alkenyl chain portion having two to n carbon atoms and one or two double bonds, such as vinyl, prop-1-alkenyl, and but-2-alkenyl.

[0035] As used in this article, the term "C2-C" n"-Alynyl" refers to a straight-chain or branched alkynyl chain portion having two to n carbon atoms and a triple bond, such as ethynyl, prop-2-alkynyl, and but-3-alkynyl.

[0036] As used in this article, the term "C3-C" n "-cycloalkyl" refers to tri(3) to n-membered cycloalkyl groups, such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0037] As used in this article, the term "C1-C" n "-alkoxy" refers to a straight-chain or branched saturated alkyl group (as mentioned above) having one (1) to n carbon atoms attached via an oxygen atom, i.e., any one of the following groups, for example: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, and 1,1-dimethylethoxy. As used herein, the term "C2-C" refers to... n "-Alkenyloxy" refers to a straight or branched alkenyl chain with two (2) to n carbon atoms attached via an oxygen atom (as mentioned above).

[0038] As used in this article, the term "C1-C" n -alkoxy-C1-C n "-alkyl" refers to a compound formed by C1-C2. n -Alkoxy-substituted alkyl groups (as mentioned above). Examples are methoxymethyl, methoxyethyl, ethoxymethyl, and propoxymethyl.

[0039] As used in this article, the term "C1-C" n "-Halogenated alkyl" refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to n carbon atoms attached via any one carbon atom, wherein some or all of the hydrogen atoms in these groups may be replaced by fluorine, chlorine, bromine and / or iodine, i.e., for example, but not limited to, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, or 2,2,2-trichloroethyl.

[0040] As used in this article, the term "C1-C" n -alkylthio" or "C1-C n "-Alkenylthioalkyl" refers to a C1-C bonded by sulfur atoms. n -alkyl.

[0041] As used in this article, the term "C1-C" n "-alkylsulfinyl" refers to a C1-C group linked by a sulfur atom through a sulfinyl group (or S(=O)-).n alkyl.

[0042] As used in this article, the term "C1-C" n "-alkylsulfonyl" refers to a C1-C group connected by a sulfur atom through a sulfonyl group (or S(=O)2-). n alkyl.

[0043] As used in this article, the term "C1-C" n "-alkylcarbonyl" refers to a C1-C group linked by a carbonyl (C=O) group. n -alkyl.

[0044] As used in this article, the term "C1-C" n "-alkoxycarbonyl" refers to a C1-C group connected by a carbonyl (or C=O) group. n -alkoxy moiety.

[0045] As used in this article, the term "C1-C" n "-alkylaminocarbonyl" refers to a C1-C group linked by a carbonyl (C=O) carbon atom. n -alkylamino (or R a NHC(=O)-, where R a It is C1-C n -alkyl).

[0046] As used herein, the term "N-C1-C4-alkoxy-C-C1-C4-alkyl-carbonimide" refers to a group having the formula -C(R a )=NO(R b ) groups, wherein R a It is a C1-C4 alkyl group as generally defined above, and R b It is a C1-C4 alkyl group as generally defined above.

[0047] As used herein, the term "N-hydroxy-C-C1-C4-alkyl-carbonimide" refers to a group having the formula -C(R a The group = NOH, where R a It is C as usually defined above. 1- C4 alkyl.

[0048] As used in this article, the term "C1-C" n "-alkylaminocarbonyl" refers to a group with the formula R, where the carbon atom of the carbonyl group (C=O) is linked to the carbonyl group. a The group of NHC(=O)-, where R a It is C1-C as usually defined above. n -alkyl.

[0049] As used in this article, the term "two (C1-C)"n "-alkyl)aminocarbonyl" refers to a group with the formula R, where the carbon atom of the carbonyl group (C=O) is linked to the carbonyl group. a NR b A group of C (=O), where R a It is C as usually defined above. 1- C n Alkyl, and R b It is C as usually defined above. 1- C n alkyl.

[0050] As used in this article, the term "N-C1-C" n "-alkylamino" refers to a compound with the formula -NH-R a The group, wherein R a It is C1-C as defined above. n alkyl.

[0051] As used in this article, the term "N,N-II (C1-C)" n "-alkyl)amino" refers to a compound with the formula -N(R) a )R a The groups, wherein each R a They can be the same or different as defined above, C1-C n alkyl.

[0052] As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic group comprising 1, 2, 3, or 4 heteroatoms individually selected from N, O, or S. Examples of heteroaryl groups include, but are not limited to, furanyl (furanyl or furyl), pyrroleyl, thiopheneyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidinyl, or pyridinyl. n -alkyl" or "heteroaryl-C3-C" n "-cycloalkyl" refers to C1-C1 alkyl groups that are substituted with heteroaryl groups. n -alkyl or C3-C n -Cycloalkyl. Heteroaryl-C1-C n -alkyl or heteroaryl-C3-C n -Cycloalkyl groups can be substituted on heteroaryl, alkyl, and / or cycloalkyl groups when appropriate.

[0053] As used herein, the term “control” means reducing the number of pests, eliminating pests and / or preventing further pest damage, thereby reducing damage to plants or plant-derived products.

[0054] As used herein, the term "pest" refers to insects and mollusks present in the storage of agricultural, horticultural, forestry, and plant-derived products (such as fruits, grains, and timber); as well as pests associated with damage to man-made structures. The term "pest" encompasses all stages of the pest's life cycle.

[0055] As used herein, the term "effective amount" refers to the amount of a compound or its salt that provides the desired effect when applied in a single or multiple applications.

[0056] The effective amount is readily determined by those skilled in the art using known techniques and by observing results obtained under similar conditions. In determining the effective amount, numerous factors are considered, including but not limited to, the type of plant or derivative to be applied; the pest to be controlled and its life cycle; the specific compound applied; the type of application; and other relevant circumstances.

[0057] As used herein, the terms “room temperature” or “RT” or “rt” refer to a temperature of about 15°C to about 35°C. For example, rt can refer to a temperature of about 20°C to about 30°C, or about 25°C.

[0058] The following list provides the substituents R of compounds having formula (I) according to the present invention. 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 A 1 A 2 A 3 B 1 B 2 B 3 and Z 1 The definitions, including preferred definitions, are provided below. For any of these substituents, any definition given below may be combined with any other definition of any substituent given below or elsewhere in this document.

[0059] In one embodiment of the present invention, R 1 Selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl. Preferably, R 1 It is hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl. More preferably, R 1It is a C1-C3-alkyl or C3-C6-cycloalkyl. Even more preferably, R 1 It is methyl, ethyl, or cyclopropyl. Even more preferably, R 1 It is a methyl group.

[0060] In one embodiment of the present invention, R 2 It is hydrogen, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbonimide, N-hydroxy-C-C1-C4-alkyl-carbonimide, or C1-C4-alkoxycarbonyl. Preferably, R 2 It is hydrogen, halogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C3-haloalkyl, C3-C6-cycloalkyl, C1-C2-alkylcarbonyl, N-C1-C2-alkoxy-C-C1-C3-alkyl-carbonimide, N-hydroxy-C-C1-C3-alkyl-carbonimide, or C1-C3-alkoxycarbonyl. More preferably, R 2 It is hydrogen, halogen, C1-C3-alkyl, C3-C4-cycloalkyl, C1-C2-alkylcarbonyl, N-C1-C2-alkoxy-C-C1-C3-alkyl-carbonimide, or N-hydroxy-C-C1-C2-alkyl-carbonimide. Even more preferably, R 2 It is hydrogen, fluorine, chlorine, bromine, methyl, ethyl, cyclopropyl, acetyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, or -C(CH3)=NOH. Even more preferably, R 2 It is hydrogen, fluorine, chlorine, methyl, or cyclopropyl.

[0061] In another embodiment of the invention, R 2 It is hydrogen, halogen, C1-C4-alkyl, or C3-C6-cycloalkyl. Preferably, R 2 It is hydrogen, halogen, C1-C3-alkyl, or cyclopropyl.

[0062] In one embodiment of the present invention, R 3 It is hydrogen, halogen, or C1-C4-alkyl. Preferably, R 3 It is hydrogen, halogen, or C1-C3-alkyl. More preferably, R 3 It is hydrogen, fluorine, chlorine, or methyl. Even more preferably, R 3 It is hydrogen.

[0063] In one embodiment of the present invention, R 4It is hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or N,N-bis(C1-C4alkyl)aminocarbonyl.

[0064] Preferably, R 4 It is hydrogen, halogen, cyano, C1-C3-alkyl, C1-C2-alkylcarbonyl, C1-C2-alkoxycarbonyl, C1-C2-alkylaminocarbonyl, or N,N- Di(C1-C2-alkylamino)carbonyl. More preferably, R 4 It is hydrogen, halogen, cyano, C1-C3-alkyl, or C1-C2-alkoxycarbonyl. Even more preferably, R... 4 It is hydrogen, halogen, cyano, or C1-C3-alkyl. Even more preferably, R 4 It is hydrogen, cyano, or C1-C3-alkyl. Most preferably, R 4 It is either hydrogen or methyl.

[0065] In one embodiment of the present invention, R 5 and R 6 Independently selected from hydrogen or C1-C4-alkyl. Preferably, R 5 and R 6 Independently selected from hydrogen or C1-C3-alkyl. More preferably, R 5 and R 6 Independently selected from hydrogen or methyl. Even more preferably, R 5 and R 6 It is hydrogen.

[0066] In one embodiment of the present invention, A 1 It is CR 7 Or N, A 2 It is CR 8 Or N; and A 3 It is CR 9 Or N. Preferably, A 1 It is CH, C(CH3), or N, A 2 It is CH, C(CH3), or N; and A 3 It is CH, C(CH3), or N. More preferably, A 1 Is it CH or N, A 2 It is CH or N; and A 3 It is CH or N.

[0067] In one embodiment of the present invention, R 7 R 8 R 9 Independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C1-C4-haloalkyl. Preferably, R7 R 8 R 9 Independently selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C1-C3-haloalkyl. More preferably, R 7 R 8 R 9 Independently selected from hydrogen or C1-C3-alkyl. Even more preferably, R 7 R 8 R 9 It is independently selected from hydrogen or methyl. Most preferably, R 7 R 8 R 9 It is hydrogen.

[0068] In one embodiment of the present invention, B 1 B 2 B 3 Independently selected from CR 10 , N, NR 11 O, or S, provided that B is a valid choice. 1 B 2 B 3 No more than one of them is O or S. Preferably, B 1 B 2 B 3 Independently selected from CR 10 N, O, or S, provided that B is a given. 1 B 2 B 3 No more than one of them is O or S.

[0069] In one embodiment of the present invention, R 10 It is hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-enoxy, C2-C4-alkynoxy, C1-C4-alkylthioalkyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, hydroxy, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, 3, or 4 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy. Preferably, R 10 It is hydrogen, halogen, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C2-C4-olefin, C2-C4-alkynoxy, C1-C2-alkylthioalkyl, C1-C2-alkylsulfinyl, C1-C2-alkylsulfonyl, C1-C2-alkoxy-C1-C3-alkyl, NC 1- C2-alkylamino, N,N-di-(C 1- C 42 -alkyl)amino, C1-C2-alkoxycarbonyl, C1-C2-alkylcarbonyl, N-C1-C2-alkoxy-C1-C2-alkyl-carbonimide, N-hydroxy-C1-C2-alkyl-carbonimide, hydroxy, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1 or 2 substituents independently selected from: halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, or C1-C3-alkoxy. More preferably, R 10 It is hydrogen, halogen, cyano, amino, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains one heteroatom selected from N; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, methyl, ethyl, or trifluoromethyl. Even more preferably, R 10It is hydrogen, halogen, cyano, amino, C1-C3-alkoxy, cyclopropyl, phenyl, or a 5-membered heteroaryl; wherein any one of the 5-membered heteroaryl groups contains one heteroatom selected from N; and wherein any one of the phenyl, 5-membered heteroaryl, and cyclopropyl groups is unsubstituted or substituted by one or two substituents independently selected from: fluorine, chlorine, cyano, or methyl.

[0070] In one embodiment of the present invention, R 10 It is R 10a Or R 10b , where R 10a R 10b Independently selected from hydrogen, chlorine, fluorine, bromine, methyl, ethyl, trifluoromethyl, difluoromethyl, difluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, methoxy, ethoxy, propoxy, allyloxy, prop-2-acetyloxy, methoxymethyl, ethoxy-methyl, 2-methoxyethoxymethyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, acetyl, propionyl, -C(CH3)=NOCH3, -C(CH3)=NOCH2CH3, -C(CH3)=NOH, trifluoromethylsulfonyloxy, cyano, amino, carboxyl, phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-methylbenzene The following compounds are used: 3-methylphenyl, 4-methylphenyl, [4-(trifluoromethyl)pyrazole-1-yl], [3-(trifluoromethyl)pyrazole-1-yl], (3-cyanopyrazole-1-yl), (4-cyanopyrazole-1-yl), (5-chloropyrazole-1-yl), (4-chloropyrazole-1-yl), (3-chloropyrazole-1-yl), (5-fluoropyrazole-1-yl), (4-fluoropyrazole-1-yl), (3-fluoropyrazole-1-yl), (3,5-dimethylpyrazole-1-yl), (5-methylpyrazole-1-yl), (4-methylpyrazole-1-yl), (3-methylpyrazole-1-yl), pyrazole-1-yl, cyclopropyl, or 1-cyanocyclopropyl. Preferably, R 10a R 10b Independently selected from hydrogen, chlorine, fluorine, bromine, methoxy, cyano, amino, carboxyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (5-chloropyrazol-1-yl), (4-chloropyrazol-1-yl), (3-chloropyrazol-1-yl), (5-fluoropyrazol-1-yl), (4-fluoropyrazol-1-yl), (3-fluoropyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. More preferably, R 10a R 10bIndependently selected from hydrogen, chlorine, bromine, methoxy, cyano, amino, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, (3-cyanopyrazol-1-yl), (4-cyanopyrazol-1-yl), (3,5-dimethylpyrazol-1-yl), (5-methylpyrazol-1-yl), (4-methylpyrazol-1-yl), (3-methylpyrazol-1-yl), pyrazol-1-yl, cyclopropyl, or 1-cyanocyclopropyl. Even more preferably, R 10a R 10b It is independently selected from hydrogen, chlorine, bromine, cyano or cyclopropyl.

[0071] In another embodiment of the invention, R 10 Selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl. Preferably, R 10 It is selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl.

[0072] In another embodiment of the invention, R 10 It is R 10a Or R 10b , where R 10a R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl. Preferably, R 10a R 10b It is independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl.

[0073] In one embodiment of the present invention, R 11 It is hydrogen or C1-C4-alkyl. Preferably, R 11 It is hydrogen or C1-C3-alkyl. More preferably, R 11 It is hydrogen, methyl, or ethyl. Even more preferably, R 11 It is hydrogen, or methyl. Even more preferably, R 11 It is hydrogen.

[0074] In one embodiment of the present invention, Z 1It is a C1-C4 alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl groups contains 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl groups is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthioalkyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, or C2-C4-alkynyl. Preferably, Z 1 It is a C1-C3-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl groups contains 1, 2, or 3 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl groups is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from: halogen, cyano, C1-C3-alkyl, C1-C2-haloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C1-C2-alkylthioalkyl, C1-C2-alkylsulfinyl, C1-C2-alkylsulfonyl, or C2-C4-alkynyl. More preferably, Z 1 It is a C1-C3-alkyl, phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, or C3-C6-cycloalkyl; wherein any one of the phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from: halogen, cyano, C1-C3-alkyl, C1-C2-haloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C1-C2-alkylthioalkyl, C1-C2-alkylsulfinyl, C1-C2-alkylsulfonyl, or C2-C4-ynyl. Even more preferably, Z 1 It is a C1-C3-alkyl, phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, or C3-C6-cycloalkyl, wherein any one of the phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, and C3-C6-cycloalkyl is unsubstituted or substituted by one, two, or three substituents independently selected from: halogen, C1-C3-alkyl, C1-C3-alkoxy, or C2-C4-ynyl. Even more preferably, Z 1It is a C1-C3-alkyl, phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, or C3-C6-cycloalkyl group, wherein any one of the phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, and C3-C6-cycloalkyl groups is unsubstituted or substituted by one, two, or three substituents independently selected from the group consisting of chlorine, fluorine, methyl, methoxy, or ethynyl.

[0075] In another embodiment of the invention, Z 1 Selected from 1-methylpyrazol-4-yl, 2,3,4-trifluorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 2,4,6-trifluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 3,5-difluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3-fluoro-2-pyridyl, 2-fluoro-4-methoxy-phenyl, 2-fluoro-4-methylsulfonyl-phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluoro-2-furanyl 3-Fluoro-2-furanyl, 5-Fluoro-2-furanyl, 3,5-difluoro-2-thienyl, 3-Fluoro-2-thienyl, 5-Fluoro-2-thienyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-ethynyl-2-fluoro-phenyl, 4-fluoro-2-methoxy-phenyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, methyl, n-propyl, and phenyl. Preferably, Z 1 Selected from 1-methylpyrazol-4-yl, 2,3,4-trifluorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 2,4,6-trifluorophenyl, 2,4-difluorophenyl, 3,5-difluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3-fluoro-2-pyridyl, 2,5-difluorophenyl, 2-fluoro-4-methoxy-phenyl, 2-fluoro-4-methylsulfonyl-phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluoro-2-furanyl 3-Fluoro-2-furanyl, 5-Fluoro-2-furanyl, 3,5-difluoro-2-thienyl, 3-Fluoro-2-thienyl, 5-Fluoro-2-thienyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-ethynyl-2-fluoro-phenyl, 4-fluoro-2-methoxy-phenyl, cyclopropyl, 1-methylcyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, methyl, n-propyl, or phenyl. More preferably, Z 1Selected from 1-methylpyrazol-4-yl, 2,4,6-trifluorophenyl, 2,4-difluorophenyl, 3,5-difluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3-fluoro-2-pyridyl, 2,5-difluorophenyl, 2-chlorophenyl, 2-fluorophenyl, 3,5-difluoro-2-furanyl, 3-fluoro-2-furanyl, 5-fluoro-2-furanyl, 3,5-difluoro-2-thienyl, 3-fluoro-2-thienyl, 5-fluoro-2-thienyl, 2-methylphenyl, 2-thienyl, 3,4-difluorophenyl, 3-chlorophenyl, 3-fluorophenyl, 3-methylphenyl, 3-thienyl, 4-fluoro-2-methoxy-phenyl, 4-fluorophenyl, 4-methylphenyl, cyclobutyl, cyclohexyl, cyclopentyl, methyl, or phenyl. Even more preferably, Z 1 The compound is selected from 1-methylpyrazol-4-yl, 2,4,6-trifluorophenyl, 2,4-difluorophenyl, 3,5-difluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3-fluoro-2-pyridyl, 2-fluorophenyl, 3,5-difluoro-2-furanyl, 3-fluoro-2-furanyl, 5-fluoro-2-furanyl, 3,5-difluoro-2-thienyl, 3-fluoro-2-thienyl, 5-fluoro-2-thienyl, 2-methylphenyl, 2-thienyl, 3,4-difluorophenyl, 3-chlorophenyl, 3-thienyl, 4-fluoro-2-methoxy-phenyl, 4-fluorophenyl, cyclobutyl, cyclohexyl, cyclopentyl, methyl, or phenyl. Even more preferably, Z 1 It is selected from 2,4-difluorophenyl, 3,5-difluoro-2-pyridyl, 5-fluoro-2-pyridyl, 3-fluoro-2-pyridyl, 3,5-difluoro-2-furanyl, 3-fluoro-2-furanyl, 5-fluoro-2-furanyl, 3,5-difluoro-2-thiophenyl, 3-fluoro-2-thiophenyl, 5-fluoro-2-thiophenyl, 2-fluorophenyl, 4-fluorophenyl, or phenyl.

[0076] In another embodiment of the invention, Z 1 The group is selected from phenyl, 5- to 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein the 5- or 6-membered heteroaryl comprises one heteroatom selected from N or S; and wherein the phenyl and the 5- to 6-membered heteroaryl are unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, or C1-C4 alkoxy, and wherein the C3-C6-cycloalkyl is unsubstituted or substituted by one substituent selected from halogen or C1-C4 alkyl. Preferably, Z 1 The aryl group is selected from phenyl or 5- to 6-membered heteroaryl groups; wherein the 5- or 6-membered heteroaryl group contains one heteroatom selected from N or S; and wherein the phenyl and the 5- to 6-membered heteroaryl group are unsubstituted or substituted by one or two substituents independently selected from: fluorine, chlorine, C1-C4 alkyl, or C1-C4 alkoxy. More preferably, Z 1Selected from 2,4,6-trifluorophenyl, 3,5-difluoro-2-pyridyl, 2,4-difluorophenyl, 2-fluorophenyl, 2-methylphenyl, 3,4-difluorophenyl, 3-chlorophenyl, 4-fluoro-2-methoxy-phenyl, 4-fluorophenyl, or phenyl. Even more preferably, Z 1 It is selected from 2,4-difluorophenyl, 3,5-difluoro-2-pyridyl, 2-fluorophenyl, 4-fluorophenyl, or phenyl.

[0077] Therefore, the present invention makes it possible to obtain compounds having formula (I) having R as defined above with respect to formula (I) in all combinations / permutations. 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 A 1 A 2 A 3 B 1 B 2 B 3 and Z 1 .

[0078] In embodiments of the present invention, a compound having formula (I) may be a compound having formula (II):

[0079] (II)

[0080] in

[0081] R 1 R 2 R 3 R 4 R 5 R 6 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-3, A-4, A-5, A-6, A-7, or A-8:

[0082]

[0083] in (Dashed line) indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the group bond, and where R 7 R 8 and R 9 It is independently selected from hydrogen, halogen, C1-C3 alkyl, C3-C6 cycloalkyl, or C1-C3 haloalkyl.

[0084] In one embodiment of the present invention, R 7 R 8 and R 9 It is independently selected from hydrogen, halogen, or trifluoromethyl.

[0085] In another embodiment of the invention, a compound having formula (II), wherein R 1 R 2 R 3 R 4 R 5 R 6 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 As defined for compounds of formula (I) according to the invention, A is selected from A-1, A-2, A-3, A-4, A-5, A-6, A-7, or A-8; wherein the dashed line indicates the bond to the C (=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group: and where R 7 R 8 and R 9 It is hydrogen.

[0086] In another embodiment of the invention, a compound having formula (II), wherein R 1 R 2 R 3 R 4 R 5 R 6 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 It is as defined for compounds having formula (I) according to the invention.

[0087] A is selected from A-1, A-2, A-4, or A-5,

[0088]

[0089] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; and where R 7 and R 8 It is hydrogen.

[0090] In another embodiment of the invention, in a compound having formula (II), wherein R 1 R 2 R 3 R 4 R 5 R 6 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 As defined for compounds of formula (I) according to the invention, A is selected from A-1 or A-2.

[0091]

[0092] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom in the group bond.

[0093] In one embodiment of the invention, a compound having formula (II), wherein R 1 R 2 R 3 R 4 R 5 R 6 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 As defined for compounds of formula (I) according to the invention, A is A-1.

[0094] A-1

[0095] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom in the group bond.

[0096] In another embodiment of the invention, a compound having formula (II), wherein R 1 R 2 R 3 R 4 R 5 R 6 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 As defined for compounds of formula (I) according to the invention, A is A-2.

[0097] A-2

[0098] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom in the group bond.

[0099] In one embodiment of the present invention, a compound having formula (I) may be a compound having formula (III):

[0100] (III)

[0101] Where R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-3, A-4, A-5, A-6, A-7, or A-8; and Q is selected from Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, or Q-20.

[0102]

[0103] The dashed lines indicate bonds extending to the rest of the molecule, and R... 10a R 10bIndependently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkoxy-C1-C4-alkyl, N-C1-C4-alkylamino, N,N-di-(C 1- C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms individually selected from N, O or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and R 11 Selected from hydrogen or C1-C4 alkyl groups.

[0104] In another embodiment of the invention, the compound having formula (I) can be a compound having formula (III), wherein R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-3, A-4, A-5, A-6, A-7, or A-8; Q is selected from Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, or Q-20; R 10a R 10b Independently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1 or 2 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and R 11 It is either hydrogen or methyl.

[0105] In another embodiment of the invention, the compound having formula (I) can be a compound having formula (II), wherein R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-3, A-4, A-5, A-6, A-7, or A-8; Q is selected from Q-1, Q-2, Q-3, Q-4, Q-5, Q-6, Q-7, Q-8, Q-9, Q-10, Q-11, Q-12, Q-13, Q-14, Q-15, Q-16, Q-17, Q-18, Q-19, or Q-20; R 10a R 10b Independently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1 or 2 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and R 11 It is hydrogen.

[0106] In another embodiment of the invention, the compound having formula (I) can be a compound having formula (II), wherein

[0107] R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-4, or A-5;

[0108]

[0109] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, Q-3, Q-7, Q-8, Q-9, Q-10, Q-12 or Q-15;

[0110]

[0111] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10b Independently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1 or 2 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and R 11 It is either hydrogen or methyl.

[0112] In another embodiment of the invention, the compound having formula (I) can be a compound having formula (II), wherein

[0113] R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-4, or A-5;

[0114]

[0115] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, Q-3, Q-7, Q-8, or Q-9;

[0116]

[0117] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10b Independently selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1-C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, or 3 heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by 1 or 2 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; and R 11 It is either hydrogen or methyl.

[0118] In another embodiment of the invention, the compound having formula (I) can be a compound having formula (II), wherein

[0119] R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-4, or A-5;

[0120]

[0121] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, Q-3, Q-7, Q-8, or Q-9;

[0122]

[0123] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10bIndependently selected from hydrogen, halogen, cyano, amino, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any of the 5- or 6-membered heteroaryl contains one heteroatom selected from N; and wherein any of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, methyl, ethyl, or trifluoromethyl; and R 11 It is either hydrogen or methyl.

[0124] In another embodiment of the invention, the compound having formula (I) can be a compound having formula (II), wherein

[0125] R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 As defined for compounds having formula (I) according to the invention, A is selected from A-1, A-2, A-4, or A-5;

[0126]

[0127] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, or Q-3;

[0128]

[0129] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10b The group is independently selected from hydrogen, halogen, cyano, amino, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C3-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains one heteroatom selected from N; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, methyl, ethyl, or trifluoromethyl.

[0130] Therefore, the present invention makes it possible to obtain compounds having formula (I) having R as defined above with respect to formula (I) in all combinations / permutations. 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 A 1 A 2 A 3 B 1 B 2 B 3 and Z 1 .

[0131] Therefore, the present invention makes it possible to obtain compounds having formula (II) having R as defined above with respect to formula (I) in all combinations / permutations. 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 , and A regarding equation (II).

[0132] Therefore, the present invention makes it possible to obtain compounds having formula (II) having R as defined above with respect to formula (I) in all combinations / permutations. 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 and Z 1 , A with respect to equation (II), and Q with respect to equation (III).

[0133] Embodiments of the present invention are provided, as listed below.

[0134] In one embodiment, a compound having formula (I) is provided, wherein R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; R 5 and R 6 Independently selected from hydrogen or C1-C3 alkyl; and A 1 A 2 A 3 R 7 R 8 R 9 R 10 R 11 B 1 B 2 B 3 and Z 1 It is as defined for compounds having formula (I).

[0135] In one embodiment, a compound having formula (I) is provided, wherein R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; R 5 and R 6 Independently selected from hydrogen or C1-C3 alkyl; A 1 Is it CH or N, A 2 It is CH or N; and A 3 Is it CH or N, B? 1 B 2 B 3 Independently selected from CR 10 N, O, or S, provided that B is a given. 1 B 2 B 3 No more than one of them is O or S; R 10 It is R 10a Or R 10b , where R 10a R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1It is as defined for compounds having formula (I).

[0136] In one embodiment, a compound having formula (I) is provided, wherein R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; R 5 and R 6 Independently selected from hydrogen or C1-C3 alkyl; A 1 Is it CH or N, A 2 It is CH or N; and A 3 Is it CH or N, B? 1 B 2 B 3 Independently selected from CR 10 N, O, or S, provided that B is a given. 1 B 2 B 3 No more than one of them is O or S; R 10 It is R 10a Or R 10b , where R 10a R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1 It is a C1-C3-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any of the 5- or 6-membered heteroaryl contains one or two heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, C1-C3-alkyl, C1-C2-haloalkyl, or C1-C3-alkoxy.

[0137] In one embodiment, a compound having formula (I) is provided, wherein R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; R 5 and R6 Independently selected from hydrogen or C1-C3 alkyl; A 1 Is it CH or N, A 2 It is CH or N; and A 3 It is CH or N; B 1 B 2 B 3 Independently selected from CR 10 N, O, or S, provided that B is a given. 1 B 2 B 3 No more than one of them is O or S; R 10 Selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1 It is a C1-C3-alkyl, phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, or C3-C6-cycloalkyl group, wherein any one of the phenyl, pyrazolyl, thiophenyl, pyridyl, furanyl, and C3-C6-cycloalkyl groups is unsubstituted or substituted by one, two, or three substituents independently selected from the group consisting of chlorine, fluorine, methyl, methoxy, or ethynyl.

[0138] In one embodiment, a compound having formula (I) is provided, wherein R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; R 5 and R 6 Independently selected from hydrogen or C1-C3 alkyl; A 1 Is it CH or N, A 2 It is CH or N; and A 3 It is CH or N; B 1 B 2 B 3 Independently selected from CR 10 N, O, or S, provided that B is a given. 1 B 2 B 3 No more than one of them is O or S; R 10 Selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1 It is phenyl or pyridyl, wherein either the phenyl or pyridyl group is unsubstituted or substituted by one or two substituents independently selected from the group consisting of chlorine, fluorine, methyl, or methoxy.

[0139] In one embodiment of the invention, the compound having formula (I) can be a compound having formula (III-A), wherein R 4 and R 5 It is hydrogen, and

[0140] (III-A)

[0141] Where R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; A is selected from A-1, A-2, A-4, or A-5.

[0142]

[0143] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, or Q-3;

[0144]

[0145] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1 It is as defined for compounds having formula (I).

[0146] In one embodiment of the invention, the compound having formula (I) can be a compound having formula (III-A), wherein R 4 and R 5 It is hydrogen, and

[0147] (III-A)

[0148] Where R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4Selected from hydrogen, cyano, or C1-C3-alkyl; A is selected from A-1, A-2, A-4, or A-5.

[0149]

[0150] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1 The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, or Q-3;

[0151]

[0152] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1 It is a C1-C3-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any of the 5- or 6-membered heteroaryl contains one or two heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, C1-C3-alkyl, C1-C2-haloalkyl, or C1-C3-alkoxy.

[0153] In one embodiment of the invention, the compound having formula (I) can be a compound having formula (III-A), wherein R 4 and R 5 It is hydrogen, and

[0154] (III-A)

[0155] Where R 1 Selected from hydrogen, C1-C3-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C3-alkyl, or cyclopropyl; R 3 Selected from hydrogen, halogen, or C1-C4 alkyl; R 4 Selected from hydrogen, cyano, or C1-C3-alkyl; A is selected from...

[0156]

[0157] The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to Z 1The nitrogen atom of the bond in the group; Q is selected from Q-1, Q-2, or Q-3;

[0158]

[0159] The dashed lines indicate bonds extending to the rest of the molecule; R 10a R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and Z 1 It is phenyl or pyridyl, wherein either the phenyl or pyridyl group is unsubstituted or substituted by one or two substituents independently selected from the group consisting of chlorine, fluorine, methyl, or methoxy.

[0160] The presence of one or more possible asymmetric carbon atoms in any of the compounds according to the invention selected from those having formula (I), (II), (III), or (III-A), or those selected from those listed in Tables C-1 to C-60 or Table P (hereinafter) means that these compounds can exist in chiral isomers (i.e., enantiomers or diastereomers).

[0161] More preferably, the compound having formula (I) according to the invention is selected from the compounds listed in any one of Tables C-1 to C-60.

[0162] Even more preferably, the compounds having formula (I) according to the invention are selected from the compounds listed in Table P (hereinafter).

[0163] The compounds defined in any embodiment of the invention may be prepared as shown in schemes 1 to 8 below, wherein (unless otherwise stated) each variable is defined as above in any embodiment of the invention.

[0164] More specifically, a compound having formula (I) can be produced by a compound having formula (III) or a salt thereof (where R... 1 R 2 R 3 R 4 R 5 R 6 Q and Q are as defined above for compounds having formulas (I) and (III) by means of a compound having formula (II) (where A) 1 A 2 A 3 and Z 1 It is prepared by the reaction as defined above for compounds having formula (I). This reaction is shown in Scheme 1.

[0165]

[0166] Option 1

[0167] In scheme 1, by means of methods known to those skilled in the art and described in, for example Tetrahedron 2005, 61 The method in (46), 10827-10852, is used to process compounds having formula (II) (where A) 1 A 2 A 3 and Z 1 (As defined above for compounds having formula (I)) activated to form compounds having formula (IIa). For example, compounds having formula (IIa) (where X) 0 (It is a halogen) is formed by treating a compound having formula (II) with, for example, oxalyl chloride or thionyl chloride in the presence of a catalytic amount of N,N-dimethylformamide (DMF) in an inert solvent (such as dichloromethane (DCM) or tetrahydrofuran (THF)) at a temperature between 20°C and 100°C, preferably 25°C. It is formed by treating a compound having formula (III) (wherein R...) with... 1 R 2 R 3 R 4 R 5 R 6 (And Q are as defined above for compounds having formulas (I) and (III)) The compound having formula (IIa) is optionally treated in the presence of a base (e.g., triethylamine (TEA) or pyridine) to give the compound having formula (I). Alternatively, the compound having formula (I) can be obtained by treating the compound having formula (II) in an inert solvent (e.g., pyridine, DMF, acetonitrile, DCM, or THF), optionally in the presence of a base (e.g., TEA), at a temperature between 30°C and 180°C, with dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), or 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) to give the activated compound having formula (IIa) (where X is X). 0 It is prepared as described below (X-1, X-2, or X-3). Finally, compounds having formula (II) can also be activated by reacting with a coupling agent (such as propanephosphonic anhydride (T3P)) to provide compounds having formula (IIa) (where X... 0 It is as described below (X-4), such as in, for example, in Synthesis become] 2013 , 45,As described in 1569. Further reaction with an amine (or a salt thereof) of a compound having formula (III) yields a compound having formula (I).

[0168]

[0169] Compounds having formula (II) can be produced by compounds having formula (IIb) (where A) 1 A 2 A 3 It is N and Z 1 It is as described in equation (I), and X 0 (These are C1-C4 alkyl groups) are prepared by ester hydrolysis. Various conditions can be used, such as aqueous solutions of sodium hydroxide or lithium hydroxide, and organic-water miscible solvents like THF, dimethoxyethane, methanol, or ethanol. Such ester hydrolysis is well known to those skilled in the art. Compounds having formula (IIb) can also be directly converted to compounds having formula (I) by reacting a compound having formula (III) with a compound having formula (III) in an inert solvent (such as toluene or DCM) in the presence of trimethylaluminum or a trimethylaluminum-DABCO complex. Such reactions have been reported in the literature (see [link to literature]). Tetrahedron Lett. [Tetrahedron Letters] 1977, 4171-4174, and Tetrahedron Lett. [Tetrahedral Express] 2006, 5767-5769 and the references cited therein).

[0170] Compounds having formulas (II) and (IIb) are commercially available or can be synthesized as described below.

[0171] Compounds having formula (III) or salts thereof (where R) 1 R 2 R 3 R 4 R 5 R 6 And Q is as defined above for compounds having formulas (I) and (III) and can be obtained by a person skilled in the art from nitriles having formula (IV) (where R is a nitrile). 1 R 2 R 3 R 4 Q is prepared by reacting a suitable nucleophile (such as (dimethyl sulfide) dihydroboron (BMS)) with a suitable aprotic solvent (such as THF) as defined above for compounds having formula (I), for example, as... J. Org. Chem. [Organic Chemistry Journal] 1981 47,As described in 3153. Alternatively, Grignard reagent R 5 MgBr or R 6 MgBr (where R) 5 and R 6 As defined above for compounds having formula (I), these can be added sequentially or simultaneously as nucleophiles to compounds having formula (IV) to allow the preparation of more highly substituted amines having formula (III). In inert solvents (such as diethyl ether, tert-butyl methyl ether (TBME), and cyclopentyl methyl ether), in Lewis acids (such as Ti(O-) i In the presence of Pr)4), this type of Grignard addition to nitrile occurs (see... Synlett [Synthesis Bulletin] 2007, (4), 652-654 (Scheme 2).

[0172]

[0173] Option 2

[0174] Compounds having formula (IV) (where R) 1 R 2 R 3 R 4 Q (as defined above for compounds having formulas (I) and (III)) can be prepared by those skilled in the art using known methods. More specifically, compounds having formula (IV) and their intermediates can be prepared from compounds having formula (V), as shown in Scheme 3.

[0175]

[0176] Option 3

[0177] For example, compounds having formula (IV) (where R) 1 R 2 R 3 R 4 Q is as defined above for compounds having formula (I), and R 4 (Not hydrogen) can be produced by those skilled in the art at low temperature using a strong base (such as n-butyllithium or sodium hydride) in an inert solvent (such as THF), followed by the addition of a suitable alkylating agent R. 4 -X 0 (where X) 0 (e.g., iodomethane) will cause compounds having formula (IVa) (where R) 4 It is hydrogen and R 1 R 2 R 3And Q is prepared by deprotonation as defined above for compounds having formula (I). Compounds having formula (IVa) (where R) 4 It is hydrogen and R 1 R 2 R 3 Q (as defined above for compounds having formula (I)) can be prepared from an alcohol having formula (V) by treatment with cyanotrimethylsilane (TMSCN) in the presence of a base (such as lithium carbonate) in a nonpolar solvent (such as dichloromethane) at a temperature between 0°C and the boiling point of the reaction mixture. Such transformations are well known in the literature under various conditions, such as... Org. Lett. [ Organic Express 2008, 10 , 4570 and the references therein described.

[0178] The compound having formula (V) can be prepared from the compound having formula (VI), respectively from any one of the compounds having formulas (VIa), (VIb), (VIc), (VId), (VIe), (VIf), (VIg), (VIh), (VIi), (VIj), (VIk), (VIm), (VIn), (VIo), (VIp), (VIq), (VIr), (VIs), (VIt), and (VIu), as shown in Scheme 4.

[0179]

[0180] Option 4

[0181] As shown in Scheme 4, a compound having formula (VII) (where R) will be used. 1 R 2 and R 3 It is as defined above for compounds having formula (I) and X 01 (Whether it is bromine or iodine) is metallized with a suitable reagent such as a turbo Grignard reagent (isopropyl magnesium chloride-lithium chloride complex) or an alkyllithium (such as n-butyllithium) to obtain an intermediate Grignard reagent or alkyllithium reagent (M is MgX). 01 Or lithium). Such metals are inserted into CX. 01The bonding is well known to those skilled in the art and is typically carried out at temperatures between -78°C and room temperature in an inert solvent (such as an ether, for example, TBME or THF). The solution of the metallized substance (VIIa) is then treated with compounds having formula (VI), specifically (VIa), (VIb), (VIc), (VId), (VIe), (VIf), (VIg), (VIh), (VIi), (VIj), (VIk), (VIm), (VIn), (VIo), (VIp), (VIq), (VIr), (VIs), (VIt), and (VIu) (as shown in Scheme 5) to obtain compounds having formula (V). Similar reactions of these types have been described, for example, in WO 2012 / 102297 and Bio. Med. Chem. Lett. [ Bioorganic and Medicinal Chemistry Letters ] 2017, 27(17), 4044-4050 (X 01 (Br, n-butyllithium) and Ang. Chem. Int. Ed. [ Angewandte Chemie International Edition ]2016, 55 (17), 5332-5336, US 2014 / 0349990, WO 2002 / 004424, WO 2021 / 009068 (X 01 It is in I, Turbo Grignard reagent).

[0182] Compounds having formulas (VI) and (VII) are commercially available or readily prepared by methods known to those skilled in the art.

[0183] Further synthesis of compounds having formula (I) involves treating a compound having formula (VIII) with a base (such as sodium hydride or n-butyllithium) in an inert solvent (such as THF), and subsequently with a compound having formula (IX) (where R... 4 It is as described in equation (I), and X 02 Alkylation of leaving groups (such as halogens, methanesulfonates, or toluenesulfonates) to produce compounds having formula (X) (Scheme 5).

[0184]

[0185] Option 5

[0186] Then, in an inert solvent (such as THF or TBME), at a temperature between -78°C and room temperature, the compound having formula (X) (where R) is treated with a strong base (such as sodium hydride or an alkyl lithium base (such as n-butyllithium)). 1 R 2 R 3 and R 4(As defined above for compounds having formula (I),) followed by the addition of compounds having formula (XI), specifically any one of the compounds having formulas (XIa), (XIb), (XIc), (XId), (XIe), (XIf), (XIg), (XIh), (XIi), (XIj), (XIk), (XIm), (XIn), (XIo), (XIp), (XIq), (XIr), (XIs), (XIt), and (XIu) (where R 10 and R 11 It is as defined above for compounds having formula (I), and X 03 (The leaving group, such as halogen, preferably fluorine, chlorine or bromine), yields a compound having formula (IV). This reaction is shown in Scheme 6.

[0187]

[0188]

[0189] Option 6

[0190] As previously described in schemes 1, 2, and 3, a compound having formula (IV) is converted into a compound having formula (I). Those skilled in the art will recognize that the conversion of compound (VIII) into a compound having formula (IV) can be carried out sequentially or in the same reaction vessel, allowing for a simplified conversion of the compound having formula (VIII) into the compound having formula (IV). This is described in more detail in the preparation examples.

[0191] Compounds having formula II are commercially available or can be obtained as follows: See below The described synthesis.

[0192] Compounds having formula (IIb), wherein A 1 A 2 A 3 It is N and Z 1 It is as described in formula (I), that is, a compound having formula (IIba).

[0193] (IIba)

[0194] The diazonium salt having formula (XII) can be obtained by the following reaction.

[0195] (XII)

[0196] Z 1 It is as defined above under Equation I and Y- It is a counter ion, depending on the conditions under which the diazotization step takes place, for example, Cl... - Or BF4 - and compounds having formula (XIV),

[0197] (XIV)

[0198] Where R 0 It is a C1-C6 alkyl group. This reaction can be catalyzed by various silver salts, with silver acetate being the preferred silver salt, and carried out in various solvents (e.g., THF, DMF, or toluene or mixtures thereof), typically at temperatures between 0°C and 25°C, in the presence of at least one equivalent of a base (e.g., sodium carbonate). These dipolar [3+2] cycloadditions are highly regioselective and are described in, for example... Tetrahedron [tetrahedron] 2020, 76(14), 131063. As previously defined, compounds having formula (XII) can be prepared from primary amines having formula (XIII) by reacting with a diazotizing agent (e.g., a salt of nitrite, such as sodium nitrite). The solvent can be an aqueous solution of an acid, such as dilute hydrochloric acid or tetrafluoroboric acid. Counterion Y - The diazotization reaction is defined by the acid used. Diazotization is commonly used in organic synthesis, even on an industrial scale, and is known to those skilled in the art.

[0199] To reduce the risk of decomposition of the intermediate with formula (XII), the diazotization and cycloaddition steps can be performed sequentially without the need to separate (XII). This variant also... Tetrahedron As described in 2020, 76(14), 131063 (Scheme 7).

[0200]

[0201] Option 7

[0202] Compounds having formula (XIII) are commercially available, as are compounds having formula (XIV) (e.g., R...). 0 It is methyl, as is CAS [6832-16-2]).

[0203] Very similarly, compounds having the formula (IIba) (where A) 1 A 2 A 3 It is N and Z 1 (As described in formula (I)) can be achieved by making compounds having formula (XV):

[0204] (XV)

[0205] Where R 0 It is a C1-C6 alkyl group and Ar 1 It is prepared by reacting a phenyl or p-tolyl compound with a compound having formula (XII) in the presence of a base (e.g., pyridine) at a temperature from -50°C to 50°C to produce a compound having formula (IIba). Such reactions have been well precedented in, for example, the following literature: Chem. Comm. [ Chemical Communications ]2017, 53(69), 9620-9623, Ang. Chem. Int. Ed . [ Angewandte Chemie International Edition ] 2017, 56(47), 15044-15048, and J. Am. Chem. Soc . [ Journal of the American Chemical Society [2016, 138(44), 14609-14615. Compounds having formula (XV) are prepared as described in the references cited above and illustrated in the preparation examples of this application.]

[0206] Alternatively, compounds having the formula (IIba) (where A) 1 A 2 and A 3 It is N and Z 1 (As defined in formula (I)) can be obtained by coupling a compound having formula (XVI),

[0207] (XVI)

[0208] Where A 1 A 2 and A 3 It is N, and R 0 yes As mentioned above The described boric acid derivatives having formula (XVII)

[0209] (XVII)

[0210] Z 1 It is as defined in Formula I. This Chan-Lam type coupling reaction is typically carried out in a solvent (like dichloromethane), in the presence of a catalytic amount of a copper-based catalyst, at a mild reaction temperature, in the presence of a base (like potassium carbonate), under atmospheric or oxygen conditions. It should be noted that compounds having formula (XVI) (where A...) 1 A 2 and A 3 N) exists in the form of tautomerism. Right now;

[0211]

[0212] Those skilled in the art will envision that the coupling products of this reaction could be one of the regioisomers or a mixture thereof, but when the reaction conditions are as follows... J. Org. Chem. [Journal of Organic Chemistry] 2014 When selected as described in 79, 6703-6707, this reaction exhibits excellent regioselectivity for compounds having formula (IIba). Those skilled in the art will recognize that this Chan-Lam coupling is a general method for preparing compounds having formula (IIb). Examples of compounds having formula (IIbb) are shown in the literature.

[0213] (IIbb)

[0214] Z 1 R 12a and R 0 It is as previously defined (see J. Med. Chem. [Journal of Medicinal Chemistry] 2018, 61, 8, 3370-3388 and WO 14 / 041106), compounds having formulas (IIbc) and (IIbd).

[0215] (IIbc), (IIbd)

[0216] Z 1 R 12a R 13a R 14a and R 0 It is a compound as defined under formula (I) (see WO 15 / 155626, EP2390252) and having formula (IIbe).

[0217] (IIbe)

[0218] Z 1 R 12a R 13a R 14a and R 0 It is as defined under equation (I) (see J. Med. Chem . [ Drugification Journal of Studies ] 2017, 60(14), 6166-6190, Org. Lett . [ Organic Express ] 2008, 10(8), 1653-1655, and Bio. Med. Chem. Lett. [Bioorganic and Medicinal Chemistry Letters] (2009, 19(5), 1451-1456), as a representative example.

[0219] Used to prepare compounds having the formula (IIba) (where A) 1 A 2 and A 3 It is N and Z 1 Another method (as defined in equation (I)) is shown in scheme 8.

[0220]

[0221] Option 8

[0222] As shown in Scheme 12, the sequence begins as follows: See above The previously described diazotization of the compound having formula (XII) and then, in the presence of a mild base (e.g., sodium acetate), the use of a compound having formula (XVIII) (where R... 0 The diazonium salt is treated with C1-C6 alkyl groups to produce a compound having the formula (XIX). Then, the compound having the formula (XIX) (where Z is C1-C6 alkyl) is treated with ammonia in a miscible organic solvent (e.g., THF or 2-methyl-THF) at a temperature between 0°C and 30°C. 1 and R 0 (As previously defined), to obtain a compound having formula (XX). Finally, the compound having formula (XX) is diazotized with a salt of nitrite (e.g., sodium nitrite) in a slightly acidic medium (e.g., aqueous solution of acetic acid or hydrochloric acid) at a temperature between -20°C and 0°C, resulting in the spontaneous cyclization of the formed diazonium salt to a tetrazolium compound having formula (IIba). The reaction sequence has previously been described in WO 13 / 087805, 2013 As described in the text.

[0223] Compounds having formula (IIb) can also be produced by using compounds having formula (XVI).

[0224] (XVI)

[0225] Using compounds with the formula (XXI)

[0226] (XXI)

[0227] Z 1 It is as previously described under equation (I) and X 0This is prepared by alkylation of a halogen (preferably chlorine, bromine, or iodine) in an inert aprotic or proton solvent in the presence of a base (e.g., alkaline earth metal bases such as NaOH, KOH, LiOH, Cs₂CO₃, K₂CO₃, etc.). Such alkylation is well known to those skilled in the art and has been used in this context to prepare compounds having formula (IIb), as described, for example, in WO 14 / 168221, WO 10 / 043000, and WO 14 / 32498. Those skilled in the art will recognize that this can yield mixtures of regioisomers that can be separated by chromatographic techniques, or pure isomers can be obtained by prudent selection of conditions and additives (e.g., palladium catalysts for so-called Buchwald amination). For Z... 1 In the case of heteroaryl or aryl compounds, the SnAr reaction (with or without copper catalysis) can be used to prepare compounds having formula (IIb) (see, for example, Polyhedron [polyhedron] 2019, 165,22-30; US 18 / 0170909; Org. Lett. [Organic Bulletin] 2022, 24(20), 3620-3625; J. Org. Chem. [Journal of Organic Chemistry] 2017, 82(14), 7420-7427; Chem. Comm. [Chemical Communications] 2021, 57(57), 7047-7050; ACS Catalysis [ACS catalysis] 2019, 9(12), 10674-10679; Synthesis [synthesis] 2017, 49(23), 5120-5130; J. Org. Chem. [Journal of Organic Chemistry] 2019, 84(12), 8160-8167; and the references cited therein).

[0228] A compound having formula (I) as defined in any embodiment of the invention can be converted into another compound as defined in any embodiment of the invention in a manner known per se by replacing one or more substituents of the starting compound in a conventional manner with another substituent according to the invention. Those skilled in the art will also understand that a compound having formula (I) can be further converted into other derivatives having formula (I) by, for example, alkylation, nucleophilic substitution, elimination, C / C bond formation reactions in the presence of a metal catalyst, heteroatom-carbon bond formation in the presence of a metal catalyst, oxidation, and reduction.

[0229] Depending on the chosen reaction conditions and starting materials appropriate to the specific circumstances, it may be possible, for example, to replace only one substituent with another substituent according to the invention in a single reaction step, or to replace multiple substituents with other substituents according to the invention in the same reaction step.

[0230] Salts of compounds having formula (I) can be prepared in ways known per se. Thus, for example, acid addition salts of compounds having formula (I) are obtained by treatment with a suitable acid or a suitable ion exchange reagent, and salts with a base are obtained by treatment with a suitable base or a suitable ion exchange reagent.

[0231] Salts of compounds having formula (I) can be converted in a conventional manner into free compound (I), acid addition salts (e.g., by treatment with a suitable basic compound or a suitable ion exchange reagent), and salts with bases (e.g., by treatment with a suitable acid or a suitable ion exchange reagent).

[0232] Salts of compounds having formula (I) can be converted in a manner known per se into other salts of compounds having formula (I), acid addition salts, for example, into other acid addition salts, such as by treating salts of inorganic acids (e.g., hydrochlorides) in a suitable solvent with a suitable metal salt of the acid (e.g., a salt of sodium, barium, or silver, e.g., silver acetate), in which the inorganic salt (e.g., silver chloride) formed is insoluble and thus precipitates out of the reaction mixture.

[0233] Depending on the procedure or reaction conditions, compounds of formula (I) with salt-forming properties can be obtained either in free form or as salts.

[0234] Compounds having formula (I) and, where appropriate, their tautomers (in each case, in free form or in salt form) can exist in one of the possible isomers or in mixtures of these isomers, for example, in the form of pure isomers (such as enantiomers and / or diastereomers) or in the form of mixtures of isomers (such as mixtures of enantiomers, e.g., racemic mixtures; mixtures of diastereomers or mixtures of racemic mixtures), depending on the number of asymmetric carbon atoms present in the molecule, the absolute and relative configurations and / or depending on the configuration of the non-aromatic double bonds present in the molecule; the present invention relates to pure isomers and all possible mixtures of isomers, and should be understood in this sense in every context, even in every case where stereochemical details are not specifically mentioned.

[0235] The compounds of formula (I) of the present invention exhibit asymmetric carbon atoms at the bisbenzyl position:

[0236] Those skilled in the art will readily recognize that both enantiomers are within the scope of this invention.

[0237] A mixture of diastereomers or racemates of compounds of formula (I) in free or salt form (their acquisition may depend on the selected starting materials and procedures) can be isolated into pure diastereomers or racemates in a known manner, based on the physicochemical differences of these components, for example by fractional crystallization, distillation and / or chromatography.

[0238] Enantiomer mixtures (such as racemates) that can be obtained in a similar manner can be resolved into optical enantiomers by known methods, such as by recrystallization from an optically active solvent; by chromatography on a chiral adsorbent, such as high-performance liquid chromatography (HPLC) on acetylcellulose; by cleavage with a specific immobilized enzyme using suitable microorganisms; by forming a containing compound, such as using a chiral crown ether, in which only one enantiomer is complexed; or by conversion into salts of diastereomers, such as by reacting the basic final product racemate with an optically active acid (such as a carboxylic acid, such as camphoric acid, tartaric acid, or malic acid, or a sulfonic acid, such as camphorsulfonic acid), and the diastereomer mixtures that can be obtained in this manner can be separated, for example by fractional crystallization based on their different solubilities, to obtain diastereomers from which the desired enantiomers can be freed by the action of suitable reagents (such as basic reagents).

[0239] Pure diastereomers or enantiomers can be obtained according to the invention, not only by separating a suitable mixture of isomers, but also by methods of commonly known diastereoselective or enantiomeric synthesis, for example by using starting materials with suitable stereochemistry according to the invention.

[0240] If individual components have different biological activities, it is advantageous to isolate or synthesize biologically more effective isomers in each case, such as enantiomers or diastereomers or mixtures of isomers, such as mixtures of enantiomers or mixtures of diastereomers.

[0241] As an example, compounds having more than one asymmetric carbon atom can exist in diastereomer form, which can optionally be separated using, for example, supercritical fluid chromatography (SFC) with a chiral column. Such diastereomers can exhibit different antifungal activity characteristics, but all isomers and diastereomers form part of this invention.

[0242] The compounds of formula (I) of the present invention exhibit two asymmetric carbon atoms. The relationship between the enantiomers and diastereomers of the compounds of formula (I) is shown below.

[0243]

[0244] Those skilled in the art will readily recognize the diastereomers and enantiomers (where R) of the above having formula (I). 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R 10 R 11 A 1 A 2 A 3 B 1 B 2 B 3 and Z 1 (as defined above for formula (I)) is within the scope of this invention.

[0245] Furthermore, those skilled in the art will readily recognize that the above-described diastereomers and enantiomers are applicable to compounds having formulas (I), (III), and (III-A) (wherein R...). 1 R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 A 1 A 2 A 3 A, Q and Z 1 (as defined for formulas (I), (II), or (III)) and within the scope of this invention.

[0246] Compounds having formula (I) and, where appropriate, their tautomers (in each case, in free or salt form) can also be obtained as hydrates and / or include other solvents, such as those that can be used to crystallize compounds that exist in solid form.

[0247] As indicated, surprisingly, it has now been found that, for practical purposes, the compounds of formula (I) of the present invention have a very favorable level of bioactivity for protecting plants against diseases caused by fungi.

[0248] Compounds of formula (I) according to the present invention can be used in the agricultural sector and related application fields as active ingredients, for example, for controlling plant pests, or for controlling putrefactive microorganisms or potentially harmful organisms on non-living materials. These novel compounds are characterized by excellent activity at low application rates, good plant tolerance, and environmental safety. They have very useful therapeutic, preventative, and systemic properties and can be used to protect many cultivated plants. Compounds of formula (I) can be used to inhibit or destroy pests appearing on plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) of various useful plant crops, while also protecting those plant parts that grow later from, for example, plant pathogenic microorganisms.

[0249] The present invention further relates to a method for controlling or preventing infection of microbially susceptible plants or plant propagation materials and / or harvested food crops by treating plants or plant propagation materials and / or harvested food crops, wherein an effective amount of a compound having formula (I) according to the invention is applied to the plant, its parts or the site thereof.

[0250] As used herein, when applied in the context of infection of plants or plant propagation material and / or harvested food crops, the term “control” means reducing the number of pests, eliminating pests and / or preventing further pest damage, thereby reducing damage to plants or plant-derived products.

[0251] When used in the context of infection of plants or plant propagation material and / or harvested food crops, the term "prevention" refers to the avoidance of symptoms caused by microbial invasion or fungal infection (fungal growth).

[0252] Compounds having formula (I) according to the invention can also be used as fungicides. As used herein, the term "fungicide" means a compound that controls, alters, or prevents fungal growth. The term "fungicide effective amount" in use means, when used, the amount of such compound or combination of such compounds that can affect fungal growth. Controlling or altering effects include all deviations from natural development, such as killing, inhibiting, etc., and prevention includes the formation of barriers or other defenses within or on the plant to prevent fungal infection.

[0253] It is also possible to use compounds of formula (I) according to the invention as seed dressings for treating plant propagation material (e.g., seeds, fruits, tubers, or grains) or plant cuttings to protect against fungal infections and against plant pathogenic fungi present in the soil. Propagation material can be treated with a composition containing a compound of formula (I) before planting: for example, seed dressing can be applied before sowing. The active compound of formula (I) can also be applied to grains (coating) by impregnating seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when planting the propagation material, for example, by applying it to the furrows of the seeds during sowing. The invention also relates to such methods of treating plant propagation material, and to plant propagation material treated in this way.

[0254] Furthermore, the compounds of formula (I) according to the present invention can be used to control fungi in relevant fields, such as in the protection of industrial materials (including wood and wood-related technical products), in food storage, and in hygiene management.

[0255] In addition, the present invention can also be used to protect non-living materials (such as wood, wall panels and coatings) from fungal invasion.

[0256] The compounds of formula (I) according to the present invention are effective against pathogenic fungi and fungal vectors, as well as plant pathogenic bacteria and viruses. These pathogenic fungi and their vectors, as well as plant pathogenic bacteria and viruses, include, for example: *Pyrrosia lingua*, *Alternaria* species, *Hymenopterus* species, *Cyclophorus* species, *Aspergillus* species (including *Aspergillus flavus*, *Aspergillus fumigatus*, *Aspergillus nidus*, *Aspergillus niger*, *Aspergillus terreus*), *Blastomyces* species (including *A. pullulans*), *Blastomyces dermatitidis*, *Powdery mildew fungus*, *Bremia lactucae*, *Botrytis* species (including *B. dothidea*, *B. obtusa*), *Botrytis* species (including *B. cinerea*), *Candida* species (including *Candida albicans*, *Candida glabrata*, *Candida krusei*, *Candida lusitaniae*, *Candida parapsilosis*, *Candida tropicalis*). Tropicis), Cephaloascus fragrans, species of the genus *Cercosporidium*, species of the genus *Cercosporidium* (including *Cercosporidium arachidicola*), *Cercosporidium personatum*, species of the genus *Cladosporium*, *Cercosporidium*, *Cercosporidium*, species of the genus *Cercosporidium*, species of the genus *Anthracis* (including *Cercosporidium musae*), *Cryptococcus neoformans*, species of the genus *Diaporthe ... *Langsethiae*, *Fusarium moniliforme*, *Fusarium glomeratum*, *Fusarium solanum*, *Fusarium oxysporum*, *Fusarium latrinum*, *Gaeumannomyces graminis*, *Gibberella f. f. fujikuroi*, *Gloeodes pomigena*, *Gloeosporium musarum*, *Glomerella cingulate*, *Guignardia bidwellii*, *Gymnosporangium juniperi-virginianae*, *Longiformis* species, *Cameloparium* species, *Histoplasma* species (including *Histoplasma capsulatum* (H.)).*Capsulatum*, *Red Line* fungus, *Leptographium lindbergi*, *Leveillula taurica*, *Lophodermium seditiosum*, *Microdochium nivale*, *Microsporum* species, *Sclerotium* species, *Mucor* species, *Cyclophorus* species (including *Cyclophorus gracilis*, *M. pomi*), *Tillandsia* fungus, *Picea* species, *Penicillium* species (including *Penicillium fingernail*, *Penicillium italicum*), *Mycorrhiza* species, *Peronosporium* species (including *Peronosporium fingernail*, *Peronosporium philippinense*, *Peronosporium sorghum*), *Peronosporium* species, *Wheat glume blight*, *Potamogeton crispus*, *Phellinus* *Igiarus*, *Phomopsis*, *Phomopsis viticola*, *Phytophthora* (including pathogenic *Phytophthora*), *Monomophytes* (including *Monomophytes holsae*, *P. viticola*), *Plasmodium*, *P. leucotricha*, *Polymyxa graminis*, *Polymyxa betae*, *Pseudocercosporella herpotrichoides*, *Pseudomonas*, *Pseudomonas* (including *P. cucumberis*, *P. hummus*), *Pseudopeziza tracheiphila*, *P. hordei*, *P. recondita*, *P. styracifolium*. *Striiformis*, *P. triticina*, *Sclerotium* species, *Sclerotium* species, *Pyrhoa* species (including *P. oryzae*), *Pythium* species (including *P. ultimosa*), *Pseudomonas* species, *Rhizomucor pusillus* species, *Rhizomucor pusillus*, *Rhizopus* species, *Rhizopus* species, *S. truncatula* species (including *S. truncatula* and *S. truncatula*), sooty mold (*Schizothyriumpomi*), *Sclerotium* species, *Sclerotium* species, *S. nodorum* species (including *S. nodorum* and *S. truncatula*).The fungi causing powdery mildew include: *Sphaerotheca macularis*, *Sphaerotheca fusca* (*Sphaerotheca fuliginea*), *Sporothorix* species, *Stagonospora nodorum*, *Stemphylium* species, *Stereum hirsutum*, *Thanatephorus cucumeris*, *Thielaviopsis basicola*, *Urocystis* species, *Trichoderma* species (including *Trichoderma harzianum*, *Trichoderma konjac*, and *Trichoderma viride*), *Trichoderma* species, *Sclerotium* species, *Urocystis* species, *Ustilago* species, and *Ustilago* species (including *V. appleis*). *Inaequalis*, species of the genus *Verticillium*, and species of the genus *Xanthomonas*.

[0257] The compounds of formula (I) according to the present invention can be used, for example, for lawns, ornamental plants such as flowers, shrubs, broad-leaved trees or evergreens such as conifers, and tree injection, pest management, etc.

[0258] Within the scope of this invention, the target crops and / or useful plants to be protected typically include perennial and annual crops, such as berry plants, such as blackberries, blueberries, cranberries, raspberries, and strawberries; cereals, such as barley, maize, millet, oats, rice, rye, sorghum, triticale, and wheat; fiber plants, such as cotton, flax, hemp, jute, and sisal; field crops, such as sugar beets and forage beets, coffee beans, hops, mustard, rapeseed (canola), sugarcane, sunflower, tea, and tobacco; fruit trees, such as apples, apricots, avocados, bananas, cherries, citrus fruits, nectarines, peaches, pears, and plums; and grasses, such as Bermuda grass, bluegrass, benjamin grass, centipede grass, yew grass, and rye. Grasses, including St. Augustine and Zoysia japonica; herbs such as basil, borage, chives, coriander, lavender, Angelica pubescens, mint, oregano, parsley, rosemary, sage, and thyme; legumes such as kidney beans, lentils, peas, and soybeans; nuts such as almonds, cashews, peanuts, hazelnuts, peanuts, pecans, pistachios, and walnuts; palm trees such as oil palms; ornamental plants such as flowers, shrubs, and trees; other trees such as cacao, coconut, olive, and rubber trees; vegetables such as asparagus, eggplant, broccoli, cabbage, carrots, cucumbers, garlic, lettuce, zucchini, melons, okra, onions, peppers, potatoes, squash, rhubarb, spinach, and tomatoes; and grapevines such as grapes.

[0259] The term "useful plant" should be understood to also include useful plants that have developed tolerance to herbicides (such as bromonazine) or herbicide classes (such as HPPD inhibitors, ALS inhibitors, such as flusulfuron, fluprosulfuron, and triflusulfuron, EPSPS (5-enol-acetone-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthase) inhibitors, or PPO (protoporphyrinogen oxidase) inhibitors) through conventional breeding methods or genetic engineering. An example of a crop that has been conditioned to tolerate imidazolinones (such as methoxyfenozide) through conventional breeding methods (mutation) is Clearfield® Summer Canola (Canola). Examples of crops that have been conditioned to tolerate herbicides or herbicide classes through genetic engineering include glyphosate-resistant and glufosinate-resistant maize varieties commercially available under the trademarks RoundupReady®, Herculex I®, and LibertyLink®.

[0260] The term “useful plant” should be understood to also include useful plants that have been transformed by the use of recombinant DNA technology to enable them to synthesize one or more selectively acting toxins, such as those known to come from toxin-producing bacteria, especially those of the genus Bacillus.

[0261] Examples of such plants include: YieldGard® (a maize variety expressing CryIA(b) toxin); YieldGardRootworm® (a maize variety expressing CryIIIB(b1) toxin); YieldGard Plus® (a maize variety expressing both CryIA(b) and CryIIIB(b1) toxins); Starlink® (a maize variety expressing Cry9(c) toxin); Herculex I® (a maize variety expressing CryIF(a2) toxin and the enzyme phosphatidinium N-acetyltransferase (PAT) for acquiring tolerance to the herbicide glufosinate); NuCOTN 33B® (a cotton variety expressing CryIA(c) toxin); Bollgard I® (a cotton variety expressing CryIA(c) toxin); Bollgard II® (a cotton variety expressing both CryIA(c) and CryIIA(b) toxins); VICOT® (a cotton variety expressing VIP toxin); NewLeaf® (a potato variety expressing CryIIIA toxin); Nature-Gard® Agrisure® GTAdvantage (GA21 glyphosate-resistant trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait), Agrisure® RW (corn rootworm trait), and Protecta®.

[0262] The term "crop" should be understood to also include crop plants that have been transformed using recombinant DNA technology to enable them to synthesize one or more selectively acting toxins, such as those known to come from toxin-producing bacteria, particularly those of the genus Bacillus.

[0263] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins from *Bacillus cereus* or *Bacillus japonicus*; or insecticidal proteins from *Bacillus thuringiensis*, such as delta-endotoxins, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C, or vegetative insecticidal proteins (Vip), such as Vip1, Vip2, Vip3, or Vip3A; or insecticidal proteins from nematode-parasitic bacteria, such as species of *Photorhabdus* spp. or species of *Xenorhabdus* spp., such as *Photorhabdus luminescens* and *Xenorhabdus*. (nematophilus); toxins produced by animals, such as scorpion venom, spider venom, bee venom, and other insect-specific neurotoxins; toxins produced by fungi, such as streptotoxins; lectins, such as pea lectin, barley lectin, or snowdrop lectin; agglutinin; protease inhibitors, such as trypsin inhibitors, serine inhibitors, potato glycoproteins, cystatin, and papain inhibitors; ribosome-inactivating proteins (RIPs), such as ricin, maize-RIP, absinthecin, loofah seed toxin, saponin toxin, or cassia root toxin; steroid metabolic enzymes, such as 3-hydroxysteroid oxidase, decidual steroid-UDP-glycosyltransferase, cholesterol oxidase, decidualin inhibitors, HMG-COA-reductase, ion channel blockers such as sodium or calcium channel blockers, juvenile hormone esterase, diuretic hormone receptor, stilbene synthase, bibenzyl synthase, chitinase, and glucanase.

[0264] Furthermore, in the context of this invention, δ-endotoxins (e.g., Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C) or vegetative insecticidal proteins (Vip) (e.g., Vip1, Vip2, Vip3, or Vip3A) should be understood to obviously also include mixed toxins, truncated toxins, and modified toxins. Mixed toxins are generated through novel recombination of different combinations of domains of those proteins (see, for example, WO 2002 / 015701). Truncated toxins, such as truncated Cry1Ab, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are substituted. In such amino acid substitutions, it is preferable to insert a non-naturally occurring protease recognition sequence into the toxin, for example, as in the case of Cry3A055, the cathepsin-G-recognition sequence is inserted into the Cry3A toxin (see WO 2003 / 018810).

[0265] Examples of such toxins or genetically modified plants capable of synthesizing such toxins are disclosed, for example, in EP-A-0 374 753, WO 93 / 07278, WO 95 / 34656, EP-A-0 427 529, EP-A-451 878 and WO 2003 / 052073.

[0266] Methods for preparing such transgenic plants are generally known to those skilled in the art and are described in, for example, the disclosures mentioned above. CryI type deoxyribonucleic acid and its preparation are known, for example, from WO 95 / 34656, EP-A-0 367474, EP-A-0 401 979 and WO 90 / 13651.

[0267] The toxins contained in genetically modified plants make them resistant to harmful insects. These insects can exist in any insect taxonomy but are particularly common in beetles (Coleoptera), dipterans (Diptera), and moths (Lepidoptera).

[0268] Transgenic plants containing one or more genes encoding resistance to insecticides and expressing one or more toxins are known, and some of them are commercially available. Examples of such plants include: YieldGard® (a maize variety expressing Cry1Ab toxin); YieldGard Rootworm® (a maize variety expressing Cry3Bb1 toxin); YieldGard Plus® (a maize variety expressing both Cry1Ab and Cry3Bb1 toxins); Starlink® (a maize variety expressing Cry9C toxin); Herculex I® (a maize variety expressing Cry1Fa2 toxin and the enzyme phosphatidylcholine N-acetyltransferase (PAT) for acquiring tolerance to the herbicide glufosinate-ammonium); NuCOTN 33B® (a cotton variety expressing Cry1Ac toxin); Bollgard I® (a cotton variety expressing Cry1Ac toxin); Bollgard II® (a cotton variety expressing Cry1Ac and Cry2Ab toxins); VipCot® (a cotton variety expressing Vip3A and Cry1Ab toxins); NewLeaf® (a potato variety expressing Cry3A toxin); NatureGard® and Agrisure® GT. Advantage (GA21 glyphosate resistance trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait) and Protecta®.

[0269] Other examples of such genetically modified crops are:

[0270] 1. Bt11 maize, from Syngenta Seeds SAS, Chemin del 'Hobit 27, F-31 790 St. Sauveur, France, registration number C / FR / 96 / 05 / 10. A genetically modified maize variety that expresses a truncated Cry1Ab toxin to resist the European corn borer (corn borer and mealybug). Bt11 maize is also genetically modified to express the PAT enzyme to gain tolerance to the herbicide glufosinate.

[0271] 2. Bt176 maize, from Syngenta Seed Company, 27 Hobbit Road, F-31 790 Saint-Soville, France, Registry No. C / FR / 96 / 05 / 10. A genetically modified maize variety that expresses the Cry1Ab toxin transgenically, making it resistant to the European corn borer (corn borer and mealybug). Bt176 maize is also transgenically expressed with PAT enzyme to gain tolerance to the herbicide glufosinate-ammonium.

[0272] 3. MIR604 maize, from Syngenta Seed Company, 27 Hobbit Road, F-31 790 Saint-Soville, France, Registry No. C / FR / 96 / 05 / 10. This is a transgenic maize plant resistant to insects by expressing a modified Cry3A toxin. This toxin is modified by inserting a cathepsin-G-protease recognition sequence, Cry3A055. The preparation of this type of transgenic maize plant is described in WO 2003 / 018810.

[0273] 4. MON 863 maize, from Monsanto Europe SA, 270-272 Avenue de Tervuren, B-1150 Brussels, Belgium, registration number C / DE / 02 / 9. MON 863 expresses Cry3Bb1 toxin and is resistant to certain Coleoptera insects.

[0274] 5. IPC 531 cotton, from Monsanto Europe, 270-272 Teflon Boulevard, B-1150 Brussels, Belgium, registration number C / ES / 96 / 02.

[0275] 6.1507 maize, from Pioneer Overseas Corporation, Avenue Tedesco, 7 B-1160 Brussels, Belgium, Registry No. C / NL / 00 / 10. Genetically modified maize expressing the protein Cry1F to acquire resistance to certain lepidopteran insects and expressing the PAT protein to acquire tolerance to the herbicide glufosinate.

[0276] 7. NK603 × MON 810 maize, from Monsanto Europe, 270-272 Boulevard de Teveren, B 1150 Brussels, Belgium, Registry No. C / GB / 02 / M3 / 03. This hybrid maize variety was created by crossing the genetically modified cultivar NK603 with MON 810, using conventionally bred hybrid maize. NK603 × MON 810 maize transgenically expresses the protein CP4 EPSPS obtained from the Agrobacterium strain CP4, making it resistant to the herbicide Roundup® (containing glyphosate), and also contains the Cry1Ab toxin obtained from Bacillus thuringiensis subsp. Kurstak, making it resistant to certain lepidopteran insects, including the European corn borer.

[0277] The compounds of formula (I) according to the present invention can be used to control or prevent plant pathogenic diseases, particularly plant pathogenic fungi, such as *Alternaria* on fruits, vegetables and potatoes; *Botrytis cinerea* on strawberries, tomatoes, sunflowers, legumes, vegetables and grapes; *Rhizoctonia solani* on potatoes and vegetables; *Uncaria rhynchophylla* on grapes; *Cladosporium*, bryozoans, powdery mildew fungi and *Microcystis cucurbita* on cucurbits; *Botrytis cinerea* nematodes on cucurbits and solanaceous crops; *Fusarium* species on cereals; *Leptosphaeria* species on cereals; and yeast species on cereals.

[0278] As used herein, the term "site" means the place in which or on which a plant grows, or the place where the seeds of a cultivated plant are sown, or the place where the seeds will be placed in the soil. It includes soil, seeds, and seedlings, together with the established vegetation.

[0279] The term "plant" refers to all the tangible parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, culms, leaves, and fruits.

[0280] The term "plant propagation material" should be understood to refer to the reproductive parts of a plant, such as seeds, which can be used for plant propagation, as well as nutrient materials, such as cuttings or tubers (e.g., potatoes). References may include, for example, seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes, and parts of the plant. References may also include germinating plants and young plants that will be transplanted after germination or emergence. These young plants may be protected before transplanting by complete or partial treatment with maceration. Preferably, "plant propagation material" should be understood to refer to seeds.

[0281] The compounds of formula (I) according to the invention can be used in their unmodified form, or preferably, in conjunction with adjuvants conventionally used in the field of formulations. For this purpose, they can be conveniently formulated in known manner as emulsifiable concentrates, coating pastes, directly sprayable or dilutable solutions or suspensions, diluted emulsions, wettable powders, soluble powders, dusts, granules, and also capsules, for example, in polymeric forms. The method of application, such as spraying, atomizing, dusting, spreading, coating, or irrigating, is selected according to the intended purpose and the prevailing environment for the type of composition. The composition may also contain additional adjuvants, such as stabilizers, defoamers, viscosity modifiers, binders, or thickeners, in conjunction with fertilizers, micronutrient donors, or other formulations used to achieve specific effects.

[0282] Suitable carriers and adjuvants, for example, for agricultural use, can be solid or liquid and are substances useful in formulation techniques, such as natural or recycled minerals, solvents, dispersions, wetting agents, thickeners, binders, or fertilizers. Such carriers are described, for example, in WO 97 / 33890.

[0283] Suspension concentrates are aqueous formulations in which finely dispersed solid particles of an active compound are suspended. Such formulations contain anti-settling agents and dispersants, and may further contain wetting agents to enhance activity, as well as antifoamers and crystal growth inhibitors. In use, these concentrates are diluted in water and are typically applied as a spray to the area to be treated. The amount of active ingredient can range from 0.5% to 95% of the concentrate.

[0284] Wettable powders are finely dispersed granules that are easily dispersed in water or other liquid carriers. These granules contain active ingredients retained in a solid matrix. Typical solid matrices include bleaching clay, kaolin, silica, and other easily wettable organic or inorganic solids. Wettable powders typically contain 5% to 95% active ingredient plus small amounts of wetting agents, dispersants, or emulsifiers.

[0285] Emulsifiable concentrates are homogeneous liquid compositions dispersible in water or other liquids and may consist entirely of an active compound and a liquid or solid emulsifier, or may contain a liquid carrier such as xylene, heavy aromatic naphtha, isophorone, and other non-volatile organic solvents. In use, these concentrates are dispersed in water or other liquids and are typically applied as a spray to the area to be treated. The amount of active ingredient can range from 0.5% to 95% of the concentrate.

[0286] Granular formulations consist of both extrudates and coarser granules, and are typically applied undiluted to the area requiring treatment. Typical carriers used in granular formulations include sand, bleaching clay, attapulgite clay, bentonite, montmorillonite, vermiculite, perlite, calcium carbonate, brick, pumice, pyrophyllite, kaolin, dolomite, plaster, wood flour, crushed corn cobs, crushed peanut shells, sugar, sodium chloride, sodium sulfate, sodium silicate, sodium borate, magnesium oxide, mica, iron oxide, zinc oxide, titanium oxide, antimony oxide, cryolite, gypsum, diatomaceous earth, calcium sulfate, and other organic or inorganic materials that absorb or can be coated with active compounds. Granular formulations typically contain 5% to 25% of the active ingredient, which may include surfactants such as heavy aromatic naphtha, kerosene, and other petroleum fractions, or vegetable oils; and / or binders such as dextrin, gum, or synthetic resins.

[0287] Dust powder is a free-flowing mixture of active ingredients and finely dispersed solids (such as talc, clay, flour, and other organic and inorganic solids that serve as dispersants and carriers).

[0288] Microcapsules are typically droplets or particles of active ingredient encapsulated within an inert, porous shell that allows the encapsulated material to escape into the environment at a controlled rate. The diameter of the encapsulated droplets typically ranges from 1 to 50 micrometers. The encapsulated liquid typically constitutes 50% to 95% of the capsule's weight and may contain a solvent in addition to the active compound. The encapsulated particles are typically porous particles, with a porous membrane sealing the particle pores and retaining the active species in liquid form within the pores. The particle diameter typically ranges from 1 millimeter to 1 centimeter, and preferably from 1 millimeter to 2 millimeters. The particles are formed by extrusion, aggregation, or spheroidization, or are naturally occurring. Examples of such materials are vermiculite, sintered clay, kaolin, attapulgite clay, sawdust, and carbon concentrate. Shell or membrane materials include natural and synthetic rubbers, fibrous materials, styrene-butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, and starch xanthates.

[0289] Other useful formulations for agrochemical applications include simple solutions of the active ingredient in solvents such as acetone, alkylated naphthalene, xylene, and other organic solvents, in which the active ingredient is completely dissolved at the desired concentration. Pressurized sprays can also be used, in which the active ingredient is dispersed in a finely dispersed form due to the evaporation of a low-boiling-point dispersant solvent carrier.

[0290] Suitable agricultural adjuvants and carriers useful for formulating the compositions of the present invention among the above-described formulation types are well known to those skilled in the art.

[0291] Suitable liquid carriers include, for example, water, toluene, xylene, naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol rosin ester, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethyl... Formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol (diproxitol), alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glyceryl diacetate, glyceryl monoethyl Ester, glyceryl triacetate, hexadecane, hexanediol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, isopropyl acetone, methoxypropanol, methyl isopentyl ketone, methyl isobutyl ketone, methyl lauryl ketone, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, stearic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol Ingredients include polyethylene glycol (PEG400), propionic acid, propylene glycol, propylene glycol monomethyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin wax, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, methanol, ethanol, isopropanol, and higher molecular weight alcohols (such as pentanol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc.), ethylene glycol, propylene glycol, glycerol, and N-methyl-2-pyrrolidone. Water is typically used as the carrier for diluting the concentrate.

[0292] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, chalk, lime, calcium carbonate, bentonite, bleaching clay, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell powder, and lignin.

[0293] A wide range of surfactants are advantageously used in the liquid and solid compositions, especially those designed to be diluted with a carrier prior to application. These agents typically constitute from 0.1% to 15% of the formulation by weight when used. They can be anionic, cationic, nonionic, or polymeric in nature and can be used as emulsifiers, wetting agents, suspending agents, or for other purposes. Typical surfactants include alkyl sulfates, such as diethanolammonium lauryl sulfate; alkyl aryl sulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol-epoxide addition products, such as nonylphenol-C.sub.18 ethoxylate; alcohol-epoxide addition products, such as tridecyl alcohol-C.sub.16 ethoxylate; soaps, such as sodium stearate; alkyl naphthalene sulfonates, such as sodium dibutylnaphthalene sulfonate; salts of dialkyl sulfosuccinates, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary ammonium chloride, such as lauryltrimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and dialkyl phosphates.

[0294] Other adjuvants commonly used in agricultural compositions include crystallization inhibitors, viscosity modifiers, suspending agents, spray droplet modifiers, pigments, antioxidants, foaming agents, defoamers, opacifiers, compatibility agents, masking agents, neutralizers and buffers, corrosion inhibitors, dyes, flavor enhancers, spreading agents, penetration enhancers, micronutrients, softeners, lubricants, and fixatives.

[0295] Furthermore, other biocidal active ingredients or compositions may be combined with the compositions of the present invention and used in the methods of the present invention, and applied simultaneously or sequentially with the compositions of the present invention. When applied simultaneously, these additional active ingredients may be formulated or mixed together with the compositions of the present invention, for example, in a spray can. These additional biocidal active ingredients may be fungicides, herbicides, insecticides, bactericides, acaricides, nematicides, and / or plant growth regulators.

[0296] The pesticides referred to in this article by their common names are, for example, known from "The Pesticide Manual", 15th edition, British Crop Protection Council 2009.

[0297] Furthermore, the compositions of the present invention can also be administered in combination with one or more systemically acquired resistance inducers (“SAR” inducers). SAR inducers are known and described, for example, in U.S. Patent No. 6,919,298, and include, for example, salicylates and the commercially available SAR inducer aramid-benzene-S-methyl.

[0298] Compounds of formula (I) according to the invention are generally used in the form of agricultural chemical compositions and can be applied simultaneously or sequentially to the crop area or plant to be treated. For example, these additional compounds may be fertilizers or micronutrient donors or other formulations that affect plant growth. They may also be selective or non-selective herbicides, together with insecticides, fungicides, bactericides, nematicides, molluscicides, or mixtures of several of these formulations, and, if desired, with additional carriers, surfactants, or application-promoting adjuvants commonly used in the field of formulations.

[0299] The compounds of formula (I) according to the invention can be used in the form of (fungicide) compositions for controlling or protecting against plant pathogenic microorganisms, the compositions comprising at least one compound of formula (I) as an active ingredient or at least one preferred single compound as defined herein (in free form or in the form of an agrochemically available salt) and at least one of the above-described adjuvants.

[0300] Therefore, the present invention provides a composition comprising at least one compound of formula (I) according to the invention, an agriculturally acceptable carrier, and optionally an adjuvant, preferably a fungicidal composition. An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use. Agricultural carriers are well known in the art. Preferably, in addition to the compound of formula (I), the composition may also comprise at least one or more bioactive compounds, such as additional fungicidal active ingredients.

[0301] The compound of formula (I) according to the invention may be the sole active ingredient of the composition, or, where appropriate, it may be mixed with one or more other active ingredients (such as pest control agents, fungicides, synergists, herbicides, or plant growth regulators). In some cases, the additional active ingredients may produce unexpected synergistic activity.

[0302] Examples of suitable other active ingredients include the following: acycloamino acid fungicides, aliphatic nitrogen fungicides, amide fungicides, aniline fungicides, antibiotic fungicides, aromatic fungicides, arsenic-containing fungicides, arylphenyl ketone fungicides, benzamide fungicides, benzoylaniline fungicides, benzimidazole fungicides, benzothiazole fungicides, phytofungicides, bridged biphenyl fungicides, carbamate fungicides, phenylcarbamate fungicides, conazole fungicides, copper fungicides, diformimide fungicides, dinitrophenol fungicides, dithiocarbamate fungicides, dithiopentane fungicides, furfural amide fungicides, furfuryl aniline fungicides, acylhydrazine fungicides, imidazole fungicides, mercury fungicides, morpholine fungicides, and organophosphate fungicides. Organotin fungicides, oxathiin fungicides, oxazole fungicides, benzylthioamide fungicides, polysulfide fungicides, pyrazole fungicides, pyridine fungicides, pyrimidine fungicides, pyrrole fungicides, quaternary ammonium fungicides, quinoline fungicides, quinone fungicides, quinoxaline fungicides, agaricone fungicides, sulfonanilide fungicides, thiadiazole fungicides, thiazolidine fungicides, thiocarbamate fungicides, thiophene fungicides, triazine fungicides, triazole fungicides, triazolopyrimidine fungicides, urea fungicides, valinamide fungicides, and zinc fungicides.

[0303] The compounds of this invention can also be used in combination with anthelmintic agents. Such anthelmintic agents include compounds selected from macrolides, such as ivermectin, abamectin, emamectin, irinotecan, dolactin, silacritin, moxicritin, nemactin, and milbemycin derivatives, as described in EP 0357460, EP 0444964, and EP0594291. Other anthelmintic agents include semi-synthetic and biosynthetic ivermectin / milbemycin derivatives, such as those described in US 5,015,630, WO 94 / 15944, and WO 95 / 22552. Other anthelmintic agents include benzimidazoles, such as albendazole, canbendazole, fenbendazole, flubendazole, mebendazole, oxifendazole, ocendazole, palbendazole, and other members of this class. Other anthelmintics include imidazothiazoles and tetrahydropyrimidines, such as tetraimidazole, levamisole, pyrantel pamoate, octetil, or molentaxel. Other anthelmintics include trematodes (such as triclofenac and clostridium) and tapeworms (such as praziquantel and estataxel).

[0304] The compounds of the present invention can be used in combination with derivatives and analogs of paraherquamide / marcfortine anthelmintics and antiparasitic oxazolines (such as those disclosed in US 5,478,855, US 4,639,771 and DE-19520936).

[0305] The compounds of the present invention can be used in combination with derivatives and analogs of general types of dioxomorphic antiparasitic agents as described in WO 96 / 15121, as well as with cyclic phenylephrine peptides with anthelmintic activity (such as those described in WO 96 / 11945, WO 93 / 19053, WO93 / 25543, EP 0626375, EP 0382173, WO 94 / 19334, EP 0382173, and EP 0503538).

[0306] The compounds of this invention can be used in combination with other ectoparasite-killing agents; for example, fipronil; pyrethroids; organophosphates; insect growth regulators such as clofenuron; molluscin agonists such as tebufenozide; neonicotinoids such as imidacloprid.

[0307] The compounds of the present invention can be used in combination with terpene alkaloids, such as those described in WO 95 / 19363 or WO 04 / 72086, and especially the compounds disclosed therein.

[0308] Other examples of such bioactive compounds that can be used in combination with the compounds of the present invention include, but are not limited to, the following:

[0309] Organophosphates: Acetaminophen, Methylpyridinium phosphate, Ethyl glutathione, Methyl glutathione, Bromothione, Ethyl Bromothione, Thiophanate, Chlorethoxyphos, Chlorpyrifos, Chlorfenapyr, Demeton-methyl, Demeton-S-methyl sulfone, Chlorimide, Diazinon, Dichlorvos, Phosphate, Dimethoate, Ethiophanate-methyl, Ethiophanate-methyl, Ethiophanate-methyl, Oxypyridazine, Valdex, Benzophos, Fenitrothion, Fonsophos, Fenthion, Pyralidoxime, Terbufos, Ango, Thiazolephos, Heptenphos, Chlorpyrifos, Isoprophos, Isoxazolphos, Malathion Phosphorus, chlorfenapyr, methamidophos, chlorpyrifos, methyl parathion, methamidophos, phosmet, dibromophos, omethoate, methyl oxyphosphazene, paraoxon, parathion, methyl parathion, phosmet, phosmet, phosmet, phosmet, phosmet, phorate, phorate, phoxim, chlorfenapyr, chlorfenapyr-methyl, profenofos, profenofos, proetamphos, pyrazophos, pyridazinphos, quinalphos, thiophanate-methyl, tebufenozide, terbufos, butylpyrimidine phosphate, stiotronazine, thimeton, triazophos, trichlorfon, chlorpyrifos.

[0310] Carbamates: Carbofuran, Aldicarb, 2-sec-butylphenylmethylcarbamate, Propylene carbofuran, Carbofuran, Butyl carbofuran, Dichlorvos, Ethylbenzylcarbide, Phenoxycarbide, Fenthiocarb, Furazolidone, HCN-801, Isopropylcarbide, Indomethacin, Methomyl, 5-Methyl-m-isopropylphenylbutynyl (methyl)carbamate, Apimethoate, Pyriproxyfen, Prochloraz, Thiamethoxam, Dichlorvos, Apimethoate, UC-51717.

[0311] Pyrethroids: Flufenoxuron, Propyrethrin, Alphametrin, 5-Benzyl-3-furanylmethyl(E)-(1R)-cis-2,2-dimethyl-3-(2-oxothiacyclopentan-3-ylidenemethyl)cyclopropanecarboxylate, Bifenthrin, β-Cypermethrin, Flufenoxuron, α-Cypermethrin, β-Cypermethrin, Bioallethrin, Bioallethrin ((S)-cyclopentyl isomer), Biobenzylfuran, Bifenthrin, NCI-85193, Pyrethroids Pyrethrin, deltamethrin, cythithrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin (D isomer), deltamethrin, deltamethrin, λ-deltamethrin, permethrin, deltamethrin, deltamethrin, pyrethrin (natural product), deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin, deltamethrin.

[0312] Arthropod growth regulators: a) Chitosan synthesis inhibitors: Benzoylurea: diflubenzuron, chlorfenapyr, pyridaben, flufenoxuron, flufenoxuron, flufenuron, chlorfenuron, difenofuron, fenflurfen, chlorfenapyr, thiamethoxam, bensulfuron, thiamethoxam, etoxazole, chlorfenapyr; b) Decacitonin antagonists: chlorfenapyr, methoxyfenozide, tebufenozide; c) Juvenile hormone analogs: pyriproxyfen, tebufenozide (including S-tebufenozide), phenoxycarb; d) Lipid biosynthesis inhibitors: spirodiclofen.

[0313] Other antiparasitic drugs: Acaricide, Amitraz, AKD-1022, ANS-118, Azadirachtin, Bacillus thuringiensis, Cypermethrin, Bifenazate, Acaricide, Bromopropylate, BTG-504, BTG-505, Toxaphene, Mefenoxam, Difenoconazole, Acaricide, Bromnifloxacin, Cyclodinafop-methyl, Thiamethoxam, Dimethomorph, Dicloden, Acaricide, DBI-3204, Dichlorophenoxyacetic acid, Dihydroxybenzene Methyl dihydroxypyrrolidine, fenpyroximate, fenpyroximate, endosulfan, acetamiprid, permethrin, quinclorac, flumite, MTI-800, azoxystrobin, pyrimethanil, flufenoxuron, deltamethrin, flufenoxuron, trifluralin, fluproxyfen, halofenprox, flufenoxuron, IKI-220, sodium silicate, NC-196, Indian mint (neem) guard), nidinorterfuran, acetamiprid, SD-35651, WL-108477, acetamiprid, clopyralid, protrifenbute, pymetrozine, pyridaben, pyrimethanil, NC-1111, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, flusilyl ester, silomadine, spinosad, pymetrozine, trichlorfon, tetracycline, thiamethoxam, chlorpyrifos, thiamethoxam, azoxystrobin, pymetrozine, spinosad, trichlorfon, synergistic acetylacetonate, vertalec, YI-5301.

[0314] Biological agents: Bacillus thuringiensis ssp. aizawai, Bacillus spp. Kurstaki, Bacillus thuringiensis δ endotoxin, baculoviruses, entomopathogenic bacteria, viruses and fungi.

[0315] Bactericides: chlortetracycline, oxytetracycline, streptomycin.

[0316] Other biological agents: Enflufloxacin, febantal, pentxacillin, meloxicam, cephalexin, kanamycin, pimoxendan, clenbuterol, omeprazole, tiamulin, benazepril, pyriprole, cefoquinol, florfenicol, buserelin, cefotaxime, tolazoline, ceftiofur, carbofenoxuron, meflurane, praziquantel, triclobenzazole.

[0317] The following mixtures of compounds having formula (I) and active ingredients are preferred. The abbreviation "TX" refers to a compound selected from the group consisting of compounds having the formula (I), (II), (III), or (III-A), or a compound selected from the group consisting of compounds listed in Tables C-1 to C-60 or Table P (hereinafter); and a compound selected from the group consisting of: (4E,10Z)-tetradecano-4,10-dienyl acetate + TX; (7E,9Z)-dodecano-7,9-dien-1-yl acetate + TX; (E)-6-methylhept-2-en-4-ol + TX; (E)-decano-5-en-1-yl acetate and (E)-decano-5-en-1-ol + TX; (E)-tetrate-4-en-1-yl acetate + TX; (S)-bioallethrin + TX; (Z)-dodecano-7-en-1-yl acetate + TX; (Z)-hexadecano-11-en-1-yl acetate + TX; TX; (Z)-hexadec-11-enal + TX; (Z)-hexadec-13-en-11-yn-1-yl acetate + TX; (Z)-eicos-13-en-10-one + TX; (Z)-tetradec-7-en-1-al + TX; (Z)-tetradec-9-en-1-ol + TX; (Z)-tetradec-9-en-1-yl acetate + TX; 1,1-bis(4-chlorophenyl)-2-ethoxyethanol + TX; 1-(2-chlorophenyl)-3,3-dimethyl-2-(1,2,4-triazol-1-ylmethyl)but-2-ol + TX; 1-(5-bromo-2-pyridyl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1,2,4-triazol-1-yl)prop-2-ol + TX; 1-H-hydroxy-1H-pyridine-2-thione + TX; 1-methylcyclopropene + TX; 1-naphthylacetamide + TX; 1-naphthylacetic acid + TX; 2,2-dichlorovinyl-2-ethylsulfinyl ethyl methyl phosphate + TX; 2,4-D + TX; 2,4-DB + TX; 2,6-dichloro-N-(4-trifluoromethylbenzyl)benzamide + TX; 2-(1,3-dithiopentane-2-yl)phenyl dimethyl carbamate + TX; 2-(2-butoxyethoxy)ethyl piperate + TX; 2-(4,5-dimethyl-1,3-dioxolane-2-yl)phenyl methyl carbamate + TX; 2-(difluoromethyl)-N-((3R)-1,1,3-trimethylindan-4-yl)pyridine-3-carboxamide + TX; 2-(octylthio)-ethanol + TX; 2-bromo-2-bromomethylglutaronitrile + TX; 2-chlorovinyl diethyl phosphate + TX; 2-imidazolinone + TX; 2-methyl(prop-2-ynyl)aminophenyl methyl carbamate + TX;2-Cyanothioylethyl Laurate + TX; 3-(4-Chlorophenyl)-5-methylrhodanine + TX; 3-(difluoromethyl)-1-methyl-N-[1,1,3-trimethylindane-4-yl]pyrazole-4-carboxamide + TX; 3-(difluoromethyl)-N-(7-fluoro-1,1,3,3-tetramethyl-indane-4-yl)-1-methyl-pyrazole-4-carboxamide + TX; 3-(difluoromethyl)-N-(7-fluoro-1,1,3,3-tetramethyl-indane-4-yl)-1-methyl-pyrazole-4-carboxamide + TX; 3-chloro-6-methyl-5-phenyl-4-(2,4,6-trifluorophenyl)pyridazine + TX; 3-methyl-1-phenylpyrazole-5-yldimethylcarbamate + TX; 3-phenylphenol + TX; 4,5-Dichlorodithiol-3-one + TX; 4-(2,6-difluorophenyl)-6-methyl-5-phenyl-pyridazin-3-carboxylonite + TX; 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-2,5-dimethyl-pyrazole-3-amine + TX; 4-(quinoxaloline-2-ylamino)benzenesulfonamide + TX; 4-[[6-[2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile + TX; 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazin-3-one + TX; 4-CPA + TX; 4-Methyl(prop-2-ynyl)amino-3,5-dimethylmethylcarbamate + TX; 4-Methylnon-5-ol and 4-methylnon-5-one + TX; 4-Phenylenol + TX; 5-(1,3-benzodioxane-5-yl)-3-hexylcyclohex-2-enone + TX; 5-amino-1,3,4-thiadiazol-2-thiol + TX; 5-fluoro-2-(p-tolylmethoxy)pyrimidin-4-amine + TX; 5-hydroxy-6-methyl-4-(((E)-pyridin-3-ylmethylene)amino)-4,5-dihydro-1,2,4-triazine-3(2H)-one + TX; 5-methyl-6-thio-1,3,5-thiadiazine-3-ylacetic acid + TX; 8-hydroxyquinoline sulfate + TX; 11-Ethyl-10,12-dioxo-2,5,8-trithia-4,11-diazatricyclo[7.3.0.03,7]dodec-1(9),3,6-trien-6-carboxynitrile + TX; 14-Methyloctadec-1-ene + TX; [(9Z,11E)-tetradec-9,11-dienyl]acetate + TX; [(Z)-dodec-9-enyl]acetate + TX; abamectin + TX; acephate + TX; miticide + TX; acetamiprid + TX; aspartame + TX;Acetaminophen + TX; Aramacin + TX; Aramacin-S-methyl + TX; Flufenoxuron + TX; Cotton Brown Leaf Roller GV + TX; *Agrobacterium radiata* + TX; Cotton Bollworm + TX; Albendazole + TX; Aldicarb + TX; Propyrethroid + TX; Alpromethazine + TX; Allyl alcohol + TX; Dimethomorph + TX; α-Decidulin + TX; α-Polycarb + TX; *Amblyseius* spp. + TX; Azoxystrobin + TX; Cypermethrin + TX; Sulfamethrin + TX; Phosphamidon + TX; Mefenoxam + TX; Indoxam + TX; Ammonium phosphate + TX; Ammonium phosphate oxalate + TX; Amitraz + TX; Neonicotinic acid + TX; Celery Earworm NPV + TX; *Anagrus* atomus + TX; pyrimidinol + TX; difenoconazole + TX; anisiflupurin + TX; anthraquinone + TX; antagonist + TX; short-spurred aphid wasp + TX; cotton aphid parasitic wasp (Aphidiuscolemani) + TX; aphid gall midge (Aphidoletes aphidimyza) + TX; ethyl chlorpyrifos + TX; golden nystatin + TX; alfalfa silver-striped moth NPV + TX; abamectin B1a + TX; azaconazole + TX; azadirachtin A + TX; pyrazosulfuron + TX; methyl pyridaben + TX; ethyl glutathione + TX; methyl glutathione + TX; thiram + TX; azoxystrobin + TX; Bacillus sphaericus Neide + TX; Bacillus thuringiensis + TX; Bacillus thuringiensis δ-endotoxin + TX; Bacillus thuringiensis subsp. niger + TX; Baculovirus + TX; Pyrethroid + TX; Beauveria brongniartii + TX; Benzophenone + TX; Benzophenone + TX; Benazepam + TX; Benzophenone + TX; Benzoate + TX; Benzoate + TX; Sulfonamide + TX; Benzalkonium chloride + TX; Phytoprofen + TX; Benzac + TX; Benzopyr + TX; Benzoate + TX; Benzofenazate + TX; β-Cypermethrin + TX; β-Cypermethrin + TX; Bethoxazin + TX; Bifenazate + TX; Bifenthrin + TX; Acaricide + TX; Bioallyl + TX TX; bioethanomethrin + TX;Biological permethrin + TX; Biological benzylfuran + TX; Diflubenzuron + TX; Diflubenzuron + TX; Bifenthrin + TX; Bifenazate + TX; Isopyram S + TX; Borax + TX; Bordeaux mixture + TX; Boscalid + TX; Bromadioxanil + TX; Bromocypermethrin + TX; Bromofenopterin + TX; Bromophos + TX; Bromophos-ethyl + TX; Fenoxacrylamide + TX; Dichlorvos + TX; Bupirimate + TX; Thiazide + TX; Buserelin + TX; N-[6-[[(Z)-[(1-methyltetrazole-5-yl)-phenyl-methylene]amino]oxymethyl]-2-pyridyl]carbamate butyl-3-yne ester + TX; Carbofuran + TX; Terpyrimethanil + TX; Butanyl ketone + TX; Butyl ester + TX; DEET + TX; Butoxyl (polypropylene glycol) + TX; Butanyl ketone sulfonate + TX; Butylamine + TX; Thiophanate + TX; Calciferol + TX; Calcium phosphate + TX; Calcium polysulfide + TX; Canbendazole + TX; Captan + TX; Captan + TX; Chlorfenapyr + TX; Carbaryl + TX; Carbendazim + TX; Carbendazim Hydrochloride + TX; Carbofuran + TX; Thiocarbofuran + TX; Car ... TX; Cevadine + TX; Acaricide + TX; Chitosan + TX; Chlorpheniramine + TX; Chloralose + TX; Chlorantraniliprole + TX; Acaricide + TX; Amitraz + TX; Ethephon + TX; Phosphorus oxychloride + TX; Brofennig + TX; Chlorfenazole + TX; Tetramethrin + TX; Chlorfenapyr + TX; Difenoconazole + TX; Chlormethoate + TX; Chlormequat + TX; Chlormequat + TX; Chlorpyrifos + TX; Chlorpyrifos + TX; Chlorpyrifos-methyl + TX; Chlortetracycline + TX; Chlormethoate + TX; Ethiophanate-methyl + TX; Cholecalciferol + TX TX; Cyclofenac + TX; Chrysoperla carnea + TX; Cucurbitacin + TX; Cucurbitacin I + TX;Ciprofloxacin II + TX; cis-jasmone + TX; cis-resmethrin + TX; cismethrin + TX; clenbuterol + TX; glycyrrhizin + TX; terbufos + TX; benzimidazin + TX; clostridium + TX; thiamethoxam + TX; clozylacon (acetamide) + TX; codlelure + TX; copper acetate + TX; copper hydroxide + TX; copper naphthenate + TX; copper octanoate + TX; copper oleate + TX; copper oxide + TX; copper oxychloride + TX; copper silicate + TX; copper sulfate + TX; copper(II) carbonate + TX; chlorpyrifos + TX; coumafene + TX; chlorpyrifos + TX; coumethoxystrobin + TX; jiaxiangjunzhi + TX TX; Phosphate + TX; Hydatid + TX; Cryolite + TX; Cryptolaemus montrouzieri + TX; Fly attractant + TX; Thiazol + TX; Cuprous oxide (I) + TX; Benzoate + TX; Folic acid + TX; Cymoxanil + TX; Cybutyr + TX; Furazolidone + TX; Pyrethrum + TX; Trifluralin + TX; Codling moth GV + TX; Cyprodinil + TX; Cyclofenac + TX; Fenoxyfen + TX; Diflubenzuron + TX; Cyfluthrin + TX; Trifluralin + TX; Acaricide + TX; Cymoxanil + TX; Cypermethrin + TX; Cypermethrin + TX; Cypermethrin + TX; Cypermethrin + TX TX; Cymoxanil + TX; Cytokinin + TX; D-methrin + TX; Siberian pyrethroid wasp + TX; DAEP + TX; Dazomet + TX; DCPM + TX; Imazalil + TX; Decarbofuran + TX; Delmethrin + TX; Phosphate-O + TX; Phosphate-S + TX; Demeton-O + TX; Demeton-S + TX; Demeton-S-methyl + TX; Demeton-S-methyl sulfone + TX; Acaricide + TX; Chlorpyrifos + TX; Diazinon + TX; Dibutyl adipate + TX; Dibutyl phthalate + TX; Dibutyl succinate + TX; Isochlorpyrifos + TX; Dichlorophenoxyacetate + TX; Dichloronaphthoquinone + TX; 2,4-D propionic acid + TX; Dichlorvos + TX; Sclerotinia + TX;Diclofenac + TX; Pyridaben + TX; Chlornitramine + TX; Trichlorfon + TX; Didicresyl + TX; Phosphate + TX; Desminol + TX; Dicyclopentadiene + TX; Ethiocarb + TX; DEET + TX; Dimethoate + TX; Difenoconazole + TX; Wild Bean Fly + TX; Thiamethoxam + TX; Flufenoxuron + TX; Diflubenzuron + TX; Flupyridamole + TX; Pea Leafminer Wasp + TX; Dimatif + TX; Tetrafluorometholone + TX; Dimethoate + TX; Iprodione + TX; Thiamethoxam + TX; Dimethoate + TX; Dimethoate + TX; Dimethyl Disulfide + TX; Dimethyl Phthalate + TX TX; Difenoconazole + TX; Azoxystrobin + TX; Difenoconazole + TX; Tebuconazole + TX; Zimbaben + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Difenoconazole + TX; Dithiocarbamate + TX; Dodecano-8-en-1-ylacetate + TX; Dodecylmorpholine + TX; Dodecyl + TX; Doxorubicin + TX; Dofenapyn + TX; Dominicalure + TX; Doxorubicin + TX; Difenoconazole + TX; DSP + TX; Ecstatone + TX; Kebensan + TX; Emafenac benzoate + TX; EMPC + TX; Dextromethorphan + TX; Encarsia formosa + TX; Endothiocyanate + TX; Herbadox + TX; Indomethacin + TX; Enstroburin (enoxastrobin) + TX; Enrofloxacin + TX; Insect pathogenic bacteria + TX; Insect pathogenic fungi + TX; Insect pathogenic viruses + TX; EPBP + TX; Flutriafol + TX; Irinocinol + TX; Eretmocerus eremicus + TX; Cypermethrin + TX; Ethiconazole + TX; Ethaclopramide + TX; Ethiophanate-methyl + TX; Ethiophanate + TX; Ethirimol +TX; Beneficial Sulfur Phosphorus + TX;Phosphate + TX; Ethoxyquin + TX; Ethyl 4-methyloctanoate + TX; Ethyl formate + TX; Ethylhexane glycol + TX; Permethrin + TX; Etoxazole + TX; Chlorpyrifos + TX; Ethiophanate + TX; Eugenol + TX; Eurax + TX; EXD + TX; Exo-brevicomin + TX; Oxafloxacin + TX; Valproic acid + TX; Farnesol and Nerolidol + TX; Fibentel + TX; Imidacloprid + TX; Enoxaflutole + TX; Benzyl + TX; Chlorpyrimethanil + TX; Quinalox + TX; Fenbendazole + TX; Cyproconazole + TX; Fenbutanol + TX; Quinoline + TX; Ethylcarbamide + TX; Pyrimethanil + TX; Mefenoxam + TX TX; Cyclopyralid + TX; Fenitrothion + TX; Butyral + TX; Difenoconazole + TX; Benthiocarb + TX; Oxypyrimamide + TX; Isoprothiolane + TX; Fenoxycarb + TX; Seed dressing + TX; Phenylopyramide + TX; Cypermethrin + TX; Cypermethrin + TX; Benzoyl + TX; Butazoline + TX; Amifenopyram + TX; Azoxystrobin + TX; Fusoxin + TX; Fenthion + TX; Ethyl Fenthion + TX; Triphenyltin + TX; Triphenyltin Acetate + TX; Triphenyltin Chloride + TX; Triphenyltin Hydroxide + TX; Cypermethrin + TX; Ferrous Sulfate + TX; Azoxystrobin + TX; Ferric Phosphate + TX; Fipronil + TX; Flufenoxuron + TX; Flufenoxuron + TX; Pyridaben + TX TX; Pyrimethanil + TX; Fluazinam + TX; Acetobacter + TX; Flubendazole + TX; Flufenoxuron + TX; Flufenoxuron + TX; Flufenoxuron + TX; Flufenoxuron + TX; Cypermethrin + TX; Fludioxonil + TX; Biflufenoxuron + TX; Pyrimethanil + TX; Flufenoxuron ... TX; Fluoroamide + TX; Tebuconazole + TX; Fluopyram + TX; Captan + TX; Dichlorvos + TX; Chlorpyrifos + TX; Formaldehyde + TX;Amitraz + TX; Amitraz Hydrochloride + TX; Anorthoxyfen + TX; Algaecide + TX; Fosetyl-aluminium + TX; Butazophos + TX; Thiazolylphosphonate + TX; Butanethion + TX; Southern pine bark beetle pheromone + TX; Erythrin + TX; Furazolidone + TX; Furazolidone + TX; Furazolidone + TX; Pyrethrum + TX; Furfural + TX; Gibberellin + TX; Glyphosate + TX; Enthalpyrethroid I + TX; Enthalpyrethroid II + TX; Enthalpyrethroid III + TX; Enthalpyrethroid IV + TX; Biguanidin Triacetate + TX; Benzylfentanyl + TX; Chlorfenapyr + TX; Hexamethonium + TX; Hepten + TX; Heterorhabditis bacteriophora and H. megidis + TX; Hexaconazole + TX; Cetylcyclopropane carboxylate + TX; Flufenoxuron + TX; Hexamide + TX; Thiamethoxam + TX; Hippodamia convergens + TX; Huanjunzuo (racemic-(1S,2S)-1-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)cycloheptanol) + TX; Flufenoxuron + TX; Quicklime (calcium hydroxide) + TX; Hymexazol + TX; Quinoline + TX; Icaridin + TX; Hypericin + TX; Imazalil + TX; Imazalil sulfate + TX; Imidazole + TX; Imidacloprid + TX; Biguanidine Octylamine + TX; Indoxacarb + TX; Indopyramide + TX; Iodocarb + TX; Succinazole + TX; Ifentriconazole + TX; Iprodione + TX; Isoprothiolane (IBP) + TX; Iprodione + TX; Valproic acid + TX; Ipsdienol + TX; Ipssenol + TX; IPSP + TX; Isamidophos + TX; Chlorpyrifos + TX; Methionine + TX; Iprodione + TX; Iprodione + Fluopyram + TX; Transplanting agent + TX; Iprodione + TX; Isoprothiolane + TX; Pyrazothiamethoxam + TX; Iprodione + TX; Iprodione + TX; Isoxazol + TX TX; Ivermectin + TX; Scarab beetle sex pheromone + TX; Jasminate I + TX; Jasminate II + TX; Juvenile hormone I + TX; Juvenile hormone II + TX;Juvenile hormone III + TX; thiamethoxam + TX; kanamycin + TX; kasugamycin + TX; kasugamycin hydrochloride hydrate + TX; kinetin + TX; acetamiprid + TX; azoxystrobin + TX; Bacillus spp. Kurstak + TX; lambda-cyhalothrin + TX; Leptomastix dactylopii + TX; parathion + TX; levamisole + TX; lineatin + TX; acetamiprid + TX; pheromone for the white spot moth + TX; clofenuron + TX; lvbenmixianan + TX; thiazophos + TX; m-isopropylphenyl methylcarbamate + TX; mirid bug (Macrolophus caliginosus) + TX; magnesium phosphide + TX; malathion + TX; maleic hydrazine + TX; Profenofibrate + TX; Cabbage looper NPV + TX; Mancozeb + TX; Mancozeb + TX; Toluene + TX; Dimethomorph + TX; Mancozeb + TX; Azoxystrobin + TX; Mebendazole + TX; Phosphamidon + TX; Tetramethrin + TX; Acetylpyridinium + TX; Chlorfenapyr + TX; Megacodone + TX; Meloxiconazole + TX; Apimethomorph + TX; Cypermethrin + TX; Dithiophos + TX; Mepiquat chloride + TX; Acaricide + TX; Fenoxacin + TX; Mefenoxam + TX; Metalaxyl + TX; Metalaxyl + TX; Methionol + TX; Methionol-potassium + TX; Methionol-sodium + TX; Metaphycus helvolus) + TX; Metarhizium anisopliae var. acridum + TX; Metarhizium anisopliae var. anisopliae + TX; Pyroxim + TX; Tebuconazole + TX; Chlorpyrifos + TX; Methamidophos + TX; Sulpharophos + TX; Phoxim + TX; Thiamethoxam + TX; Thiophanate + TX; Thiophanate + TX; Ethylphosphide + TX; Methomyl + TX; Methoxyfen + TX; Methoxyfen + TX; Methoxyfen + TX; Methyl apholate + TX; Methyl eugenol + TX; Iodoform + TX; Methyl neodecanoamide + TX; Mancozeb + TX;Methoxyfenozide + TX; Dimethoate + TX; Fenoxynil + TX; Imidacloprid + TX; Benomyl + TX; Tetracycline + TX; Mefenoxam + TX; Zicocarb + TX; MGK 264 + TX; Milbemycin + TX; Milbexime + TX; Phosphorus + TX; Morentyl tartrate + TX; Morzid + TX; Moxifloxacin + TX; muscalure + TX; Cyproconazole + TX; Myclozolin + TX; Varicella spp. composition + TX; N-[2-[2,4-dichloro-phenoxy]phenyl]-3-(difluoromethyl)-1-methyl-pyrazole-4-carboxamide + TX; N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-[(2-isopropylphenyl)methyl]-1-methyl-pyrazole-4-carboxamide + TX; Sodium mancozeb + TX; Dibromophos + TX; NC-170 + TX; Nemoxybenzone + TX; Neodiprion sertifer NPV and N. lecontei NPV + TX; Nitrosamide-ethanolamine + TX; Nicotine + TX; Nicotine sulfate + TX; Nicotinamide + TX; Acetaminophen + TX; Niethoxythiazole + TX; Chloridine + TX; Cypermethrin + TX; Phthalosporin + TX; Sodium thiosulfate + TX; Nornicotinamide + TX; Fluorouracil + TX; Polyfluorourea + TX; Fluoropyrimidine + TX; O,O,O',O'-Tetrapropyldithiopyrophosphate + TX; Octadecto-2,13-dien-1-yl acetate + TX; Octadecto-2,13-dien-1-yl acetate + TX; Octathione + TX; Furosemide + TX; Oleic acid + TX; Omethoate + TX; Orfralure + TX; Small-flowered bug species + TX; Oximethiophene + TX; Osthol + TX; Ostramone + TX; Oxysulfuron + TX; Oxamate + TX; Cadaverine + TX; Dihydroxynaphthyl acetonide + TX; Pyrimethanil + TX; Fluoxetine + TX; Olfendazole + TX; Oxendazole + TX; Quinoline copper + TX; Oxadiazine + TX; Oxazolol + TX; Oxysulforil + TX; Methyloxophosphorus + TX; Isofenphos + TX; sulfone phosphate + TX; oxytetracycline + TX; oxytetracycline dihydrate + TX; paclobutrazol + TX; *Paecilomyces roximate* + TX; paraoxon + TX; parathion + TX; methyl parathion + TX; parbendazole + TX; isoprothiolane + TX;Pendimethalin + TX; Pendimethalin + TX; Pensacillin + TX; Fluopyram + TX; Pyraclostrobin + TX; Permethrin + TX; Petroleum + TX; pH 60-38 + TX; Cyazofamid + TX; Indomethacin + TX; Phenyphorate + TX; Ratphos + TX; Phosphamidon + TX; Thiophanate + TX; Glyphosate + TX; Aminophazine + TX; Chlorpyrifos + TX; Phosphamidon + TX; Fipronil + TX; Phosphamidon + TX; Phosphamidon + TX; Phosphamidon + TX; Phosphamidon + TX; Phosphamidon + TX; Phytoseiulus persimilis + TX; Picarbutrazox + TX; Azoxystrobin + TX; Pimobendan + TX; Warfarin + TX; Piperaldehyde + TX; Piperyl Butyl Ether + TX TX; Synergistic Aldehyde + TX; Methamidophos + TX; Pirimicarb + TX; Methylpyrimidine + TX; Polycarbamate + TX; Naphthylmethoxam + TX; Polyoxin B + TX; Polyoxin D + TX; Potassium Ethyl Xanthate + TX; Potassium Hydroxyquinoline Sulfate + TX; Praziquantel + TX; Precozid I + TX; Precozid II + TX; Precozid III + TX; Aminopyrimidine + TX; Thiamethoxam + TX; Prochloraz + TX; Profenofos + TX; Profenofos + TX; Profenofos + TX; Prop ... TX; Procymidone + TX; Propropyl isomer + TX; Proquinazid + TX; Ethiazophos + TX; Prothioconazole + TX; Prothioconazole + TX; Folic acid + TX; Profenbutatin + TX; Fluopyram + TX; Pymetrozine + TX; Pyrazophos + TX; Azoxystrobin + TX; Pyrazophos + TX; Azoxystrobin + TX; Dimethoate + TX; Azoxystrobin + TX; Pyridaben + TX; Bifenazate + TX; Dimethoate + TX; Pyrazinone + TX; Pyrethroid + TX; Pyrethroid I + TX; Pyrethroid II + TX; Pyrethroid (natural product) + TX; Pyrethroid (natural product) + TX; Pyraclostrobin + TX; Pyridaben + TX; Fluopyram + TX TX; Acetaminophen + TX; Pyridazine + TX; Pyridine-4-amine + TX; Pyridabenoxime + TX;Flufenoxam + TX; Pyrimethanil + TX; Pyrimethanil + TX; Pyrmethrin + TX; Phenythiophanate-methyl + TX; Piriton + TX; Piriprofen + TX; Pyriproxyfen + TX; Pyrimethanil + TX; Pyrimethanil + TX; Magnolia officinalis extract + TX; Quinoline + TX; Quinoline-methyl + TX; Alginate + TX; Quinoline + TX; Quinoline + TX; Quinoline + TX; Quinoline + TX; Quinoline + TX; Quinoline + TX; Pentachloronitrobenzene + TX; R-1492 + TX; R-Methoxyfen + TX; Polygonum cuspidatum extract + TX; Ribavirin + TX; Rotenone + TX; Raniline + TX; Raniline + TX; Veratrum saba + TX; Octylphosphatase + TX; Onyx glycoside + TX; Cymoxanil + TX; Fluoxetine + TX; Silaclofen + TX; Synergistic powder + TX; Sesamol + TX; Insect attractant + TX; Flumethrin + TX; Silthiamethoxam + TX; Silomethoxam + TX; Sodium tetrathiocarbonate + TX; Thresh + TX; Sordidin + TX; Ethyl spinosad + TX; Spinosad + TX; Spirodiclofen + TX; Spirodiclofen + TX; Spirotetramethrin + TX; Spirocyclohexyl + TX; Steinernema bibionis + TX; Steinernema carpocapsae + TX; Steinernema noctuid + TX; Steinernema glaseri + TX; Steinernema riobrave + TX; Steinernema riobravis + TX; Steinernema mole cricket + TX scapterisci) + TX; scapteris species + TX; streptomycin + TX; streptomycin sesquisulfate + TX; methamidophos + TX; sulfadiazine + TX; sulfamethoxam + TX; sulfur + TX; thiophanate-methyl + TX; tar + TX; t-flumethrin + TX; TCMTB + TX; TDE + TX; tebuconazole + TX; tebufenozide + TX; pyridaben + TX; isobutylethoxyquin + TX; butylpyrimidine + TX; tetrachloronitrobenzene + TX; flufenoxuron + TX; heptafluthrin + TX; dithion + TX; cyclopentadiazine + TX; terbufos + TX; terbufos + TX; chlorpyrifos + TX; tetrafluoroethylene + TX; tetradecyl-11-en-1-ylacetate + TX; tetrachlorfon + TX; pyrethroid + TX TX; Tetrafluoroethylene + TX; Acaricide + TX;Thiabendazole + TX; Thiamethoxam + TX; Thiadiazon + TX; Thiamethoxam + TX; Thiamethoxam + TX; Thiamethoxam + TX; Thiamethoxam + TX; Thiamethoxam + TX; Thifluzamide + TX; Carbendazim + TX; Cypermethrin + TX; Cypermethrin Oxyxamate + TX; Thiamethoxam + TX; Dimethoate + TX; Thiamethoxam + TX; Thiamethoxam + TX; Thiamethoxam + TX; Acaricide + TX; Dimethoate + TX; Dimethoate-Disodium + TX; Thiamethoxam + TX; Thiamethoxam + TX; Tiamulin + TX; Tioxymid + TX; Methyl Litharge + TX; Azoxystrobin + TX; Trifluthoxycarb + TX; Paramethoprim + TX; Tetrabromopropylate + TX; Transchlorophenate + TX TX; Tratamide + TX; Triadimefon + TX; Triadimefon + TX; Benfenthiamethoxam + TX; Azoxystrobin + TX; Triazophos + TX; Imidazin + TX; Defoliant + TX; Trichlorfon + TX; Isofenphos-3 + TX; Phosphorus + TX; Trichogramma + TX; Trichlorophenazine + TX; Tricyclazole + TX; Tridemorph + TX; Snailicide + TX; Azoxystrobin + TX; Fluopyram + TX; Cyclofenac + TX; Azoxystrobin + TX; Mediterranean fruit fly attractant + TX; Mediterranean fruit fly attractant A + TX; Mediterranean fruit fly attractant B1 + TX; Mediterranean fruit fly attractant B2 + TX; Mediterranean fruit fly attractant C + TX; Mixed carbendazim + TX; Trichloroisocyanuric acid + TX; Anti-rot ester + TX; Anti-rot ester-ethyl + TX TX; tebufenozide + TX; methamidophos + TX; trunc-call + TX; torazom + TX; Typhlodromus occidentalis + TX; uniconazole + TX; urethaneimine + TX; siloxane + TX; valhalamine + TX; abamectin + TX; fipronil + TX; veratrine + TX; veratrine + TX; synergistic alkyne + TX; Verticillium lecanii + TX; vinclozolin + TX; XMC + TX; xylenol + TX; zeatin + TX; ζ-cypermethrin + TX; kasugamycin + TX; zinc naphthenate + TX; zinc thiamethoxam + TX; zineb + ​​TX; thiram + TX; pyraclostrobin + TX; benzoylmide + TX;2-(difluoromethyl)-N-[(3S)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide (this compound can be prepared by the method described in WO 2014 / 095675) + TX; methyl 3-[(4-chlorophenyl)methyl]-2-hydroxy-1-methyl-2-(1,2,4-triazol-1-ylmethyl)cyclopentanecarboxylate (this compound can be prepared by the method described in WO 2019 / 093522) + TX; methyl (2R)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propionate (this compound can be prepared by the method described in WO 2019 / 093522) + TX; 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[1-(2,6-difluorophenyl)cyclopropyl]pyrimidin-2-amine (this compound can be prepared by the method described in WO 2021 / 255093) + TX; aminopyrine (this compound can be prepared by the method described in WO 2014 / 006945) + TX; thiamethoxam (this compound can be prepared by the method described in WO 2011 / 138281) + TX; 1-[6-(difluoromethyl)-5-methyl-3-pyridyl]-4,4-difluoro-3,3-dimethyl-isoquinoline (this compound can be prepared by the method described in WO2017 / 016915) + TX; 1-[4-(difluoromethoxy)-2-methyl-phenyl]-2-(1,2,4-triazol-1-yl)-1-[1-(trifluoromethyl)cyclopropyl]ethanol (This compound can be prepared by the method described in WO 2021 / 249800) + TX; 1-[2-chloro-4-(difluoromethoxy)phenyl]-2-(1,2,4-triazol-1-yl)-1-[1-(trifluoromethyl)cyclopropyl]ethanol (This compound can be prepared by the method described in WO 2021 / 249800) + TX; 1-(5,6-dimethyl-3-pyridyl)-4,4-difluoro-3,3-dimethyl-isoquinoline (This compound can be prepared by the method described in WO 2017 / 016915) + TX; N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenylthiocarboxamide (this compound can be prepared by the method described in WO 2015 / 185485) + TX; 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide (this compound can be prepared by the method described in WO 2017 / 178245) + TX; fluopyram + TX;N-Methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide (this compound can be prepared by the method described in WO 2015 / 185485) + TX; (Z,2E)-5-[1-(2,4-dichlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide (this compound can be prepared by the method described in WO 2018 / 153707) + TX; (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide (this compound can be prepared by the method described in WO 2013 / 092224) + TX; (2E)-2-methoxyimino-2-[3-methyl-2-[[(E)-1-[4-(trifluoromethyl)-2-pyridyl]ethyleneamino]oxymethyl]phenyl]methyl acetate (this compound can be prepared by the method described in WO 2022 / 033906) + TX; (2E)-2-methoxyimino-N-methyl-2-[3-methyl-2-[[(E)-1-[4-(trifluoromethyl)-2-pyridyl]ethyleneamino]oxymethyl]phenyl]acetamide (this compound can be prepared by the method described in WO 2022 / 033906) + TX; (2E)-2-[2-[[(E)-[3-(4-fluorophenyl)-1-methyl-prop-2-ynyl]amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide (this compound can be prepared by WO 2022 / 033906) (Prepared by the method described in WO 2021 / 249928) + TX; (2E)-2-[2-[[(E)-[3-(4-fluorophenyl)-1-methyl-prop-2-ynyne]amino]oxymethyl]-3-methyl-phenyl]-2-methoxyimino-acetic acid methyl ester (This compound can be prepared by the method described in WO 2021 / 249928) + TX; 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazolium-4-carboxylonitrile (This compound can be prepared by the method described in WO 2016 / 156290) + TX; 3-[2-(1-chlorocyclopropyl)-3-(2-fluorophenyl)-2-hydroxy-propyl]imidazolium-4-carboxylonitrile (This compound can be prepared by the method described in WO 2016 / 156290) + TX; 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)prop-2-ol (this compound can be prepared by the method described in WO 2017 / 029179) + TX;2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)prop-2-ol (this compound can be prepared by the method described in WO 2017 / 029179) + TX; 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[1-(2-fluorophenyl)ethyl]pyrimidin-2-amine (this compound can be prepared by the method described in WO 2021 / 255093) + TX; 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[1-(3,5-difluorophenyl)ethyl]pyrimidin-2-amine (this compound can be prepared by the method described in WO 2021 / 255093) + TX; N-[1-(2-fluorophenyl)cyclopropyl]-5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]pyrimidin-2-amine (this compound can be prepared by the method described in WO 2021 / 255093) + TX; 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[1-(2,6-difluorophenyl)ethyl]pyrimidin-2-amine (this compound can be prepared by the method described in WO 2021 / 255093) + TX; 2-(difluoromethyl)-5-[2-[1-(2,6-difluorophenyl)cyclopropoxy]pyrimidin-5-yl]-1,3,4-oxadiazole (this compound can be prepared by the method described in WO 2021 / 255093) + TX; 5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-N-[1-(2-fluorophenyl)cyclopropyl]pyrimidin-2-amine (this compound can be prepared by the method described in WO 2021 / 255093) + TX; 5-[(4-bromo-2-methyl-phenyl)methyl]-3-[3-(3-chloro-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5,6-dihydro-4H-1,2,4-oxadiazine (this compound can be prepared by the method described in WO 2021 / 255070) + TX; 3-[3-(3-cyclopropyl-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5-[(2,4-dimethylphenyl)methyl]-5,6-dihydro-4H-1,2,4-oxadiazine (this compound can be prepared by WO 2021 / 255093) (Prepared by the method described in WO 2021 / 255070) + TX; N-(2,2,2-trifluoroethyl)-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]oxazol-4-carboxamide (this compound can be prepared by the method described in WO 2022 / 133114) + TX; 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenoxy]methyl]pyrazole-4-carboxylic acid ethyl ester (this compound can be prepared by the method described in WO 2022 / 133114) + TX;1-[[4-[(Z)-2-ethoxy-3,3,3-trifluoro-prop-1-enoxy]phenyl]methyl]pyrazole-4-carboxylic acid ethyl ester (this compound can be prepared by the methods described in WO 2020 / 056090 and WO 2021 / 183707) + TX; 1-[[4-[[2-(trifluoromethyl)-1,3-dioxolane-2-yl]methoxy]phenyl]methyl]pyrazole-4-carboxylic acid ethyl ester (this compound can be prepared by the methods described in WO 2020 / 056090 and WO 2021 / 183707) + TX; N-[[5-[4-(2,4-dimethylphenyl)triazol-2-yl]-2-methyl-phenyl]methyl]carbamate methyl ester (this compound can be prepared by the methods described in WO 2020 / 097012) + TX; Methyl N-[[5-[1-(2,6-difluoro-4-isopropyl-phenyl)pyrazol-3-yl]-2-methyl-phenyl]methyl]carbamate (this compound can be prepared by the method described in WO 2020 / 097012) + TX; Methyl N-[[5-[1-(4-cyclopropyl-2,6-difluoro-phenyl)pyrazol-3-yl]-2-methyl-phenyl]methyl]carbamate (this compound can be prepared by the method described in WO 2020 / 097012) + TX; Methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propionate (this compound can be prepared by the method described in WO 2019 / 093522) + TX; 4,4,5-trifluoro-3,3-dimethyl-1-(3-quinolinyl)isoquinoline + TX; 5-fluoro-3,3,4,4-tetramethyl-1-(3-quinolinyl)isoquinoline + TX; 2-methoxy-N-[methoxy-[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]acetamide (this compound can be prepared by the method described in WO 2020 / 256113) + TX; N-[methoxy-[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]-2-methyl-propionamide (this compound can be prepared by the method described in WO 2020 / 256113) + TX; N-[methoxy-[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]-2-thienyl]methyl]butyramide (this compound can be prepared by the method described in WO 2020 / 256113) + TX; 2-(difluoromethyl)-N-[(3R)-3-ethyl-1,1-dimethyl-indan-4-yl]pyridine-3-carboxamide (this compound can be prepared by the method described in WO 2014 / 095675) + TX;2-(difluoromethyl)-N-(3-ethyl-1,1-dimethyl-indane-4-yl)pyridine-3-carboxamide (this compound can be prepared by the method described in WO 2014 / 095675) + TX; 2-(difluoromethyl)-N-(1,1,3-trimethylindane-4-yl)pyridine-3-carboxamide + TX; (5R)-3-[3-(3-chloro-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5-[(2-chloro-4-methyl-phenyl)methyl]-5,6-dihydro-4H-1,2,4-oxadiazine (this compound can be prepared by the methods described in WO 2020 / 127780 and WO 2021 / 255070) + TX; (5S)-3-[3-(3-chloro-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5-[(2-chloro-4-methyl-phenyl)methyl]-5,6-dihydro-4H-1,2,4-oxadiazine (This compound can be prepared by the methods described in WO 2020 / 127780 and WO 2021 / 255070) + TX; 3-[3-(3-chloro-2-fluoro-phenoxy)-6-methyl-pyridazin-4-yl]-5-[(2-chloro-4-methyl-phenyl)methyl]-5,6-dihydro-4H-1,2,4-oxadiazine (This compound can be prepared by the methods described in WO 2020 / 127780 and WO 2021 / 255070) + TX; (Z)-3-methoxy-2-(2-methyl-5-phenyl-phenoxy)prop-2-enoic acid methyl ester (this compound can be prepared by the method described in JP 2023078251) + TX; 2-[(2,6-difluoro-4-pyridinyl)-(2-methylpropionyl)amino]-N-(2,2-dimethylcyclobutyl)-5-methyl-thiazol-4-carboxamide + TX; or (; R )or( S Enantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO 2019105933 A1, WO2020109511 A1, WO 2021244952 A1); 2-[(2,6-difluoro-4-pyridinyl)-(tetrahydropyran-4-carbonyl)amino]-N-(2,2-dimethylcyclobutyl)-5-methyl-thiazolyl-4-carboxamide + TX; or ( R )or( SEnantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO 2019105933 A1, WO2020109511 A1, WO 2021244952 A1); 2-[cyano-(2,6-difluoro-4-pyridinyl)amino]-5-methyl-N-spiro[3,4]octane-3-yl-thiazolyl-4-carboxamide + TX; or ( R )or( S Enantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO 2019105933 A1, WO 2020109509 A1); 2-[cyano-(2,6-difluoro-4-pyridinyl)amino]-N-(2,2-dimethylcyclobutyl)-5-methyl-thiazolyl-4-carboxamide + TX; or ( R )or( S Enantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO2017207362 A1, WO 2019105933 A1, WO 2020109509 A1); 2-[(2,6-difluoro-4-pyridinyl)-(2-methoxyacetyl)amino]-N-(2,2-dimethylcyclobutyl)-5-methyl-thiazolyl-4-carboxamide + TX; or ( R )or( S Enantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO2019105933 A1, WO 2020109511 A1, WO 2021244952 A1); 2-[acetyl-(2,6-difluoro-4-pyridyl)amino]-5-methyl-N-spiro[3,4]octane-3-yl-thiazolyl-4-carboxamide + TX; or ( R )or( SEnantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO 2019105933 A1, WO 2020109511 A1, WO 2021244952 A1); N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropaneformamide (this compound can be prepared by the methods described in WO 2017 / 055473) + TX; (Z)-2-(5-cyclopentyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoic acid methyl ester (this compound can be prepared by the methods described in WO 2020 / 193387) + TX; (Z)-2-(5-cyclohexyl-2-methyl-phenoxy)-3-methoxy-prop-2-enoic acid methyl ester (this compound can be prepared by the method described in WO 2020 / 193387) + TX; N-[(1R)-1-benzyl-1,3-dimethylbutyl]-8-fluoroquinoline-3-carboxamide (this compound can be prepared by the method described in WO 2017 / 153380) + TX; N-[(1S)-1-benzyl-1,3-dimethylbutyl]-8-fluoroquinoline-3-carboxamide (this compound can be prepared by the method described in WO 2017 / 153380) + TX; 2-[(2,6-difluoro-4-pyridinyl)-(oxetane-3-carbonyl)amino]-N-(2,2-dimethylcyclobutyl)-5-methyl-thiazol-4-carboxamide+ TX; or ( R )or( S Enantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO 2019105933 A1, WO 2020109511 A1, WO 2021244952 A1); 2-[acetyl-(2,6-difluoro-4-pyridyl)amino]-N-(2,2-dimethylcyclobutyl)-5-methyl-thiazolyl-4-carboxamide + TX; or ( R )or( S Enantiomers or mixtures thereof + TX (this compound can be prepared by the methods described in WO 2017207362 A1, WO 2019105933 A1, WO2020109511 A1, WO 2021244952 A1); N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propionamide + TX; or ( R )or( SEnantiomers or mixtures thereof + TX (This compound can be prepared by the method described in WO 2017 / 055473). Reference in parentheses after the active ingredient (e.g.) [3878-19-1] ) refers to the Chemical Abstracts Service Registry number. The mixtures described above are known. In cases where the active ingredient is included in "The Pesticide Manual" [The Pesticide Manual - A World Compendium; 13th edition; edited by CDS TomLin; The British Crop Protection Council], they are described therein by the entry number given in parentheses above for the specific compound; for example, the compound "Abamedin" is described by entry number (1). In cases where "[CCN]" is added above to a specific compound, the compound is included in "Compendium of Pesticide Common Names," which is available on the Internet [A. Wood; Compendium of Pesticide Common Names [Copyright © 1995-2004]; for example, the compound “acetoprole” is described at the Internet address http: / / www.alanwood.net / pesticides / acetoprole.html.

[0318] Most of the aforementioned active ingredients are referred to above by their so-called “generic names,” with the corresponding “ISO generic name” or another “generic name” used in individual cases. If the name is not a “generic name,” the type of name used is replaced by the name given in parentheses for the specific compound; in this case, the IUPAC name, IUPAC / Chemical Abstracts name, “chemical name,” “common name,” “compound name,” or “development code” is used, or if neither of those names nor a “generic name” is used, an “alias” is used. “CAS Registry Number” refers to the Chemical Abstracts Registry Number.

[0319] The active ingredient mixture of compounds selected from the group consisting of compounds having formula (I), (II), (III), or (III-A), or compounds selected from those listed in Tables C-1 to C-60 or Table P (hereinafter), is preferably in a mixing ratio from 100:1 to 1:100, especially from 50:1 to 1:50, more especially from 20:1 to 1:20, even more especially from 10:1 to 1:10, and still more especially from 5:1 to 1:5. These mixing ratios are by weight.

[0320] The mixture described above can be used in methods for controlling pests, excluding methods of treating humans or animals by surgical or therapeutic procedures and diagnostic methods performed on humans or animals, such as applying a composition containing the mixture described above to pests or their environment.

[0321] A mixture comprising a compound selected from compounds having formula (I), (II), (III), or (III-A), or compounds selected from those listed in Tables C-1 to C-60 or Table P (hereinafter), and one or more active ingredients as described above, may be applied, for example, as a single "ready-to-use with water" formulation, as a combined spray mixture consisting of individual formulations of a single active ingredient component, such as a "bucket mix," and when applied sequentially, i.e., one after another over a reasonable period of time (e.g., hours or days), using a single active ingredient in combination. The order in which the compound selected from compounds having formula (I), (II), (III), or (III-A), or compounds selected from those listed in Tables C-1 to C-60 or Table P (hereinafter), and one or more active ingredients as described above are applied is not important for carrying out the invention.

[0322] The compositions according to the invention may also contain additional solid or liquid adjuvants, such as stabilizers, for example un-epoxidized or epoxidized vegetable oils (e.g., epoxidized coconut oil, rapeseed oil, or soybean oil), defoamers (e.g., silicone oil), preservatives, viscosity modifiers, binders and / or thickeners, fertilizers, or other active ingredients for achieving specific effects, such as bactericides, fungicides, nematicides, plant activators, molluscicides, or herbicides.

[0323] The compositions according to the invention are prepared in a manner known per se, in the absence of adjuvants, for example by grinding, sieving, and / or compressing solid active ingredients; and in the presence of at least one adjuvant, for example by tightly mixing the active ingredient with one or more adjuvants and / or grinding the active ingredient together with one or more adjuvants. These methods for preparing the compositions and the use of the compound (I) for preparing these compositions are also the subject of this invention.

[0324] Another aspect of the invention relates to the use of a fungicide or insecticide mixture comprising a compound of formula (I) or preferably various compounds as defined herein, a composition comprising at least one compound of formula (I) or at least one preferred compound as defined herein, or a mixture comprising at least one compound of formula (I) or at least one preferred compound as defined herein (mixed with other fungicides or insecticides as described above) for controlling or preventing infection of plants (e.g., useful plants (such as crop plants)), their reproductive material (e.g., seeds), harvested crops (e.g., harvested food crops), or inanimate materials by insects or plant pathogenic microorganisms (preferably fungal organisms).

[0325] Another aspect of the invention relates to a method for controlling or preventing the infection of plants (e.g., useful plants, such as crop plants), their propagation material (e.g., seeds), harvested crops (e.g., harvested food crops), or inanimate materials by plant pathogenic microorganisms or putrefactive microorganisms or organisms potentially harmful to humans (especially fungal organisms), the method comprising applying as an active ingredient a compound having formula (I) according to the invention or preferably various compounds as defined herein to these plants, parts of these plants or their sites, their propagation material, or any part of these inanimate materials.

[0326] Control or prevention means reducing the infestation of insect or plant pathogenic microorganisms or putrefactive microorganisms or potentially harmful organisms (especially fungal organisms) to such a proven improved level.

[0327] A preferred method for controlling or preventing crop infection by plant pathogenic microorganisms (especially fungal organisms) or insects is foliar application, which includes applying a compound of formula (I) according to the invention, or an agricultural chemical composition containing at least one compound of formula (I). The frequency and ratio of application will depend on the risk of infection by the corresponding pathogen or insect. However, the compound of formula (I) according to the invention can also penetrate the plant through the soil via roots (systemic absorption) by soaking the plant in a liquid formulation or by applying the compound in solid form, such as in granules, to the soil (soil application). In rice crops, such granules can be applied to irrigated paddy fields. The compound of formula (I) can also be applied to seeds (coating) by soaking the seeds or tubers in a liquid formulation of a fungicide or by coating them with a solid formulation.

[0328] Formulations (e.g., compositions containing compounds of formula (I) according to the invention, and (if desired) solid or liquid adjuvants or monomers for encapsulating compounds of formula (I)) can be prepared in a known manner, typically by closely mixing and / or grinding the compound with an adjuvant (e.g., a solvent, a solid carrier, and optionally a surfactant compound).

[0329] Favorable application rates are typically from 5 g to 2 kg of active ingredient (ai) per hectare (ha), preferably from 10 g to 1 kg ai / ha, and most preferably from 20 g to 600 g ai / ha. When used as a seed soaking agent, the appropriate dosage is from 10 mg to 1 g of active substance per kg of seeds.

[0330] As used herein, the term "g ai / ha" refers to the application ratio given in grams (g) of active ingredient (ai) per unit surface area (ha). A unit hectare (symbol ha) is equal to a hectare with a side length of 100 m (1 hm²). 2 The hectare is a metric unit of area, representing a square area of ​​10,000 square meters or 10,000 square meters. The hectare is a commonly used unit of area in the metric system.

[0331] When the combination of the present invention is used to treat seeds, an application rate of 0.001 to 50 g of the compound of formula (I) per kg of seeds, preferably from 0.01 to 10 g per kg of seeds, is generally sufficient.

[0332] Appropriately, compositions comprising compounds having formula (I) according to the invention may be applied preventively (meaning before the development of the disease) or therapeutically (meaning after the development of the disease).

[0333] The compositions of the present invention can be used in any conventional form, such as in the form of double-packaged powders for dry seed treatment (DS), emulsions for seed treatment (ES), flowable concentrates for seed treatment (FS), solutions for seed treatment (LS), water-dispersible powders for seed treatment (WS), capsule suspensions for seed treatment (CF), gels for seed treatment (GF), emulsion concentrates (EC), suspension concentrates (SC), suspension emulsions (SE), capsule suspensions (CS), water-dispersible particles (WG), emulsifiable particles (EG), water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), dispersible oil suspensions (OD), oil suspensions (OF), oil-soluble liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical grade (TK), dispersible concentrates (DC), wettable powders (WP), or any technically feasible formulations in combination with agriculturally acceptable adjuvants.

[0334] Such compositions can be produced in conventional ways, for example by mixing the active ingredient with appropriate formulation inert agents (diluents, solvents, fillers, and optionally other formulation components such as surfactants, biocides, antifreeze agents, adhesives, thickeners, and compounds that provide auxiliary effects). Conventional sustained-release formulations designed for long-term sustained efficacy can also be used. In particular, formulations intended for application in spray form, such as water-dispersible concentrates (e.g., EC, SC, DC, OD, SE, EW, EO, etc.), wettable powders, and granules, may contain surfactants such as wetting agents and dispersants, and other compounds that provide auxiliary effects, such as condensation products of formaldehyde with naphthalene sulfonates, alkylaryl sulfonates, lignin sulfonates, fatty alkyl sulfates, and ethoxylated alkylphenols and ethoxylated fatty alcohols.

[0335] The seed dressing formulation is applied to seeds in a manner known per se using the combination and diluent of the present invention in a suitable seed dressing formulation form (e.g., an aqueous suspension or dry powder form with good adhesion to seeds). Such seed dressing formulations are known in the art. The seed dressing formulation may contain a single active ingredient or a combination of active ingredients in encapsulated form, for example, as a sustained-release capsule or microcapsule.

[0336] Typically, these formulations contain from 0.01% to 90% by weight of an active agent, from 0% to 20% of an agriculturally acceptable surfactant, and from 10% to 99.99% of a solid or liquid formulation inert agent, as well as one or more adjuvants, wherein the active agent is optionally composed of at least a compound of formula (I) according to the invention, together with other active agents (particularly microbicides or preservatives, etc.). Concentrated forms of the composition typically contain between about 2% and 80% by weight of the active agent, preferably between about 5% and 70%. The formulation may be administered in an application form containing, for example, from 0.01% to 20% by weight of the active agent, preferably from 0.01% to 5% by weight. However, commercially available products will preferably be formulated as concentrates, and end users will typically use diluted formulations.

[0337] However, it is preferable to formulate commercial products as concentrates, while end users will typically use diluted formulations.

[0338] Application rates vary widely and depend on soil properties, application method, crop, pests to be controlled, primary climatic conditions, and other factors governed by application method, application time, and target crop. Generally, compounds can be applied at rates ranging from 1 l / ha to 2000 l / ha, particularly from 10 l / ha to 1000 l / ha.

[0339] Preferred formulations may have the following composition (by weight%):

[0340] Emulsifiable concentrate :

[0341] Active ingredient: 1% to 95%, preferably 60% to 90%

[0342] Surfactant: 1% to 30%, preferably 5% to 20%

[0343] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0344] Dust powder :

[0345] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%

[0346] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%.

[0347] Suspension concentrate:

[0348] Active ingredient: 5% to 75%, preferably 10% to 50%

[0349] Water: 94% to 24%, preferably 88% to 30%

[0350] Surfactant: 1% to 40%, preferably 2% to 30%

[0351] wettable powder :

[0352] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0353] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0354] Solid carrier: 5% to 95%, preferably 15% to 90%

[0355] Granules:

[0356] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%

[0357] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0358] The disclosures in this application make it possible to obtain every combination of the embodiments disclosed herein.

[0359] The compounds according to Tables C-1 to C-60 below can be prepared according to the method described above. The following examples are intended to illustrate the invention and demonstrate preferred compounds having formula (I). In any of Tables C-1 to C-60 below, the presence of one or more possible asymmetric carbon atoms in the compounds having formula (I) according to the invention means that these compounds can exist in chiral isomers, i.e., enantiomers or diastereomers.

[0360] The disclosures in this application make it possible to obtain every combination of the embodiments disclosed herein.

[0361] The compounds according to Tables C-1 to C-60 below can be prepared according to the method described above. Subsequent examples are intended to illustrate the invention and demonstrate preferred compounds having formula (I).

[0362] Table A This table discloses the 20 substituent definitions G of formula (I).

[0363] (I), where G has the formula

[0364]

[0365] As defined below:

[0366]

[0367] Table B This table discloses the 20 substituent definitions Q of formula (I).

[0368] (I)

[0369]

[0370] Tables C-1 to C-60 disclose specific compounds of the present invention having formula (I).

[0371] (I), where the Q and G substituents are as defined in Tables A and B.

[0372] Table C-1: This table provides 20 compounds of formula (I) from C-1.01 to C-1.20, wherein R 2 R 4 R 5 R 6 H is H, Q is Q-1 as defined in Table B, and G is as defined in Table A. For example, compound C-1.01 has the following structure:

[0373] Compound C-1.01

[0374] Table C-2: This table provides 20 compounds of formula (I) from C-2.01 to C-2.20, wherein R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-1 as defined in Table B, and G is as defined in Table A. For example, compound C-2.10 has the following structure:

[0375] Compound C-2.10

[0376] Table C-3: This table provides 20 compounds of formula (I) from C-3.01 to C-3.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-1 as defined in Table B, and G is as defined in Table A. For example, compound C-3.18 has the following structure:

[0377] Compound C-3.18

[0378] Table C-4: This table provides 20 compounds of formula (I) from C-4.01 to C-4.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-2 as defined in Table B, and G is as defined in Table A.

[0379] Table C-5: This table provides 20 compounds of formula (I) from C-5.01 to C-5.20, wherein R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-2 as defined in Table B, and G is as defined in Table A.

[0380] Table C-6: This table provides 20 compounds of formula (I) from C-6.01 to C-6.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-2 as defined in Table B, and G is as defined in Table A.

[0381] Table C-7: This table provides 20 compounds of formula (I) from C-7.01 to C-7.20, wherein R 2 R 4 R 5 R 6 H is H, Q is Q-3 as defined in Table B, and G is as defined in Table A.

[0382] Table C-8: This table provides 20 compounds of formula (I) from C-8.01 to C-8.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-3 as defined in Table B, and G is as defined in Table A.

[0383] Table C-9: This table provides 20 compounds of formula (I) from C-9.01 to C-9.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-3 as defined in Table B, and G is as defined in Table A.

[0384] Table C-10: This table provides 20 compounds of formula (I) from C-10.01 to C-10.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-4 as defined in Table B, and G is as defined in Table A.

[0385] Table C-11: This table provides 20 compounds of formula (I) from C-11.01 to C-11.20, wherein R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-4 as defined in Table B, and G is as defined in Table A.

[0386] Table C-12: This table provides 20 compounds of formula (I) from C-12.01 to C-12.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-4 as defined in Table B, and G is as defined in Table A.

[0387] Table C-13: This table provides 20 compounds of formula (I) from C-13.01 to C-13.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-5 as defined in Table B, and G is as defined in Table A.

[0388] Table C-14: This table provides 20 compounds of formula (I) from C-14.01 to C-14.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-5 as defined in Table B, and G is as defined in Table A.

[0389] Table C-15: This table provides 20 compounds of formula (I) from C-15.01 to C-15.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-5 as defined in Table B, and G is as defined in Table A. For example, compound C-15.04 has the following structure:

[0390] Compound C-15.04

[0391] Table C-16: This table provides 20 compounds of formula (I) from C-16.01 to C-16.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-6 as defined in Table B, and G is as defined in Table A.

[0392] Table C-17: This table provides 20 compounds of formula (I) from C-17.01 to C-17.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-6 as defined in Table B, and G is as defined in Table A.

[0393] Table C-18: This table provides 20 compounds of formula (I) from C-18.01 to C-18.20, where R 5R 6 It is H, R 2 and R 4 It is CH3, Q is Q-6 as defined in Table B, and G is as defined in Table A.

[0394] Table C-19: This table provides 20 compounds of formula (I) from C-19.01 to C-19.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-7 as defined in Table B, and G is as defined in Table A.

[0395] Table C-20: This table provides 20 compounds of formula (I) from C-20.01 to C-20.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-7 as defined in Table B, and G is as defined in Table A.

[0396] Table C-21: This table provides 20 compounds of formula (I) from C-21.01 to C-21.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-7 as defined in Table B, and G is as defined in Table A.

[0397] Table C-22: This table provides 20 compounds of formula (I) from C-22.01 to C-22.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-8 as defined in Table B, and G is as defined in Table A.

[0398] Table C-23: This table provides 20 compounds of formula (I) from C-23.01 to C-23.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-8 as defined in Table B, and G is as defined in Table A.

[0399] Table C-24: This table provides 20 compounds of formula (I) from C-24.01 to C-24.20, where R5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-8 as defined in Table B, and G is as defined in Table A.

[0400] Table C-25: This table provides 20 compounds of formula (I) from C-25.01 to C-25.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-9 as defined in Table B, and G is as defined in Table A.

[0401] Table C-26: This table provides 20 compounds of formula (I) from C-26.01 to C-26.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-9 as defined in Table B, and G is as defined in Table A.

[0402] Table C-27: This table provides 20 compounds of formula (I) from C-27.01 to C-27.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-9 as defined in Table B, and G is as defined in Table A.

[0403] Table C-28: This table provides 20 compounds of formula (I) from C-28.01 to C-28.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-10 as defined in Table B, and G is as defined in Table A.

[0404] Table C-29: This table provides 20 compounds of formula (I) from C-29.01 to C-29.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-10 as defined in Table B, and G is as defined in Table A.

[0405] Table C-30:This table provides 20 compounds of formula (I) from C-30.01 to C-30.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-10 as defined in Table B, and G is as defined in Table A.

[0406] Table C-31: This table provides 20 compounds of formula (I) from C-31.01 to C-31.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-11 as defined in Table B, and G is as defined in Table A.

[0407] Table C-32: This table provides 20 compounds of formula (I) from C-32.01 to C-32.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-11 as defined in Table B, and G is as defined in Table A.

[0408] Table C-33: This table provides 20 compounds of formula (I) from C-33.01 to C-33.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-11 as defined in Table B, and G is as defined in Table A.

[0409] Table C-34: This table provides 20 compounds of formula (I) from C-34.01 to C-34.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-12 as defined in Table B, and G is as defined in Table A.

[0410] Table C-35: This table provides 20 compounds of formula (I) from C-35.01 to C-35.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-12 as defined in Table B, and G is as defined in Table A.

[0411] Table C-36: This table provides 20 compounds of formula (I) from C-36.01 to C-36.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-12 as defined in Table B, and G is as defined in Table A.

[0412] Table C-37: This table provides 20 compounds of formula (I) from C-37.01 to C-37.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-13 as defined in Table B, and G is as defined in Table A.

[0413] Table C-38: This table provides 20 compounds of formula (I) from C-38.01 to C-38.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-13 as defined in Table B, and G is as defined in Table A.

[0414] Table C-39: This table provides 20 compounds of formula (I) from C-39.01 to C-39.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-13 as defined in Table B, and G is as defined in Table A.

[0415] Table C-40: This table provides 20 compounds of formula (I) from C-40.01 to C-40.20, wherein R 2 R 4 R 5 R 6 H is H, Q is Q-14 as defined in Table B, and G is as defined in Table A.

[0416] Table C-41: This table provides 20 compounds of formula (I) from C-41.01 to C-41.20, where R 2 R 5 R 6 It is H, R 4It is CH3, Q is Q-14 as defined in Table B, and G is as defined in Table A.

[0417] Table C-42: This table provides 20 compounds of formula (I) from C-42.01 to C-42.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-14 as defined in Table B, and G is as defined in Table A.

[0418] Table C-43: This table provides 20 compounds of formula (I) from C-43.01 to C-43.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-15 as defined in Table B, and G is as defined in Table A.

[0419] Table C-44: This table provides 20 compounds of formula (I) from C-44.01 to C-44.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-15 as defined in Table B, and G is as defined in Table A.

[0420] Table C-45: This table provides 20 compounds of formula (I) from C-45.01 to C-45.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-15 as defined in Table B, and G is as defined in Table A.

[0421] Table C-46: This table provides 20 compounds of formula (I) from C-46.01 to C-46.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-16 as defined in Table B, and G is as defined in Table A.

[0422] Table C-47: This table provides 20 compounds of formula (I) from C-47.01 to C-47.20, where R 2 R 5 R 6It is H, R 4 It is CH3, Q is Q-16 as defined in Table B, and G is as defined in Table A.

[0423] Table C-48: This table provides 20 compounds of formula (I) from C-48.01 to C-48.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-16 as defined in Table B, and G is as defined in Table A.

[0424] Table C-49: This table provides 20 compounds of formula (I) from C-49.01 to C-49.20, where R 2 R 4 R 5 R 6 H is Q, Q is Q-i7 as defined in Table B, and G is as defined in Table A.

[0425] Table C-50: This table provides 20 compounds of formula (I) from C-50.01 to C-50.20, wherein R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-17 as defined in Table B, and G is as defined in Table A.

[0426] Table C-51: This table provides 20 compounds of formula (I) from C-51.01 to C-51.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-17 as defined in Table B, and G is as defined in Table A.

[0427] Table C-52: This table provides 20 compounds of formula (I) from C-52.01 to C-52.20, wherein R 2 R 4 R 5 R 6 H is H, Q is Q-18 as defined in Table B, and G is as defined in Table A.

[0428] Table C-53: This table provides 20 compounds of formula (I) from C-53.01 to C-53.20, where R 2 R 5R 6 It is H, R 4 It is CH3, Q is Q-18 as defined in Table B, and G is as defined in Table A.

[0429] Table C-54: This table provides 20 compounds of formula (I) from C-54.01 to C-54.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-18 as defined in Table B, and G is as defined in Table A.

[0430] Table C-55: This table provides 20 compounds of formula (I) from C-55.01 to C-55.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-19 as defined in Table B, and G is as defined in Table A.

[0431] Table C-56: This table provides 20 compounds of formula (I) from C-56.01 to C-56.20, where R 2 R 5 R 6 It is H, R 4 It is CH3, Q is Q-19 as defined in Table B, and G is as defined in Table A.

[0432] Table C-57: This table provides 20 compounds of formula (I) from C-57.01 to C-57.20, where R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-19 as defined in Table B, and G is as defined in Table A.

[0433] Table C-58: This table provides 20 compounds of formula (I) from C-58.01 to C-58.20, where R 2 R 4 R 5 R 6 H is H, Q is Q-20 as defined in Table B, and G is as defined in Table A.

[0434] Table C-59: This table provides 20 compounds of formula (I) from C-59.01 to C-59.20, where R 2R 5 R 6 It is H, R 4 It is CH3, Q is Q-20 as defined in Table B, and G is as defined in Table A. For example, compound C-59.13 has the following structure:

[0435] Compound C-59.13

[0436] Table C-60: This table provides 20 compounds of formula (I) from C-60.01 to C-60.20, wherein R 5 R 6 It is H, R 2 and R 4 It is CH3, Q is Q-20 as defined in Table B, and G is as defined in Table A.

[0437] Example

[0438] The following examples are used to illustrate the invention and are not intended to limit the invention in any way.

[0439] The compounds of the present invention differ from known compounds in that they have greater efficacy at lower application rates, which can be confirmed by those skilled in the art using the experimental procedures outlined in the examples, with lower application rates (if necessary), such as 60 ppm, 20 ppm, or 2 ppm.

[0440] Compounds having formula (I) can have many benefits. especially This includes favorable levels of bioactivity for protecting plants against fungal diseases or superior properties for use as active ingredients in agrochemicals (e.g., higher bioactivity, favorable activity spectrum, increased safety (including improved crop tolerance), improved physicochemical properties, or increased biodegradability).

[0441] Examples of preparations

[0442]

[0443] The combination is thoroughly mixed with these additives and the mixture is thoroughly ground in a suitable grinder to obtain a wettable powder that can be diluted with water to obtain a suspension of the desired concentration.

[0444]

[0445] The combination is thoroughly mixed with these adjuvants and the mixture is thoroughly ground in a suitable grinder to obtain a powder that can be used directly for seed treatment.

[0446] Emulsifiable concentrate

[0447]

[0448] Emulsions with any required dilution that can be used in plant protection can be obtained from such concentrates by diluting them with water.

[0449]

[0450] A ready-to-use dust powder is obtained by mixing the mixture with a carrier and grinding the mixture in a suitable grinder. This type... dust Powder can also be used for dry seed dressing.

[0451] Extruder granules

[0452]

[0453] The mixture is combined with these additives and ground, and then the mixture is moistened with water. The mixture is extruded and then dried in an air stream.

[0454] Coated granules

[0455]

[0456] The finely ground mixture is then uniformly applied in a mixer to kaolin moistened with polyethylene glycol. This process yields dust-free coated granules.

[0457] suspension concentrate

[0458]

[0459] The finely ground mixture is then tightly mixed with these adjuvants to obtain a suspension concentrate, from which a suspension concentrate can be diluted with water to obtain a suspension of any desired dilution. Using such a dilution, living plants along with their propagation material can be treated and protected against microbial infection by spraying, watering, or immersion.

[0460] Flowable concentrate for seed treatment

[0461]

[0462] The finely ground mixture is tightly blended with adjuvants to obtain a flowable concentrate, from which solutions of any desired dilution can be obtained by dilution with water. These solutions can be used directly for seed treatment. Using such solutions, living plants and plant propagation material can be treated and protected from microbial contamination by spraying, watering, or immersion.

[0463] Sustained-release capsule suspension

[0464] 28 parts of the mixture were combined with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenyl isocyanate mixture (8:1). This mixture was emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of an antifoaming agent, and 51.6 parts of water until the desired particle size was achieved. 2.8 parts of a 1,6-hexanediamine mixture in 5.3 parts of water were added to this emulsion. The mixture was stirred until polymerization was complete. The resulting capsule suspension was stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersant. This capsule suspension formulation contained 28% of the active ingredient. The diameter of the medium capsules was 8-15 micrometers. The resulting formulation was applied to seeds as an aqueous suspension suitable for this application.

[0465] Formulation types include emulsion concentrates (EC), suspension concentrates (SC), suspension emulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), emulsions, water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersions (OD), oil suspensions (OF), oil-soluble liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical grade (TK), dispersible concentrates (DC), wettable powders (WP), soluble granules (SG), or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

[0466] abbreviation

[0467]

[0468] Preparation Examples

[0469] The compounds having formula (I) according to the present invention can be prepared using the synthesis techniques described above and below.

[0470] Recorded on a Bruker 400MHz spectrometer 1 H NMR and 19 F NMR measurements, chemical shift relative to TMS ( 1 H) and CFCl3 ( 19 F) Standards are given in ppm. Spectra were measured in deuterated solvents as specified. These compounds were characterized using any of the following LCMS methods. The characteristic LCMS values ​​obtained for each compound are retention time (“Rt”, recorded in minutes) and the measured molecular ion [M+H]. +Or [MH] - .

[0471] Throughout this specification, temperatures are given in degrees Celsius (°C) and "mp" indicates melting point. Free radicals represent methyl groups.

[0472] LC / MS, LC-MS, or LCMS refers to liquid chromatography-mass spectrometry, and the apparatus and method are described below.

[0473] Method A (LCMS): Spectra were recorded on an ACQUITY mass spectrometer (SQD or SQDII single quadrupole mass spectrometer) from Waters Corporation, equipped with an electro-ejector source (polarity: positive or negative ion, capillary: 3.0 kV, cone: 30 V, extractor: 3.00 V, source temperature: 150°C, desolvation temperature: 400°C, cone gas flow rate: 60 L / hr, desolvation gas flow rate: 700 L / hr, mass range: 140 to 800 Da) and an ACQUITY UPLC from Waters Corporation, which features a solvent degassing unit, a binary pump, a heated column chamber, and a diode array detector. Column: Waters UPLC HSS T3, 1.8 µm, 30 × 2.1 mm, temperature: 60°C, DAD wavelength range (nm): 210 to 400, solvent gradient: A = water / methanol 9:1 + 0.1% formic acid, B = acetonitrile + 0.1% formic acid, gradient: 0-100% B, over 3.0 min; flow rate (ml / min): 0.75.

[0474] Method B (LCMS):Spectra were recorded on a Waters mass spectrometer (Acquity QDa mass spectrometer), equipped with an electro-jet source (polarity: positive and negative polarity switching), capillary: 0.8 kV, cone range: 25 V, extractor: V (Qda detector has no extractor voltage), source temperature: 120°C, desolvation temperature: 600°C, cone gas flow rate: 50 L / h, desolvation gas flow rate: 1000 L / h, mass range: 110 to 850 Da) and a Waters Acquity UPLC: quaternary solvent manager, heated column chamber, and diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 µm, 30 × 2.1 mm, Temperature: 40°C, DAD wavelength range (nm): 200 to 400, Solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; Gradient: 0 min 10% B; 0.0-0.2 min 10%-50% B; 0.2-0.6 min 50%-100% B; 0.6-1.3 min 100% B; 1.3-1.4 min 100%-10% B; 1.4-1.6 min 10% B; Flow rate (mL / min): 0.6.

[0475] Method C (LCMS): Spectra were recorded on an Agilent Technologies MSD-IQ mass spectrometer equipped with an electro-jet source (polarity: positive or negative ion, MS2 scan, capillary: 3.5 kV, fragmenter: 110 V, desolvation temperature: 325°C, gas flow rate: 13 L / min, nebulizer gas: 55 psi, mass range: 110 to 850 Da) and an Agilent 1290 Series HPLC: quaternary pump, heated column chamber, and diode array detector. Column: AGILENT POROSHELL 120 EC-C18, 1.9 µm, 50 × 2.1 mm; Temperature: 40°C; DAD wavelength range (nm): 190 to 400; Solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.1% HCOOH; Gradient: 0–0.5 min 10% B, 90% A; 1.2–1.5 min 95% B, 0.5% A; 1.8–2.5 min 10% B, 90% A; Flow rate (mL / min): 0.8

[0476] Method D (LCMS):Spectra were recorded on a Waters mass spectrometer (SQD2 or QDA single quadrupole mass spectrometer) equipped with an electro-jet source (polarity: positive and negative polarity switching, capillary: 0.8–3.00 kV, cone range: 25, source temperature: 120°C–150°C, desolvation temperature: 500°C–600°C, cone gas flow rate: 50 L / h, desolvation gas flow rate: 1000 L / h, mass range: 110–850 Da) and a Waters Acquity UPLC: quaternary solvent manager, heated column chamber, and diode array detector. Column: Acquity UPLC HSS T3 C18, 1.8 µm, 30 × 2.1 mm, Temperature: 40°C, DAD wavelength range (nm): 200 to 400, Solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; Gradient: 0 min 10% B; 0.0-0.2 min 10%-50% B; 0.2-0.6 min 50%-100% B; 0.6-1.3 min 100% B; 1.3-1.4 min 100%-10% B; 1.4-1.6 min 10% B; Flow rate (mL / min): 0.6.

[0477] Method E (LCMS): Spectra were recorded on a mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) from Waters Corporation, equipped with an electro-jet source (polarity: positive and negative ions), capillary: 3.00 kV, cone range: 30 V, extractor: 2.00 V, source temperature: 150°C, desolvation temperature: 350°C, cone gas flow rate: 50 l / h, desolvation gas flow rate: 650 l / h, mass range: 100 to 900 Da) and an Acquity UPLC from Waters Corporation: binary pump, heated column chamber, diode array detector, and ELSD detector. Column: Waters UPLC HSS T3, 1.8 µm, 30 × 2.1 mm; Temperature: 60°C; DAD wavelength range (nm): 210 to 500; Solvent gradient: A = Water + 5% MeOH + 0.05% HCOOH, B = Acetonitrile + 0.05% HCOOH; Gradient: 10%–100% B over 1.2 min; Flow rate (ml / min): 0.85

[0478] Preparation Examples

[0479] Example P1: N -[2-(4-Cyclopropylthiazolin-2-yl)-2-(1-Methylpyrazole-4-yl)propyl]-1-(2,4-Difluoro Preparation of phenyl)triazole-4-carboxamide (compound P-2, Table P)

[0480] Compound P-2, Table P

[0481] Step 1: Preparation of 2-(1-methylpyrazol-4-yl)propionitrile

[0482]

[0483] Under argon atmosphere, a sample of 2-(1-methyl-1h-pyrazol-4-yl)acetonitrile (CAS: 754159-15-4, 10.00 g, 78.42 mmol) was dissolved in THF (314 mL), and the pale yellow solution was cooled to -78°C. To this solution, n-butyllithium (31 mL, 78.42 mmol) was added dropwise, and the resulting pale brown suspension was stirred at this temperature for 25 minutes. After this time, iodomethane (11.24 g, 4.93 mL, 78.42 mmol) was added dropwise. The resulting brown solution was stirred at -78°C for 5 minutes, then heated to room temperature and stirred under argon atmosphere for 30 minutes. The reaction mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed once with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum to give 2-(1-methylpyrazol-4-yl)propionitrile as a light brown liquid.

[0484] LC / MS (Method E); RT = 0.43 min, 136 [M+H], 1 H NMR (400 MHz, CDCl3) δ ppm1.64 (d, J =6.90 Hz, 3 H) 3.86 - 3.93 (m, 4 H) 7.40 (s, 1 H) 7.46 (s, 1 H).

[0485] Step 2: Preparation of 2-(4-cyclopropylthiazolyl)-2-(1-methylpyrazol-4-yl)propionitrile

[0486]

[0487] Method A:

[0488] Step 2Aa: Preparation of (2-cyclopropyl-2-oxo-ethyl)thiocyanate

[0489]

[0490] A solution of 2-bromo-1-cyclopropyl-ethyl ketone (1.7 g, 10 mmol) in ethanol (10 mL) was treated with sodium thiocyanate (1.0 g, 12.3 mmol) and stirred at room temperature, monitored by TLC. After the reaction was complete, the suspension was filtered, the filter cake was washed with EtOH, and the filtrate was... In a vacuumConcentration. The residue was diluted with water and extracted with tert-butyl methyl ether. The combined organic layers were washed successively with water and brine, dried over anhydrous Na₂SO₄, filtered, and In a vacuum Concentrate to obtain the title compound, which is a brown oily substance, and use it as is in the next step.

[0491] 1 H NMR (400 MHz, CDCl3) δ ppm 4.21 (s, 2 H) 4.05 (s, 1 H) 2.03 - 2.10 (m, 1 H) 1.04 - 1.16 (m, 2H) 0.88 (br s, 2 H)

[0492] Step 2Ab: Preparation of 2-chloro-4-cyclopropyl-thiazole

[0493]

[0494] A sample of (2-cyclopropyl-2-oxo-ethyl)thiocyanate (1.17 g, 7.96 mmol) was treated with hydrogen chloride (11.7 mL, 12.3 g, 47 mmol) in dioxane at 5°C. The reaction mixture was heated to room temperature and stirred for 12 hours. The reaction mixture was poured onto ice and neutralized with a saturated aqueous solution of NaHCO3. The reaction mixture was extracted with EtOAc (3 x 15 mL), and the combined organic layers were dried over anhydrous Na2SO4, filtered, and... In a vacuum The product was concentrated to obtain a crude product. It was then purified by CombiFlash chromatography with elution in cyclohexane:EtOAc to give the title compound as a yellow liquid.

[0495] LCMS (Method B): RT = 1.16 min, 160.0 [M+H]

[0496] Step 2Ac: Preparation of 2-(4-cyclopropylthiazolyl)-2-(1-methylpyrazol-4-yl)propionitrile

[0497] A solution of 2-(1-methylpyrazol-4-yl)propionitrile (5 g, 37 mmol) in THF (50 mL) was cooled to -78°C under nitrogen atmosphere. At -78°C, n-butyllithium (22 mL, 44.38 mmol, 2.0 mol / L, in hexane) was added dropwise to this mixture. The resulting pale green suspension was stirred at this temperature for 10 min and then fractionally treated with 2-chloro-4-cyclopropylthiazole (5.9 g, 36.99 mmol). The resulting green suspension was stirred at -78°C for 5 min and then allowed to warm to room temperature. After stirring at ambient temperature for 16 hr, LCMS showed the reaction was complete. The reaction mixture was slowly quenched at 0°C with an aqueous solution of NH4Cl and then poured into water (50 mL). Extract the mixture with EtOAc (2 x 100 mL), and wash the combined organic layers once with brine (50 mL), dry with anhydrous Na₂SO₄, filter, and In a vacuum Concentration. The crude compound was purified by CombiFlash chromatography with elution of EtOAc / cyclohexane (10%-60%) to obtain the title compound as a light-colored oil.

[0498] LCMS (Method B): RT = 1.08 min, 259.1 [M+H]

[0499] Method B:

[0500] Step 2Ba: Preparation of 2-(4-bromothiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propionitrile

[0501]

[0502] Similar to The above text Step 2Ac is prepared from 4-bromo-2-chloro-thiazole (CAS: [92977-45-2]) and 2-(1-methylpyrazol-4-yl)propionitrile (Step 1, Example P-1).

[0503] LCMS (Method B): RT = 1.07 min, 297.1 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm7.55 (d, J =5.36 Hz, 2 H), 7.23 (s, 1 H), 3.89 - 3.95 (m, 3 H), 2.18 (s, 3 H),

[0504] Step 2Bb: Preparation of 2-(4-cyclopropylthiazolyl)-2-(1-methylpyrazol-4-yl)propionitrile

[0505] Cyclopropylboronic acid (0.254 g, 2.96 mmol) and cesium carbonate (1.754 g, 5.38 mmol) were added to a stirred solution of 2-(4-bromothiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propionitrile in 2-methyl-THF (4 mL) and water (0.67 mL). The reaction mixture was purged with nitrogen for 10 min and then treated with Pd(dppf)Cl2·CH2Cl2 (0.111 g, 0.1346 mmol). The resulting reaction mixture was stirred at 80°C for 6 h and monitored by LCMS. After the reaction was complete, the reaction mixture was quenched with water (20 mL) and filtered through diatomaceous earth. The filtrate was extracted with EtOAc (2 x 30 mL), and the combined organic layers were dried over anhydrous Na2SO4 and... In a vacuum Concentration. The crude product was adsorbed onto silica gel and purified by normal-phase column chromatography (0-50% EtOAc in cyclohexane) to obtain the pure title compound.

[0506] LCMS: - (Method B): RT = 1.09 min, 259.1 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm7.54 (d, J=0.73 Hz, 1 H), 7.50 (s, 1 H), 6.79 (s, 1 H), 3.92 (s, 3 H), 2.14 (s, 3 H),1.98 - 2.05 (m, 1 H), 0.93 (br d, J=18.71 Hz, 4 H)

[0507] Step 3: Preparation of 2-(4-cyclopropylthiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine

[0508]

[0509] Borane and methylthioalkylmethane (7.7 mL, 15.3 mmol) were added dropwise to a stirred solution of 2-(4-cyclopropylthiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propionitrile (1.32 g, 5.11 mmol) in THF (15.3 mL) at room temperature under a nitrogen atmosphere. The resulting reaction mixture was stirred at 60°C for 6 hr, monitored by LCMS. After the reaction was complete, the mixture was cooled to 0°C and treated dropwise with hydrochloric acid (3.42 mL, 20.5 mmol, strong gas escaping!). The mixture was then stirred at 60°C for 1 hr. After cooling to room temperature, the reaction mixture was carefully treated with 6 N NaOH until the mixture reached approximately pH 12. The reaction mixture was extracted with EtOAc (3 x 30 mL), and the combined organic layers were washed once with brine, dried, and In a vacuum Concentrate to obtain 2-(4-cyclopropylthiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine, which is a light brown oil.

[0510] LCMS (Method B): RT = 0.89 min, 263.1 [M+H]

[0511] Step 4: Preparation of methyl 1-(2,4-difluorophenyl)triazole-4-carboxylate:

[0512]

[0513] A solution of 1-azido-2,4-difluorobenzene (CAS: [91229-55-9], 0.30 g, 1.8 mmol) in methanol (3.6 mL) was treated sequentially with anhydrous copper(II) sulfate (0.053 g, 0.33 mmol), sodium ascorbate (0.46 g, 2.3 mmol) in water (3.6 mL), and then with methyl propionate (0.14 g, 0.14 mL, 1.7 mmol). The slightly red reaction mixture was stirred at room temperature for 2 days and monitored by LCMS. After the reaction was complete, the reaction mixture was... In a vacuum The mixture was concentrated, and the residue was absorbed into water and EtOAc. The organic layer was separated, washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under vacuum. The crude product was purified by elution with cyclohexane / EtOAc in a silica gel column (Rf200) to give the title compound as a white solid.

[0514] LCMS (Method B): RT = 0.79 min, 240 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm; 8.59 (d, J=2.57 Hz, 1 H), 7.96 - 8.05 (m, 1 H), 7.09 - 7.17 (m, 2 H), 4.02 (s, 3 H)

[0515] Step 5: Preparation of 1-(2,4-difluorophenyl)triazole-4-carboxylic acid

[0516]

[0517] A solution of methyl 1-(2,4-difluorophenyl)triazole-4-carboxylate (0.31 g, 1.3 mmol) in THF (6.5 mL) and water (3.2 mL) was treated with lithium hydroxide monohydrate (0.047 g, 1.9 mmol) and the mixture was stirred at room temperature. After 3 hours, LCMS showed the desired mass and consumption of starting material. The THF was evaporated under vacuum, and the remaining aqueous residue was acidified with 2 N HCl (approximately 0.5 mL). The resulting pale red suspension was filtered, and the white filter cake was washed with water and cyclohexane and treated at 55°C. In a vacuum Dry to give 1-(2,4-difluorophenyl)triazole-4-carboxylic acid as a white solid.

[0518] LCMS (Method B): RT = 0.63 min, RT = 0.79 min; 1 H NMR (400 MHz, DMSO-d6) δppm 7.27 - 7.52 (m, 1 H), 7.73 (ddd, J=11.10, 8.71, 2.57 Hz, 1 H), 7.95 (td,J=8.80, 5.87 Hz, 1 H), 9.15 (d, J=1.47 Hz, 1H), 13.26-13.60 (bs,1H).

[0519] Step 6: N -[2-(4-Cyclopropylthiazolyl-2-yl)-2-(1-Methylpyrazole-4-yl)propyl]-1-(2,4-Difluorobenzene) Preparation of triazole-4-carboxamide (compound P-2, Table P)

[0520] 1-(2,4-difluorophenyl)triazol-4-carboxylic acid (1.5 equivalents, 0.6 mmol) was dissolved in 1.5 mL of N,N-dimethylacetamide. The solution was treated with DIPEA (6 equivalents, 2.4 mmol) and stirred at room temperature for 10 min. 2-(4-cyclopropylthiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine (1 equivalent, 0.04 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylureon hexafluorophosphate (2 equivalents, 0.8 mmol) were added, and the reaction mixture was stirred at room temperature for 8 hr. The crude sample was transferred to the wells of a 24-well plate, diluted with 1.5 mL of MeOH, and then purified by reversed-phase preparative HPLC. Purification was performed using 50 mL flow purifiers (two injections per sample). All fractions were analyzed by UPLC-MS (50 µL aliquots diluted in 100 µL acetonitrile), then concentrated and... In a vacuum Concentration. Dissolve the fraction containing the desired product in acetonitrile and transfer it to the final target container. Perform final quality control of the product, then concentrate by evaporation (amplify into 10 µL portions and dilute in 100 µL of acetonitrile). Confirm the expected quality by UPLC-MS (Method A).

[0521] LCMS (Method A): RT = 1.58 min, 470.2 [M+H];

[0522] Example P2: N -[2-(2-bromothiazolyl-4-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorobenzene) Preparation of 5-tetrazolium-5-carboxamide (compound P-4, Table P)

[0523] Compound P-4, Table P

[0524] Step 1: Preparation of (2E)-2-(p-Toluenesulfonylhydrazine)ethyl acetate

[0525]

[0526] A solution of 4-methylbenzenesulfonyl hydrazine (CAS: 1576-35-8, 2 g, 10.7 mmol) in ethanol (40 mL) was treated with ethyl 2-oxoacetate (2.63 g, 12.8 mmol) at room temperature. The reaction mixture was stirred for 1 hour and then subjected to... exist In a vacuum The ethanol was concentrated to remove the residue. The resulting residue was diluted with water and extracted with EtOAc. The organic phase was separated, and the solvent was evaporated under vacuum to give ethyl (2E)-2-(p-toluenesulfonylhydrazine)acetate, which was used as is in the next step.

[0527] LCMS (Method B): RT = 1.06 min, 271 [M+H]; 1H NMR (400 MHz, CDCl3) δ ppm9.31 (s, 1 H), 7.85 (d, J =8.31 ​​Hz, 2 H), 7.34 (d, J =8.07 Hz, 2 H), 7.23 (s, 1H), 4.27 (q, J =7.09 Hz, 2 H), 2.44 (s, 3 H) 1.23 - 1.37 (m, 3 H).

[0528] Step 2: Preparation of ethyl 2-(2,4-difluorophenyl)tetrazole-5-carboxylate

[0529]

[0530] A solution of 2,4-difluoroaniline (1.00 g, 7.74 mmol) in 6 M hydrochloric acid in deionized water (6 mL, 36 mmol) and ethanol (5 mL) was cooled to 0°C. Sodium nitrite (0.64 g, 9.29 mmol) was added to this solution, and the resulting solution was stirred for 1 hr, and then added dropwise to a solution of (2E)-2-(p-toluenesulfonylhydrazine)ethyl acetate (2.3 g, 8.51 mmol) in pyridine (20 mL) at -20°C. The reaction mixture was slowly heated to room temperature and then stirred for 5 hours. The resulting mixture was diluted with 1 N HCl, and the aqueous layer was extracted with EtOAc (X 3). The combined organic layers were dried over anhydrous Na₂SO₄ and… In a vacuum The crude product was concentrated and purified by column chromatography by elution with 30% EtOAc in hexane to obtain ethyl 2-(2,4-difluorophenyl)tetrazole-5-carboxylate, which is a slightly reddish oil.

[0531] 1 H NMR (400 MHz, CDCl3) δ ppm 7.86 - 7.94 (m, 1 H), 7.11 - 7.21 (m, 2H), 4.60 (q, J=7.21 Hz, 2 H), 1.51 (t, J=7.13 Hz, 3 H)

[0532] Step 3: Preparation of 2-(2,4-difluorophenyl)tetrazole-5-carboxylic acid

[0533]

[0534] Lithium hydroxide monohydrate (0.376 mg, 15.736 mmol) was added to a stirred solution of ethyl 2-(2,4-difluorophenyl)tetrazole-5-carboxylate (1 g, 3.93 mmol) in THF (10 mL) and water (5 mL), and the resulting mixture was stirred at room temperature for 30 min. After the reaction was complete, the mixture was cooled and acidified with 2 N HCl aqueous solution. The aqueous layer was extracted with EtOAc (X 3), and the combined organic layers were dried over anhydrous Na2SO4 and... In a vacuum Concentrate to obtain the title compound in solid form.

[0535] LCMS (Method B): RT = 0.35 min, 227.1 [M+H]; 1 H NMR (400 MHz, DMSO-d6) δ ppm8.06 - 8.13 (m, 1 H) 7.80 (ddd, J=11.13, 8.80, 2.69 Hz, 1 H) 7.42 - 7.49 (m,1 H) 2.48 - 2.52 (m, 5 H)

[0536] Step 4: Preparation of (2-bromothiazol-4-yl)-(1-methylpyrazol-4-yl)methanol

[0537]

[0538] A solution of 4-iodo-1-methylpyrazole (CAS: [39806-90-1], 2.00 g, 9.62 mmol) in THF (40 mL) was cooled to 0°C and treated dropwise with a solution of isopropyl magnesium chloride-lithium chloride complex in THF (1.3 mol / L) (11 mL, 14.4 mmol). After stirring at 0°C for 30 min, a solution of 2-bromothiazol-4-carboxaldehyde (CAS: [5198-80-1], 2.77 g, 14.4 mmol) in THF (5 mL) was added, and the reaction mixture was then heated to room temperature and stirred for 1 hr (after which the reaction was complete, as shown by LCMS analysis). The reaction mixture was quenched with a saturated aqueous solution of NH4Cl (40 mL), diluted with water, and extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and In a vacuum Concentrate to obtain the title compound in solid form.

[0539] LCMS (Method B): rt: = 0.40 min, 273.1 [M+H]

[0540] Step 5: Preparation of 2-(2-bromothiazolyl-4-yl)-2-(1-methylpyrazol-4-yl)acetonitrile

[0541]

[0542] A solution of (2-bromothiazol-4-yl)-(1-methylpyrazol-4-yl)methanol (2.2 g, 8.0 mmol) in acetonitrile (48 mL) was treated with lithium carbonate (0.12 g, 1.6 mmol), trimethylsilyl cyanide (4.9 mL, 36 mmol), and iodine (3.7 g, 14 mmol) at room temperature. The resulting mixture was stirred at 60°C for 4 hours and then cooled to room temperature and poured into a saturated aqueous solution of sodium thiosulfate. The mixture was extracted with EtOAc (2 x 80 mL), and the combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and... In a vacuum The product was concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography using 0-40% EtOAc in cyclohexane as the eluent to obtain the title compound.

[0543] LCMS (Method B): RT = 1.02 min, 282 [M+H];

[0544] Step 6: Preparation of 2-(2-bromothiazol-4-yl)-2-(1-methylpyrazol-4-yl)propionitrile

[0545]

[0546] A solution of 2-(2-bromothiazolyl-4-yl)-2-(1-methylpyrazol-4-yl)acetonitrile (1.3 g, 4.6 mmol) in THF (14 mL) was cooled to -78°C under argon atmosphere and treated dropwise with sodium bis(trimethylsilyl)amino (1.0 mol / L) (5.1 mL, 5.1 mmol) in THF. The resulting suspension was stirred at this temperature for 25 min and then treated with methyl iodide (0.31 mL, 5.1 mmol). The resulting solution was stirred at -78°C for 5 min, allowed to warm to room temperature, and then stirred for another 30 min. The reaction mixture was then cooled to 0°C and quenched with an aqueous solution of NH4Cl (20 mL). The mixture was extracted with EtOAc (2 × 30 mL), the combined organic phases were dried over anhydrous Na2SO4, filtered, and In a vacuum Concentration. The crude product was purified by silica gel column chromatography using 0-20% EtOAc in cyclohexane as the eluent to obtain the title compound.

[0547] LCMS (Method B): RT = 1.02 min, 296 [M+H];

[0548] Step 7: Preparation of 2-(2-bromothiazol-4-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine

[0549]

[0550] At 0°C, DIBAL-H (1.0 mol / L) (5 mL, 5 mmol) in toluene was added to a stirred solution of 2-(2-bromothiazo-4-yl)-2-(1-methylpyrazol-4-yl)propionitrile (2 mmol, 0.5 g) in dichloromethane (20 mL) and stirred for 5 min. This mixture was then added to a suspension of sodium borohydride (0.3 g, 7 mmol) in THF (8 mL) and methanol (20 mL) at 0°C and stirred slowly at room temperature for 1 h. After the reaction was complete, the reaction mixture was quenched with a saturated aqueous ammonium chloride solution (20 mL) and stirred for another 30 min. A 10% aqueous NaOH solution (10 mL) was added, and the mixture was extracted with dichloromethane (25 mL × 2). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered, and... In a vacuum Concentrate to obtain 2-(2-bromothiazol-4-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine, which is a brown oil.

[0551] LCMS (Method B): RT = 0.21 min, 301 [M+H]

[0552] Step 8: N -[2-(2-bromothiazolyl-4-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorophenyl) Preparation of tetrazolium-5-carboxamide (compound P-4, Table P)

[0553] In a dry 50 mL RBF equipped with a nitrogen inlet, 2-(2,4-difluorophenyl)tetrazole-5-carboxylic acid (0.06 g, 0.3 mmol) and 2-(2-bromothiazol-4-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine (0.09 g, 0.2 mmol, 80 wt%) were suspended in EtOAc (1 mL). DIPEA (0.1 mL, 0.7 mmol) and T3P (50 wt%) in EtOAc (0.4 mL, 0.7 mmol, 50 wt%) were added to this mixture at 0°C, and the reaction mixture was stirred at room temperature for 3 hours. The progress of the reaction was monitored by LCMS and TLC. After the reaction was complete, the reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2 × 25 mL). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel adsorption and by combi flash chromatography using 0-60% EA in cyclohexane as the eluent to obtain a dark brown gel-like product.

[0554] LCMS (Method B): RT = 1.10 min, 509 [M+H];1 H NMR (400 MHz, CDCl3) δ ppm 7.98(br t, J=5.69 Hz, 1 H) 7.95 - 7.85 (m, 1 H) 7.40 (s, 1 H) 7.31 - 7.36 (m, 1H) 7.19 - 7.09 (m, 2 H) 6.98 (s, 1 H) 4.17 - 4.10 (m, 1 H) 4.03 (br d, J=6.24Hz, 1 H) 3.88 (s, 3 H) 1.74 (s, 3 H)

[0555] Example P3: N -[2-(4,5-dichlorothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluoro Preparation of phenyl)tetrazole-5-carboxamide (compound P-3, Table P)

[0556] Compound P-3, Table P

[0557] Step 1: Preparation of 2-(4,5-dichlorothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propionitrile

[0558]

[0559] A solution of 2-(1-methylpyrazol-4-yl)propionitrile (0.400 g, 2.96 mmol) in THF (12 mL) was cooled to -78°C. A solution of n-butyllithium (1.2 mL, 2.6 mmol, 2.5 N, in hexane) was added dropwise, and the resulting pale brown suspension was stirred at this temperature for 10 min, followed by the addition of 2,4,5-trichlorothiazol (CAS 50844-30-9, 0.558 g, 2.96 mmol). The resulting suspension was stirred at -78°C for 5 min, then warmed to room temperature and stirred under argon for 30 min. The reaction mixture was poured into water and extracted twice with some EtOAc. The combined organic layers were washed once with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was purified by rapid chromatography using EtOAc and cyclohexane as eluents to obtain the title compound.

[0560] LCMS (Method E): RT = 0.95 min, 287 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm2.1 (s, 3 H) 3.9 (s, 3 H) 7.6 (d, J =3 Hz, 2 H)

[0561] Step 2: Preparation of 2-(4,5-dichlorothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine

[0562]

[0563] Sodium borohydride (0.069 g, 1.7 mmol) was added in small portions to a solution of 2-(4,5-dichlorothiazo-2-yl)-2-(1-methylpyrazol-4-yl)propionitrile (0.20 g, 0.70 mmol) and cobalt dichloride (0.092 g, 0.70 mmol) in methanol (2.3 mL) at 0°C (Note: violent reaction with hydrogen release!). A black precipitate was observed to form immediately, and the mixture was stirred at 0°C for 1 h. After this time, 1 M HCl was added until the pH reached 3–4, and the mixture was extracted three times with DCM to remove impurities. Extraction was difficult due to the presence of a persistent emulsion, and further addition of DCM and brine was made to enhance separation. The pH of the aqueous phase was adjusted to 10 with 2 M NaOH, and the mixture was extracted with DCM (a large amount of DCM was added to further enhance the separation of the two phases). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to obtain the title compound.

[0564] LCMS (Method E): RT = 0.57 min, 291 [M+H]

[0565] Step 3: N -[2-(4,5-dichlorothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorobenzene) Preparation of 5-Tetrazolium-5-carboxamide

[0566] At room temperature, 2-(4,5-dichlorothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine (0.20 g, 0.69 mmol) was added to a solution of 2-(2,4-difluorophenyl)tetrazole-5-carboxylic acid (0.155 g, 0.69 mmol) in EtOAc (6.0 mL). DIPEA (0.480 mL, 2.747 mmol) and 1-propanephosphonic anhydride (1.022 mL, 1.717 mmol) were added to this mixture at 0°C, and the reaction mixture was stirred at room temperature for 16 h. After the reaction was complete, the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel adsorption and by CombiFlash using 0-80% EtOAc in cyclohexane as the eluent to obtain the desired product N-[2-(4,5-dichlorothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorophenyl)tetrazole-5-carboxamide.

[0567] LCMS (Method B): RT = 1.18 min, 499.0 [M+H]; 1H NMR (400 MHz, CDCl3) δ ppm8.05 (br t, J=6.07 Hz, 1 H), 7.87 - 7.95 (m, 1 H), 7.48 (s, 1 H), 7.42 (s, 1H), 7.10 - 7.20 (m, 2 H), 4.09 - 4.20 (m, 2 H), 3.92 (s, 3 H), 1.82 (s, 3 H); 19 F NMR (377 MHz, CDCl3) δ ppm -103.47 (s, 1 F), -103.49 (s, 1 F), -114.74 (s, 1 F), -114.76 (s, 1 F)

[0568] Example P4: N-[2-(4-bromothiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorophenyl) Preparation of tetrazolium-5-carboxamide (compound P-12, Table P)

[0569] Compound P-12, Table P

[0570] Step 1: Preparation of 2-(4-bromothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine

[0571]

[0572] Similar to the method described in step 3 of Example P1, a sample of 2-(4-bromothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propionitrile (prepared as described in step 2Ba of Example 1) is reduced to 2-(4-bromothiazol-2-yl)-2-(1-methylpyrazol-4-yl)prop-1-amine.

[0573] LCMS (Method D) RT = 0.39 min, 302 [M+H].

[0574] Step 2: N-[2-(4-bromothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorophenyl)- Preparation of tetrazolium-5-carboxamide (compound P-12, Table P)

[0575] The title compound was prepared by coupling 2-(4-bromothiazol-2-yl)-2-(1-methylpyrazol-4-yl)prop-1-amine with 2-(2,4-difluorophenyl)tetrazole-5-carboxylic acid (prepared as described in step 3 of Example 2) using the general coupling conditions described in step 6 of Example P-1.

[0576] LCMS (Method D), RT = 1.04 min, 509.2 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm8.26 (br t, J=6.13 Hz, 1 H), 7.87 - 7.97 (m, 1 H), 7.47 (s, 1 H), 7.40 (s, 1H), 7.05 - 7.22 (m, 3 H), 4.16 (d, J =6.50 Hz, 2H), 3.91 (s, 3H), 1.85 (s, 3H); 19 F NMR (377 MHz, CDCl3) δ ppm -103.63 (s, 1 F), -114.67 (s, 1 F)

[0577] Example P5: N -[2-(4-cyanothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorobenzene) Preparation of tetrazolium-5-carboxamide (compound P-8, Table P)

[0578] (Compound P-8, Table P)

[0579] A solution of N-[2-(4-bromothiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorophenyl)tetrazol-5-carboxamide (0.0500 g, 0.0982 mmol) and zinc cyanide (0.0235 g, 0.196 mmol) in DMF (0.491 mL) was degassed under nitrogen for 10 min, treated with tetrakis(triphenylphosphine)palladium (0.0115 g, 0.00982 mmol), and stirred in a microwave at 120°C for 2 h. After this time, LCMS analysis showed that the reaction was complete. The mixture was diluted with water and extracted with EtOAc (X 3). The combined organic layers were dried over anhydrous Na2SO4 and In a vacuum Concentration. The crude compound was purified by CombiFlash using EtOAc in cyclohexane as the eluent, and then further purified by reversed-phase column chromatography using CH3CN in water as the eluent to obtain the title compound.

[0580] LCMS (Method D): RT = 1.03 min, 456.4 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm8.07 (br t, J=6.42 Hz, 1 H), 7.97 (s, 1 H), 7.90 (td, J=8.62, 5.62 Hz, 1 H), 7.44 (s, 1 H), 7.41 (s, 1 H), 7.09 - 7.18 (m, 2 H), 4.17 (dd, J=6.54, 2.63Hz, 2 H), 3.91 (s, 3 H), 1.87 (s, 3 H);19 F NMR (377 MHz, CDCl3) δ ppm -103.45(s, 1 F), -103.48 (s, 1 F), -114.74 (s, 1 F), -114.77 (s, 1 F)

[0581] Example P6: N -[2-(4-Cyclopropylthiazolin-2-yl)-2-(1-Methylpyrazole-4-yl)propyl]-1-(3,5-Difluoro- Preparation of 2-pyridyl)triazole-4-carboxamide (compound P-1, Table P)

[0582] (Compound P-1, Table P)

[0583] Step 1: Preparation of 2-azido-3,5-difluoropyridine

[0584]

[0585] A solution of 3,5-difluoropyridin-2-amine (CAS: [732306-31-9], 500 mg, 3.84 mmol) in acetonitrile (15 mL) was cooled to 0°C and treated dropwise with tert-butyl nitrite (0.660 mL, 4.9962 mmol), followed by trimethyl azidosilane (0.593 mL, 4.4197 mmol). The resulting solution was warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with water and extracted with diethyl ether (X 3). The combined organic layers were washed with water and brine, dried over anhydrous Na₂SO₄, and... In a vacuum Concentrate to obtain the title compound.

[0586] Step 2: Preparation of methyl 1-(3,5-difluoro-2-pyridyl)triazole-4-carboxylate

[0587]

[0588] A solution of 2-azido-3,5-difluoropyridine (5.5 g, 35 mmol) in methanol (66 mL) was stirred under a nitrogen atmosphere and treated with anhydrous copper sulfate (1.0 g, 6.3 mmol), water (66 mL), sodium ascorbate (8.8 g, 44 mmol), and methyl propionate (2.7 mL, 32 mmol). The reaction mixture was stirred at room temperature for 15 hours, and TLC analysis showed that the reaction was complete. In a vacuum Concentration. The residue was dissolved in EtOAc and washed with water and brine. The organic layer was dried over anhydrous MgSO4, filtered, and In a vacuum Concentration. The crude product was purified by silica gel chromatography to obtain the title compound.

[0589] LCMS (Method D): RT = 0.79 min, 241.1 [M+H]; 1H NMR (400 MHz, CDCl3) δ ppm8.80 (s, 1 H) 8.35 (d, J=2.32 Hz, 1 H) 7.60 (ddd, J=9.38, 7.24, 2.32 Hz, 1 H)4.01 (s, 3 H)

[0590] Step 3: Preparation of lithium 1-(3,5-difluoro-2-pyridyl)triazole-4-carboxylate

[0591]

[0592] At room temperature, lithium hydroxide monohydrate (0.93 g, 22 mmol) was added to a solution of methyl 1-(3,5-difluoro-2-pyridyl)triazole-4-carboxylate (5.3 g, 22 mmol) in THF (55 mL) and water (22 mL). The resulting reaction mixture was stirred at room temperature for 18 hr. After the reaction was complete, the organic solvent was removed. In a vacuum The residue was removed, and the compound was dried by azeotropic drying with toluene. The title compound was obtained as a white solid.

[0593] LCMS; (Method B), RT = 0.43 min, 227.0 [M+H]; 1 H NMR (400 MHz, DMSO-d6) δppm 8.61 (d, J=2.50 Hz, 1 H), 8.52 (s, 1 H), 8.41 (ddd, J=10.35, 8.29, 2.50Hz, 1 H); 19 F NMR (377 MHz, DMSO-d6) δ ppm -122.05 (s, 1 F), -122.12 (s, 1 F)

[0594] Step 4: N -[2-(4-Cyclopropylthiazolin-2-yl)-2-(1-Methylpyrazole-4-yl)propyl]-1-(3,5-Difluoro- Preparation of 2-pyridyl)triazole-4-carboxamide (compound P-1, Table P)

[0595] Similar to the coupling method described in step 6 of Example 1, it is prepared by reacting lithium 1-(3,5-difluoro-2-pyridyl)triazole-4-carboxylate with 2-(4-cyclopropylthiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine.

[0596] LCMS (Method A); RT = 1.45 min, 471.8 [M+H]

[0597] Example P7: N -[2-(4-bromothiazolyl-2-yl)-2-(1-methylpyrazol-4-yl)propyl]-2-(2,4-difluorophenyl) Preparation of triazole-4-carboxamide (compound P-9, Table P)

[0598] Compound P-9, Table P

[0599] Step 1: Preparation of ethyl 2-[(2,4-difluorophenyl)hydrazine]-3-oxo-propionate

[0600]

[0601] A solution of 2,4-difluoroaniline (4.00 g, 30.9 mmol) in water (32 mL) and hydrogen chloride (12 mL, 35%) was cooled to 0°C and treated with sodium nitrite (2.56 g, 37.1 mmol) in water (32 mL). The mixture was stirred at 0°C for 5 min. In a separate reaction vessel, a solution of ethyl 3-(dimethylamino)prop-2-enoate (12.0 g, 23.4 mmol) and potassium acetate (4.61 g, 46.4 mmol) in ethanol (40 mL) was cooled to 0°C and then added to the above diazotization solution at 0°C. The reaction mixture was then heated to room temperature and stirred for 12 hr. After this time, LCMS analysis showed that the reaction was complete. The reaction mixture was diluted with water and extracted with EtOAc (50 mL × 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and... In a vacuum Concentrate to obtain the title compound, which is then used as is in the next step.

[0602] LCMS (Method B): RT = 1.09 min, 257 [M+H]

[0603] Step 2: Preparation of ethyl 2-[(2,4-difluorophenyl)hydrazinyl]-3-oxime-propionate

[0604]

[0605] Potassium acetate (1.45 g, 14.6 mmol) and hydroxylamine hydrochloride (0.49 g, 7.02 mmol) were added to a solution of ethyl 2-[(2,4-difluorophenyl)hydrazine]-3-oxopropionate (3.00 g, 5.85 mmol) in ethanol (30 mL). The reaction mixture was stirred at 80°C for 2 hr, followed by LCMS showing complete conversion to the desired product. The reaction mixture was cooled, diluted with water, and extracted with EtOAc (50 mL × 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and... exist In a vacuum Concentrate to obtain the title compound, which is then used as is in the next step.

[0606] LCMS (Method B): RT = 1.16 min, 272 [M+H]

[0607] Step 3: Preparation of ethyl 2-(2,4-difluorophenyl)triazole-4-carboxylate

[0608]

[0609] A solution of ethyl 2-[(2,4-difluorophenyl)hydrazine]-3-oxime-propionate (3.4 g, 6.3 mmol) in EtOAc (34 mL, 10 mL / g) was stirred at 140°C for 1 hr in a sealed container, monitored by LCMS. After the reaction was complete, the mixture was cooled, diluted with brine, and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4 and... In a vacuum Concentration. The crude product was purified by CombiFlash using EtOAc:cyclohexane as the eluent (5:95) to give ethyl 2-(2,4-difluorophenyl)triazole-4-carboxylate as a brown solid.

[0610] LCMS (Method D): RT = 1.19 min, [M+H]

[0611] Step 4: Preparation of lithium 2-(2,4-difluorophenyl)triazole-4-carboxylate

[0612]

[0613] Lithium hydroxide (11.0 mg, 0.47 mmol) was added to a stirred solution of ethyl 2-(2,4-difluorophenyl)triazole-4-carboxylate (0.10 g, 0.31 mmol) in THF (0.4 mL) and water (0.1 mL), and the reaction mixture was stirred at room temperature for 3 hours. After the reaction was complete, the reaction mixture was concentrated, and the residue was milled with TBME and filtered. The filtered solid was... In a vacuum The compound was dried to obtain the title compound as a white solid.

[0614] LCMS (Method B): RT = 0.29 min, 224 [MH]

[0615] Step 5: N -[2-(4-bromothiazolyl-2-yl)-2-(1-methylpyrazole-4-yl)propyl]-2-(2,4-difluorophenyl)- Preparation of triazole-4-carboxamide (compound P-9, Table P)

[0616] At 0°C, a suspension of lithium 2-(2,4-difluorophenyl)triazol-4-carboxylate (0.115 g, 0.4980 mmol) in EtOAc (4.5 mL) was treated with 2-(4-bromothiazol-2-yl)-2-(1-methylpyrazol-4-yl)propyl-1-amine (0.150 g, 0.498 mmol), DIPEA (0.263 g, 0.348 mL, 1.99 mmol), and 1-propanephosphonic anhydride (0.792 g, 0.741 mL, 1.25 mmol). The reaction mixture was heated to room temperature and stirred for 16 hr. After this time, TLC and LCMS analysis showed that the reaction was complete. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2 × 20 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered, and In a vacuum Concentration. The crude product was purified by silica gel adsorption and by CombiFlash using 0-80% EtOAc in cyclohexane as the eluent to obtain the title product, which is a yellow gel.

[0617] LCMS (Method B): RT = 1.14 min, 508 [M+H]; 1 H NMR (400 MHz, CDCl3) δ ppm8.39 (s, 1 H), 8.04 (br d, J =9.41 Hz, 1 H), 8.00 (d, J =7.27 Hz, 1 H), 7.55(s, 1 H), 7.47 (s, 1 H), 7.36 (s, 1 H), 7.13 - 7.21 (m, 2 H), 4.15 (t, J =6.05Hz, 2H), 3.99 (s, 3H), 1.91 (s, 3H); 19 F NMR (377 MHz, CDCl3) δ ppm -107.32(s, 1 F), -107.34 (s, 1 F), -116.52 (s, 1 F), -116.54 (s, 1 F)

[0618] Examples of synthesized compounds having formula (I) (along with analytical data) are shown in Table P.

[0619] Table P: Synthesized compounds and their spectroscopic and physicochemical data.

[0620]

[0621] Biological examples

[0622] Example B1: Alternaria solani / Tomato / Leaf round spots (early blight)

[0623] Tomato leaf disc cultivar Baby was placed on agar in a multi-well plate (24-well size) and sprayed with a prepared test compound diluted in water. Two days after application, the leaf discs were inoculated with a suspension of fungal spores. The inoculated leaf discs were cultured in a climate chamber under a 12 / 12 h (light / dark) light program, at 23°C / 21°C (day / night) and 80% rh, and the activity of the compounds was assessed as the percentage of disease control compared to untreated leaf discs when an appropriate level of disease damage was observed (5 to 7 days after application). The following compounds provided at least 80% control of Alternaria solanacearum at 200 ppm compared to the untreated control, which showed extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-8, P-10, P-11, P-12, P-13, and P-14.

[0624] Example B2: Botryotinia fuckeliana (Botryotinia flavescens) Liquid culture (gray) mildew)

[0625] Fungal conidia from frozen storage were directly mixed into nutrient broth (Vogels broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 3–4 days after application. The following compounds at 20 ppm provided at least 80% control of *Botrytis cinerea* compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-10, P-11, P-12, and P-13.

[0626] Example B3: Small clusters of quail (Anthracnose fungus of cucurbitaceae) Colletotrichum lagenarium Liquid culture (carbon) gangrene

[0627] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was measured photometrically 3–4 days after application. The following compounds at 20 ppm provided at least 80% control of *Trichophyton cucumeris* compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-10, P-11, and P-12.

[0628] Example B4: Blumeria graminis f. sp. tritici (wheat powdery mildew fungus) (Erysiphe graminis f. sp. tritici)) / Wheat / Leaf disc preventative (for powdery mildew on wheat)

[0629] Wheat leaf section cultivar Kanzler was placed on agar in multi-well plates (24-well size) and sprayed with a prepared test compound diluted in water. One day after application, leaf discs were inoculated by shaking powdery mildew-infected plants over these test plates. The inoculated leaf discs were cultured in a climate chamber at 20°C and 60% rh under a light scheme of 24 h darkness followed by 12 h light / 12 h darkness, and the activity of the compounds was assessed as the percentage of disease control compared to untreated control when an appropriate level of disease damage was observed on untreated test leaf sections (6 to 8 days after application). The following compounds, at 200 ppm, provided at least 80% control of wheat powdery mildew when compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-8, P-10, P-11, P-12, P-13, and P-14.

[0630] Example B5: Fusarium oxysporum Liquid culture (Fusarium head blight)

[0631] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 3–4 days after application. The following compounds, at 20 ppm, provided at least 80% control of *Fusarium oxysporum* compared to an untreated control showing extensive disease development under the same conditions: P-1, P-5, P-11, and P-13.

[0632] Example B6: wheat glume blight fungus (Clerodendrum cyrtomata () Septoria nodorum Wheat leaf disc preventative (Glume leaf blight)

[0633] Wheat leaf cultivar Cansler was placed on agar in a multi-well plate (24-well size) and sprayed with a prepared test compound diluted in water. Two days after application, leaf discs were inoculated with a suspension of fungal spores. The inoculated test leaf discs were cultured in a climate chamber under a 12-h light / 12-h dark light scheme at 20°C and 75% rh, and the activity of the compounds was assessed as the percentage of disease control compared to untreated leaf discs when an appropriate level of disease damage was observed (5 to 7 days after application). The following compounds provided at least 80% control of *Brachys gleynostemma pentaphyllum* at 200 ppm compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-8, P-10, P-11, P-12, P-13, and P-14.

[0634] Example B7: Monographella nivalis (Snow Mold Leaf Blight) Liquid culture (cereal roots) (rot disease)

[0635] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 4–5 days after application. The following compounds provided at least 80% control of *Clostridium nivale* at 20 ppm compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-10, P-11, P-12, and P-13.

[0636] Example B8: Mycosphaerella arachidis (Mycosphaerella arachidis) Liquid culture (Early leaf spot disease)

[0637] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 4–5 days after application. The following compounds, at 20 ppm, provided at least 80% control of *Gnaphalium affine* at 20 ppm compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-5, P-7, P-10, P-11, P-12, and P-13.

[0638] Example B9: Wheat rust fungus (Puccinia recondita f. sp. tritici) / wheat / leaf disc Therapeutic (brown rust)

[0639] Wheat leaf segments of the cultivar Cansler were placed on agar in multi-well plates (24-well size). The leaf segments were inoculated with a suspension of fungal spores. The plates were stored in the dark at 19°C and 75% rh. One day after inoculation, a prepared test compound diluted in water was applied. The leaf segments were cultured in a climate chamber at 19°C and 75% rh under a 12-h light / 12-h dark light scheme, and the activity of the compound was assessed as the percentage of disease control compared to untreated leaf segments when an appropriate level of disease damage was observed (6 to 8 days after application). The following compounds, P-8 and P-13, provided at least 80% control against *Cryptococcus cryptidis* at 200 ppm when compared to an untreated control showing extensive disease development under the same conditions.

[0640] Example B10: Rice blast fungus (Magnaporthe grisea) ( Inari spores Liquid culture (rice blast)

[0641] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 3–4 days after application. The following compounds, P-1 and P-2, provided at least 80% control of *Strombus rice* at 20 ppm compared to an untreated control showing widespread disease development under the same conditions.

[0642] Example B11: Pyrenophora teres / Barley / Leaf round leaf prevention (net blotch)

[0643] Barley leaf segments of the Hasso cultivar were placed on agar plates (24-well size) and sprayed with a test compound diluted in water. Two days after application, the leaf segments were inoculated with a suspension of fungal spores. The inoculated leaf segments were cultured in a climate chamber under a 12-h light / 12-h dark light scheme at 20°C and 65% rh, and the activity of the compounds was assessed as disease control compared to untreated control leaf segments when an appropriate level of disease damage was observed (5 to 7 days after application). The following compounds provided at least 80% control of *Rhizoctonia solani* at 200 ppm compared to untreated controls showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-8, P-10, P-11, P-12, P-13, and P-14.

[0644] Example B12: Sclerotinia sclerotiorum Liquid culture (cottonymyelitis)

[0645] Mycelial fragments of newly grown liquid cultures of the fungus were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing the fungal material was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 3–4 days after application. The following compounds, at 20 ppm, provided at least 80% control of *Sclerotinia sclerotiorum* compared to an untreated control showing extensive disease development under the same conditions: P-5, P-12, and P-13.

[0646] Example B13: Gramineae (wheat shell needle) Liquid culture (Septoria blotch)

[0647] Fungal conidia from frozen storage were directly mixed into nutrient broth (PDB potato dextrose broth). Nutrient broth containing fungal conidia was added after a solution of the test compound (DMSO) was placed in a microtiter plate (96-well size). The test plate was incubated at 24°C, and growth inhibition was determined photometrically 4–5 days after application. The following compounds provided at least 80% control of *Cyclocarya granatum* at 20 ppm compared to an untreated control showing extensive disease development under the same conditions: P-1, P-2, P-3, P-4, P-5, P-7, P-10, P-11, P-12, and P-13.

Claims

1. A compound having formula (I): (I) in R 1 Selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-ynyl, or C3-C6-cycloalkyl; R 2 Selected from hydrogen, halogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C-C1-C4-alkyl-carbonimide, N-hydroxy-C-C1-C4-alkyl-carbonimide, or C1-C4-alkoxycarbonyl; R 3 Selected from hydrogen, halogens, or C1-C4-alkyl groups; R 4 Selected from hydrogen, halogen, cyano, C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C1-C4-alkylaminocarbonyl, or N,N-di(C1-C4alkyl)aminocarbonyl; R 5 and R 6 Independently selected from hydrogen or C1-C4-alkyl; A 1 Selected from CR 7 Or N, A 2 Selected from CR 8 Or N; A 3 Selected from CR 9 Or N; R 7 R 8 R 9 It is independently selected from hydrogen, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, or C1-C4-haloalkyl; B 1 B 2 B 3 Independently selected from CR 10 , N, NR 11 O, or S, provided that B is a B 1 B 2 B 3 No more than one of them is O or S; R 10 Selected from hydrogen, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C2-C4-enoxy, C2-C4-alkynoxy, C1-C4-alkylthioalkyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, C1-C4-alkoxy-C1-C4-alkyl, NC 1- C4-alkylamino, N,N-di-(C 1- C4-alkyl)amino, C1-C4-alkoxycarbonyl, C1-C4-alkylcarbonyl, N-C1-C4-alkoxy-C1-C4-alkyl-carbonimide, N-hydroxy-C1-C4-alkyl-carbonimide, hydroxy, amino, trifluoromethanesulfonyloxy, cyano, carboxyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl contains 1, 2, 3 or 4 heteroatoms individually selected from N, O or S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl and C3-C6-cycloalkyl is unsubstituted or substituted by 1, 2 or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, or C1-C4-alkoxy; R 11 Selected from hydrogen or C1-C4-alkyl; and Z 1 The group is selected from C1-C4 alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any one of the 5- or 6-membered heteroaryl groups contains 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, provided that no more than one is O or S; and wherein any one of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl groups is unsubstituted or substituted by 1, 2, or 3 substituents independently selected from: halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthioalkyl, C1-C4-alkylsulfinyl, C1-C4-alkylsulfonyl, or C2-C4-alkynyl; Or its agriculturally chemically acceptable salt, stereoisomer, enantiomer, tautomer, or N-oxide.

2. The compound having formula (I) according to claim 1, wherein, R 4 It is hydrogen or methyl, and R 5 and R 6 It is hydrogen.

3. The compound having formula (I) according to claim 1 or claim 2, wherein, R 1 It is a C1-C3-alkyl or a C3-C6-cycloalkyl.

4. The compound having formula (I) according to any one of claims 1 to 3, wherein, R 2 It is hydrogen, halogen, C1-C3-alkyl, or cyclopropyl.

5. The compound having formula (I) according to any one of claims 1 to 4, wherein, A 1 Is it CH or N, A 2 It is CH or N; and A 3 It is CH or N.

6. The compound having formula (I) according to any one of claims 1 to 5, wherein, B 1 B 2 B 3 Independently selected from CR 10 N, O, or S, provided that B is a given. 1 B 2 B 3 No more than one of them is O or S; and R is among them. 10 It is hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl.

7. The compound having formula (I) according to any one of claims 1 to 6, wherein, Z 1 It is a C1-C3-alkyl, phenyl, 5- or 6-membered heteroaryl, or C3-C6-cycloalkyl; wherein any of the 5- or 6-membered heteroaryl contains one or two heteroatoms individually selected from N, O, or S, provided that no more than one is O or S; and wherein any of the phenyl, 5- or 6-membered heteroaryl, and C3-C6-cycloalkyl is unsubstituted or substituted by one or two substituents independently selected from: halogen, cyano, C1-C3-alkyl, C1-C2-haloalkyl, or C1-C3-alkoxy.

8. The compound having formula (I) according to claim 6, wherein, Z 1 It is selected from 2,4-difluorophenyl, 3,5-difluoro-2-pyridyl, 2-fluorophenyl, 4-fluorophenyl, or phenyl.

9. The compound having formula (I) according to any one of claims 1 to 8, wherein, The compound having formula (I) is a compound having formula (III). (III) Where R 1 R 2 R 3 R 4 R 5 R 6 and Z 1 It is as defined for compounds having formula (I) according to any one of claims 1 to 4, and 7 to 8. A is selected from A-1, A-2, A-3, A-4, A-5, A-6, A-7, or A-8: The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to say Z 1 The nitrogen atom of the group bond, and where R 7 R 8 and R 9 Independently selected from hydrogen, halogen, or trifluoromethyl; Q is selected from Q-1, Q-2, Q-3, Q-7, Q-8, Q-9, Q-10, Q-12, or Q-15; The dashed lines indicate bonds extending to the rest of the molecule; R 10a and R 10b Independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl; and R 11 It is hydrogen, methyl, or ethyl.

10. The compound having formula (I) according to claim 9, wherein, A is selected from A-1 or A-2. The dashed line indicates the bond to the C(=O) group, and the asterisk ( ) indicates having to say Z 1 The nitrogen atom in the group.

11. The compound having formula (I) according to claim 9 or 10, wherein, Q is selected from Q-1, Q-2, or Q-3; The dashed lines indicate bonds extending to the remainder of the molecule; and R 10a and R 10b It is independently selected from hydrogen, halogen, cyano, C1-C3-alkyl, C1-C3-alkoxy, or C3-C6-cycloalkyl.

12. An agricultural chemical composition comprising a fungicide effective amount of the compound having formula (I) according to any one of claims 1 to 11.

13. The agrochemical composition according to claim 12, further comprising at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

14. A method for controlling or preventing the infection of useful plants by plant pathogenic microorganisms, wherein a fungicide effective amount of a compound having formula (I) according to any one of claims 1 to 11, or a composition comprising a compound having formula (I), is applied to the plant, its parts or the site thereof.

15. Use of the compound according to any one of claims 1 to 11 as a fungicide.

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