Condensed bicyclic heteroaromatic compounds with pesticidal activity

Abstract

Compounds of formula I wherein the substituents are as defined in claim 1, and agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds can be used as insecticides.

Description

[0001] This invention relates to quinazoline compounds with pest-killing activity (particularly insecticidal activity), methods for their preparation, compositions comprising those compounds, and their use for controlling animal pests (including arthropods and particularly insects or representatives of mites).

[0002] WO 2017192385 describes certain heteroaryl-1,2,4-triazole and heteroaryl-tetraazole compounds for the control of ectoparasites in animals (such as mammals and non-mammals).

[0003] Novel quinazoline and quinoline compounds with harmful biological activity have been discovered.

[0004] Therefore, in a first aspect, the present invention relates to compounds having formula I.

[0005]

[0006] in:

[0007] A1, A2, and A3 are N or CR independently of each other. Y ;

[0008] A4 and A5 are either N or CR, independent of each other. Y ;

[0009] Q is

[0010] R1 is hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl. 1-C2 alkyl-, C3-C4 cycloalkyl where the C3-C4 cycloalkyl group is substituted by 1 or 2 halogen atoms, C1-C2 alkyl-, oxetane-3-yl-CH2-, C1-C6 alkyl carbonyl, C1-C6 alkoxy carbonyl, phenyloxy carbonyl, benzyloxy carbonyl, benzyl or benzyl substituted by 1 to 3 substituents independently selected from halogen, C1-C6 alkoxy and C1-C6 haloalkyl;

[0011] R 2a and R 2bEach is independently selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, NO2, SF5, CN, C(O)NH2, C(O)OH, C(S)NH2, C3-C6 cycloalkyl, and is selected by one to three independently selected from R. x The substituents are C3-C6 cycloalkyl, C3-C6 cycloalkyl carbonyl, phenyl, and are independently selected from R. x The substituents are phenyl groups, heteroaryl groups, and are independently selected from R. x The substituent is a heteroaryl group; OR6, piperidin-2-one-1-yl, and is independently selected from R x The substituents of piperidin-2-one-1-yl, pyridin-2-one-1-yl, are independently selected from R x The substituents are pyridin-2-one-1-yl, aziridine-1-yl, or substituted with one or two groups independently selected from R. x The substituents are aziridine-1-yl, pyrrolidine-1-yl, or are independently selected from R x The substituents are pyrrolidin-1-yl, C3-C6 cycloalkyl, C1-C4 alkyl, and are independently selected from R z The C3-C6 cycloalkyl group substituted with a C1-C4 alkyl group; the C3-C6 cycloalkyl group with a C1-C3 alkoxy group, and the C3-C6 cycloalkyl group being substituted with one or two independently selected from R x The substituents are C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, C1-C4 alkylthioalkyl, and are independently selected from R x The substituents of the C1-C4 alkylthioalkyl, C1-C4 alkylsulfonyl groups are one to three independently selected from R x The substituents are C1-C4 alkyl sulfonyl groups, C1-C4 alkyl sulfinyl groups, and groups independently selected from R x The C1-C4 alkyl sulfinyl group is substituted by the substituent;

[0012] R3 is a C1-C3 alkyl or a C1-C3 haloalkyl;

[0013] R4 is pyridine, pyrimidine, pyrazine, or pyridazine; or

[0014] R4 is a pyridine, pyrimidine, pyrazine, or pyridazine, each of which is independently substituted by one or two substituents independently selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)- and optionally a 5-membered heteroaryl ring substituted by one to three substituents independently selected from the following: halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy;

[0015] R 4a It is pyridine, pyrimidine, pyrazine, or pyridazine; or

[0016] R 4a It is pyridine, pyrimidine, pyrazine, or pyridazine, each of which is independently substituted by one to three independently selected from the following substituents: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, hydroxyl, cyano, and C1-C3 haloalkoxy; or

[0017] R 4a It is Y1, Y2, Y3, and Y4.

[0018]

[0019] Among them, R' 4a 、R' 4b 、 and R' 4c They are selected independently of each other and independently of Y1 to Y4 from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy;

[0020] R5 represents hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, C3-C4 alkoxy C(O)-, (C1-C3 alkoxy)2CH-, halogen, CN, NH2C(O), amino (i.e., NH2), (C1-C3 alkyl)amino, di(C1-C3 alkyl)amino, hydroxyl, C3-C4 halocycloalkyl, C3-C4 cyanocycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C4 haloalkylthioalkyl, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylthioalkyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C 3-alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)sulfonylamino, (C1-C3 alkyl)sulfonyl(C1-C3 alkyl)amino, (C1-C3 alkyl)NHC(O), (C1-C3 alkyl)2NC(O), (C1-C3 cycloalkyl)NHC(O), (C1-C3 cycloalkyl)(C1-C3 alkyl)NC(O), (C1-C3 alkyl)C(O)(C1-C3 alkyl)N, (C1-C3 alkyl)C(O)NH, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O), HC(O), diphenylmethyleneimine, C1-C3 haloalkoxy, phenyl, or a 5-membered heteroaromatic ring; or

[0021] R5 is a phenyl group, wherein the phenyl group is substituted by one to three substituents selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN, and hydroxyl; or

[0022] R5 is a 5-membered heteroaromatic ring, which is substituted by one to three substituents selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN and hydroxyl;

[0023] R 5a and R 5b They are independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy;

[0024] R6 is phenyl, benzyl, heteroaryl, or C3-C6 cycloalkyl; or

[0025] R6 is a phenyl, benzyl, heteroaryl, or C3-C6 cycloalkyl group, each of which is independently selected from one to three independently selected from R6. x Substituents of the substituents;

[0026] R x Independently selected from halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, NO2, SF5, CN, C(O)NH2, C(S)NH2, C1-C4 haloalkylthioalkyl, C1-C4 haloalkylsulfinyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylthioalkyl, C1-C4 alkylsulfinyl and C1-C4 alkylsulfonyl;

[0027] R Y Selected from hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN, and cyclopropyl; and

[0028] R Z It is selected from oxo groups, halogens, C1-C3 alkyl groups, C1-C3 haloalkyl groups, C1-C3 alkoxy groups, C1-C3 haloalkoxy groups and CN; or agriculturally chemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of compounds having Formula I.

[0029] Compounds of formula I having at least one basic center can form acid addition salts, for example, 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, such as 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). Compounds of Formula I having at least one acidic group can, for example, form salts with bases, such as mineral salts, like alkali metal or alkaline earth metal salts, such as sodium, potassium, or magnesium salts; or form salts with ammonia or organic amines (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).

[0030] In each case, the compound of formula I according to the invention is in a free form, an oxidized form such as an N-oxide, or a salt form (e.g., an agronomically usable salt form).

[0031] 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.

[0032] The compounds of formula I according to the present invention also include hydrates that may form during salt formation.

[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 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, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl.

[0034] 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., any one of the following: 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, 2,2,2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoroethyl Propyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 1-(fluoromethyl)-2-fluoroethyl, 1-(chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, or nonafluorobutyl. Accordingly, the term "C1-C2 fluoroalkyl" will refer to a C1-C2 alkyl group having 1, 2, 3, 4, or 5 fluorine atoms, such as any of the following: difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, or pentafluoroethyl.

[0035] 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 1 to n carbon atoms, which is attached via an oxygen atom, i.e., any of the following groups, for example: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy, or 1,1-dimethylethoxy. As used herein, the term "halogenated C1-C" is used in conjunction with "alkoxy". n "Alkoxy" refers to C1-C n Alkoxy groups, wherein one or more hydrogen atoms on an alkyl group are replaced by one or more halogen atoms of the same or different type—examples include trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 3,3,3-trifluoropropoxy, and 4-chlorobutoxy.

[0036] As used in this article, the term "C1-C" n "Cyanoalkyl" refers to a straight-chain or branched saturated C1-C alkyl group having 1 to n carbon atoms. n Alkyl groups (as described above), wherein one of the hydrogen atoms in these groups is replaced by a cyano group: for example, cyanomethyl, 2-cyanoethyl, 2-cyanopropyl, 3-cyanopropyl, 1-(cyanomethyl)-2-ethyl, 1-(methyl)-2-cyanoethyl, 4-cyanobutyl, etc.

[0037] As used in this article, the term "C3-C" n "Cycloalkyl" refers to 3- to n-membered cycloalkyl groups, such as cyclopropane, cyclobutane, cyclopentane, and cyclohexane.

[0038] As used in this article, the term "C3-C" n "Cycloalkyl carbonyl" refers to a 3-n-membered cycloalkyl group attached to a carbonyl (C=O) group, which is then attached to the remainder of the molecule. Similarly, as used herein, the term "C1-C" refers to a cycloalkyl group attached to a carbonyl (C=O) group. n Alkyl carbonyl, C1-C n "Alkoxycarbonyl", "phenyloxycarbonyl" and "benzyloxycarbonyl" refer to alkyl, alkoxy, phenyloxy and benzyloxy groups attached to a carbonyl (C=O) group, which is attached to the remainder of the molecule.

[0039] As used herein, the term “C3-C4 cycloalkyl-C1-C2 alkyl” refers to a 3- or 4-membered cycloalkyl group with a methylene or ethylene group attached to the remainder of the molecule. In this case, C3-C4 cycloalkyl-C1-C2 alkyl is substituted, and one or more substituents may be attached to the cycloalkyl and / or alkyl group.

[0040] As used herein, the term “C3-C6 cycloalkyl C1-C4 haloalkoxy” refers to a 3- to 6-membered cycloalkyl group attached to a 1- to 4-membered haloalkoxy group, which is attached to the remainder of the molecule.

[0041] As used herein, the term "aminocarbonyl C1-C" n "Alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a CONH2 group.

[0042] As used herein, the term "hydroxycarbonyl C1-C" n "Alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a COOH group.

[0043] As used in this article, the term "C1-C" n "alkyl-thioalkyl" refers to C1-C atoms linked by sulfur atoms. n Alkyl moiety. Similarly, as used herein, the term "C1-C" refers to the alkyl group. n "Halogenated alkylthio" or "C1-C" n "Halogenated alkyl thioalkyl" refers to C1-C atoms linked by sulfur atoms. n Haloalkyl moiety. Similarly, the term "C3-C" n "Cycloalkylthioalkyl" refers to a 3-n-membered cycloalkyl moiety linked by a sulfur atom.

[0044] As used in this article, the term "C1-C"n "alkyl sulfinyl" refers to a C1-C group connected by a sulfur atom in an S (=O) group. n Alkyl moiety. Similarly, as used herein, the term "C1-C" refers to the alkyl group. n "halogenated alkyl sulfinyl" or "C1-C" n "Haloalkylsulfinyl" refers to a C1-C group connected by a sulfur atom via an S (=O) group. n Haloalkyl moiety. Similarly, the term "C3-C" n "Cycloalkylsulfinyl" refers to a 3-n-membered cycloalkyl moiety connected by a sulfur atom in an S (=O) group.

[0045] As used in this article, the term "C1-C" n "alkylsulfonyl" refers to a C1-C group connected by a sulfur atom in an S(=O)2 group. n Alkyl moiety. Similarly, as used herein, the term "C1-C" refers to the alkyl group. n "halogenated alkyl sulfonyl" or "C1-C" n "Halogenated alkyl sulfonyl" refers to a C1-C group connected by a sulfur atom via an S(=O)2 group. n Haloalkyl moiety. Similarly, the term "C3-C" n "Cycloalkylsulfonyl" refers to a 3-n-membered cycloalkyl moiety connected by a sulfur atom of an S(=O)2 group.

[0046] As used herein, the term "trimethylsilane C1-C" n "Alkyl" refers to an alkyl group in which one of the hydrogen atoms in the group is replaced by a -Si(CH3)3 group.

[0047] As used in this article, the term "C2-C" n "Alkenyl" refers to a straight-chain or branched alkenyl chain having two to n carbon atoms and one or two double bonds, such as vinyl, prop-1-alkenyl, and but-2-alkenyl.

[0048] As used in this article, the term "C2-C" n "Haloalkenyl" refers to a C2-C group that is substituted by one or more halogen atoms that may be the same or different. n Alkenyl moiety.

[0049] As used in this article, the term "C2-C" n "Alynyl" refers to a straight or branched alkynyl chain with two to n carbon atoms and a triple bond, such as ethynyl, prop-2-alkynyl, and but-3-alkynyl.

[0050] As used in this article, the term "C2-C" n "Haloacetylenic" refers to a C2-C group that is substituted by one or more halogen atoms that may be the same or different. n Alkyne moiety.

[0051] Halogens, or "halogenated," are typically fluorine, chlorine, bromine, or iodine. This also applies accordingly to halogens combined with other meanings, such as alkyl halogens.

[0052] As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic ring having one to three heteroatoms independently selected from N, O, and S. Examples are the heteroaryls J-1 to J-35 shown in Scheme A below. Preferred heteroaryls are preferably pyridyl, pyrimidinyl, and pyrazolyl.

[0053] Option A: Heteroaryl J-1 to J-35:

[0054]

[0055] R4 and R 4a The pyridine, pyrimidine, pyrazine, and pyridazine groups (unsubstituted or substituted) are each attached to the remainder of the compound via carbon atoms on their respective rings.

[0056] As used herein, the term “control” refers to reducing the number of pests, eliminating pests, and / or preventing further pest damage, thereby reducing damage to plants or plant-derived products.

[0057] For example, in this article, in Q a The interlaced lines used in Y-1 indicate the connection / attachment points with the remainder of the compound.

[0058] As used herein, the term "pest" refers to insects and mollusks found 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 life cycle of the said pests.

[0059] 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.

[0060] 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.

[0061] As will be understood by those skilled in the art, compounds having Formula I contain a stereocenter, which is indicated by an asterisk in the following structures:

[0062]

[0063] Among them, R1, R 2a R 2b R3, Q, A1, A2, A3, A4, and A5 are as defined in the first aspect.

[0064] This invention considers both racemic mixtures and individual enantiomers. Compounds with preferred stereochemistry are listed below.

[0065]

[0066] The particularly preferred compounds of the present invention are compounds having the formula I'a:

[0067] Among them, R1, R 2a R 2b R3, Q, A1, A2, A3, A4, and A5 as defined in the first aspect, and stereoisomers, enantiomers, tautomers, and N-oxides of compounds having formula (I'a), and their agrochemically acceptable salts.

[0068] As used herein, the term “optionally substituted” means that the group referred to is either unsubstituted or substituted with a specified substituent, such as “C3-C4 cycloalkyl optionally substituted with one or two halogen atoms” meaning C3-C4 cycloalkyl, C3-C4 cycloalkyl substituted with one halogen atom, and C3-C4 cycloalkyl substituted with two halogen atoms.

[0069] Embodiments of the present invention are provided, as listed below.

[0070] In each embodiment of the invention

[0071] A. A1, A2, and A3 are N or CR independently of each other. Y The premise is that no more than two of the three are N; or

[0072] B. A1 and A3 are N and A2 is CR. Y ;or

[0073] C. A1, A2, and A3 are N or CH independently of each other; or

[0074] D. A1, A2, and A3 are independently N or CH, provided that no more than two of the three are N; or

[0075] E.A1 is N, and A2 and A3 are CH; or

[0076] F.A1 and A2 CH, and A3 is N; or

[0077] G.A1 and A3 are N, and A2 is CH; or

[0078] H.A1 and A3 are N, and A2 is CH.

[0079] In each embodiment of the invention

[0080] A.A4 is CR Y And A5 is N; or

[0081] B.A4 is CR Y And A5 is CH; or

[0082] C.A4 is CH, and A5 is N; or

[0083] D.A4 is N, and A5 is CH; or

[0084] Both E.A4 and A5 are CH.

[0085] In each embodiment of the invention

[0086] A. A1 is N, A2 and A3 are CH, and A4 and A5 are both CH; or

[0087] B. A1 and A2 are CH, A3 is N, and A4 and A5 are both CH.

[0088] C. A1 and A3 are N, A2 is CH, and A4 is CR. Y And A5 is CH; or

[0089] D. A1 and A3 are N, A2 is CH, and A4 is CH and A5 is N; or

[0090] E. A1 and A3 are N, A2 is CH, and A4 is N and A5 is CH; or

[0091] F. A1 and A3 are N, A2 is CH, and A4 is either N or CH and A5 is CH; or

[0092] G.A1 and A3 are N, A2 is CH, and A4 is CH and A5 is either N or CH; or

[0093] H.A1 and A3 are N, A2 is CH, and A4 and A5 are both N; or

[0094] I. A1 and A3 are N, A2 is CH, and A4 and A5 are both CH.

[0095] In embodiments of each aspect of the invention, R1 is

[0096] A. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonylC1-C6 alkyl, hydroxycarbonylC1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilaneC1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 ynyl, C2-C6 haloynyl, C3-C4 cycloalkylC1-C2 alkyl-, wherein the C3-C4 cycloalkyl group is substituted with 1 or 2 halogen atoms, C3-C4 cycloalkylC1-C2 alkyl-, oxetane-3-yl-CH2-, C1-C3 alkylcarbonyl, C1-C3 alkoxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, or benzyl; or

[0097] B. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl, or benzyl; or

[0098] C. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonylC1-C6 alkyl, hydroxycarbonylC1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkylC1-C2 alkyl-, benzyloxycarbonyl, or benzyl; or

[0099] D. Hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl-C1-C2 alkyl-, benzyloxycarbonyl, or benzyl; or

[0100] E. Hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl, C3-C4 cycloalkyl-C1-C2 alkyl-, benzyloxycarbonyl, or benzyl; or

[0101] F. Hydrogen, C1-C3 alkyl, C1-C3 cyanoalkyl, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C2-C4 haloalkynyl, C3-C4 cycloalkyl-C1-C2 alkyl-, benzyloxycarbonyl, or benzyl; or

[0102] G. hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl, or benzyl; or

[0103] H. hydrogen, methyl, ethyl, allyl, propargyl, or cyclopropyl-methyl; or

[0104] I. Hydrogen, methyl, propargyl, or cyclopropyl-methyl;

[0105] In embodiments of each aspect of the invention, R 2a yes

[0106] A. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkyl carbonyl, phenyl, heteroaryl selected from J-1 and J-35, each of the C3-C4 cycloalkyl, phenyl or heteroaryl groups being independently substituented by one to three R groups. x Substitution; OR6, piperidin-2-one-1-yl, pyridin-2-one-1-yl, optionally replaced by R x Substituted azacyclic butane-1-yl, pyrrolidine-1-yl, or those with one or two substituents R Z Substituted C3-C6 cycloalkyl C1-C4 alkyl, optionally R x The substituted C3-C6 cycloalkyl C1-C3 alkoxy, C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, optionally with one to three substituents R x Substituted C1-C4 alkylthioalkyl groups, optionally with one to three substituents R x The substituted C1-C4 alkyl sulfonyl group, or optionally with one to three substituents R x Substituted C1-C4 alkyl sulfinyl groups; or

[0107] B. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkyl carbonyl, phenyl, pyrazolyl, each of C3-C4 cycloalkyl, phenyl, and pyrazolyl is independently substituent for one to three R groups. x Substitution; OR6, piperidin-2-one-1-yl, pyridin-2-one-1-yl, optionally replaced by R xSubstituted azacyclic butane-1-yl, pyrrolidine-1-yl, optionally with one or two substituents R Z Substituted C3-C6 cycloalkyl C1-C4 alkyl, optionally R x The substituted C3-C6 cycloalkyl C1-C3 alkoxy, C1-C5 cyanoalkyl, C1-C5 cyanoalkoxy, optionally with one to three substituents R x Substituted C1-C4 alkylthioalkyl groups, optionally with one to three substituents R x The substituted C1-C4 alkyl sulfonyl group, or optionally with one to three substituents R x Substituted C1-C4 alkyl sulfinyl groups; or

[0108] C. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C6 cycloalkyl carbonyl, phenyl or pyrazolyl, each of C3-C4 cycloalkyl, phenyl, and pyrazolyl groups being independently substituted by one or two of the following substituents: R x OR6, optional R x Substituted azacyclobutane-1-yl, optionally with one or two substituents R Z Substituted C3-C6 cycloalkyl C1-C4 alkyl, optionally R x The substituted C3-C6 cycloalkyl C1-C3 alkoxy group, optionally with one to three substituents R x Substituted C1-C4 alkylthioalkyl groups, optionally with one to three substituents R x The substituted C1-C4 alkyl sulfonyl group, or optionally with one to three substituents R x Substituted C1-C4 alkyl sulfinyl groups; or

[0109] D. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, with one or two substituents R x Substituted C3-C4 cycloalkyl; C3-C6 cycloalkyl carbonyl, OR6, C3-C6 cycloalkyl C1-C4 alkyl, or R with one or two substituents. Z Substituted C3-C6 cycloalkyl, C1-C4 alkyl, C1-C4 alkylthioalkyl, or R-substituted with one to three substituents x Substituted C1-C4 alkylthioalkyl, C1-C4 alkylsulfonyl, or R with one to three substituents x Substituted C1-C4 alkylsulfonyl, C1-C4 alkylsulfinyl, or with one to three substituents R x Substituted C1-C4 alkyl sulfinyl groups; or

[0110] E. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C4 cycloalkyl, C3-C4 cycloalkyl substituted with one or two substituents independently selected from halogen, C1-C3 alkyl and C1-C3 haloalkyl, C3-C4 cycloalkyl carbonyl, C3-C4 cycloalkyl methyl, C3-C4 cycloalkyl methyl substituted with one or two substituents independently selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, C1-C2 alkylthioalkyl substituted with one or three halogens or C1-C2 alkylsulfonyl substituted with one or three halogens; or

[0111] F. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, cyclopropyl substituted with one or two substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropyl carbonyl, cyclopropyl methyl substituted with one or two substituents independently selected from oxo, halogen, and trifluoromethyl, or C1-C3 substituted with one or three halogens. 1- C2 alkyl thioalkyl or C2 substituted with one to three halogens 1- C2 alkylsulfonyl; or

[0112] G. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with one to three independently selected substituents chosen from C1-C3 alkyl, C1-C3 haloalkyl, cyano, and halogen, cyclopropylcarbonyl, C3-C6 cycloalkyl, C1-C4 alkyl, substituted with one to five independently selected substituents. C3-C6 cycloalkyl, C1-C4 alkyl, C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C3-C6 cycloalkylthioalkyl, C3-C6 cycloalkylsulfinyl, or C3-C6 cycloalkylsulfonyl; or

[0113] H. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with one or two substituents independently selected from C1-C3 haloalkyl, cyano, and halogen, C3-C4 cycloalkyl carbonyl, C3-C6 cycloalkyl C1-C4 alkyl, substituted with one to three independent substituents. The C3-C6 cycloalkyl, C1-C4 alkyl, C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C3-C6 cycloalkylthioalkyl, C3-C6 cycloalkylsulfinyl, or C3-C6 cycloalkylsulfonyl; or

[0114] I. Hydrogen, halogen, C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkoxy, C3-C6 cycloalkyl, C3-C6 cycloalkyl substituted with one or two substituents independently selected from C1-C3 haloalkyl, cyano, and halogen, C3-C4 cycloalkylcarbonyl, C3-C6 cycloalkylC1-C4 alkyl, C3-C6 cycloalkylC1-C4 alkyl substituted with one to three substituents independently selected from oxo, C1-C3 haloalkyl, cyano, and halogen, C1-C5 cyanoalkyl, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, C1-C4 alkylsulfinyl, C1-C4 haloalkylsulfinyl, C3-C6 cycloalkylthioalkyl, C3-C6 cycloalkylsulfinyl, or C3-C6 cycloalkylsulfonyl; or

[0115] J. Hydrogen, halogen, C3-C4 cycloalkyl, C3-C4 cycloalkyl carbonyl, optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, C1-C3 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkyl thioalkyl, C1-C3 haloalkyl sulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy or CN; or

[0116] K. Halogen, C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkylsulfonyl, or C1-C3 haloalkoxy; or

[0117] L. halogen, C1-C2 haloalkyl, C1-C2 haloalkylthioalkyl, C1-C2 haloalkylsulfonyl, or C1-C2 haloalkoxy; or

[0118] M. chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; or

[0119] N. Fluorine, chlorine, bromine, iodine, trifluoromethylthioalkyl, trifluoromethylsulfonyl, or trifluoromethyl; or

[0120] O. Trifluoromethyl, fluorine, bromine or chlorine.

[0121] In embodiments of each aspect of the invention, R 2b yes

[0122] A. Hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, cyclopropylcarbonyl, optionally substituents R Z C1-C3 alkoxy, C1-C3 haloalkoxy, or CN-substituted C3-C6 cycloalkyl or C1-C4 alkyl, optionally with one to three substituents R x The substituted C1-C4 alkylthioalkyl group, optionally with one to three substituents R x The substituted C1-C4 alkyl sulfonyl group, or optionally with one to three substituents R x Substituted C1-C4 alkyl sulfinyl groups; or

[0123] B. Hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, C1-C3 cycloalkyl-C1-C2 alkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN; or

[0124] C. Halogen, C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkylsulfonyl, or C1-C3 haloalkoxy; or

[0125] D. Halogen, C1-C2 haloalkyl, C1-C2 haloalkylthioalkyl, C1-C2 haloalkylsulfonyl, or C1-C2 haloalkoxy; or

[0126] E. Chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, trifluoromethylsulfonyl; or

[0127] F. Fluorine, chlorine, bromine, iodine, trifluoromethylthioalkyl, trifluoromethylsulfonyl, or trifluoromethyl; or

[0128] G. Trifluoromethyl, fluorine, bromine or chlorine.

[0129] In embodiments of each aspect of the invention, R3 is

[0130] A. C1-C3 alkyl or C1-C3 haloalkyl; or

[0131] B. Methyl or trifluoromethyl; or

[0132] C. Methyl.

[0133] In embodiments of each aspect of the invention, Q is

[0134] AQ a ;or

[0135] BQ b .

[0136] In embodiments of each aspect of the invention, Q a yes

[0137] A. Selected from Q a -1 to Q a -16; or

[0138] B. Selected from Q a -1、Q a -6、Q a -7、Q a -10, and Q a -15; or

[0139] CQ a -1 or Q a -15.

[0140]

[0141]

[0142] In embodiments of each aspect of the invention, Q b yes

[0143] A. Selected from Q b -1 to Q b -13; or

[0144] BQ b -1.

[0145]

[0146]

[0147] In embodiments of each aspect of the invention, R4 is

[0148] A. Pyridine or pyrimidine; wherein the pyridine or pyrimidine is optionally substituted independently of each other by one of the following substituents: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenoxy, C2-C6 haloalkynoxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C (S)-, (OH)N=C(NH2)-, J-13 (optionally substituted with 1 to 3 substituents independently selected from halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy), J-20 (optionally substituted with 1 to 3 substituents independently selected from halogens, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy), and 1H-tetrazol-5-yl; or

[0149] B. Pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by one of the following substituents: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenoxy, C2-C6 haloalkynoxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with C1-C3 haloalkyl, J-20 optionally substituted with C1-C3 haloalkyl, and 1H-tetrazol-5-yl; or

[0150] C. Pyridine, wherein the pyridine is optionally substituted with a substituent selected from one of the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenoxy, C2-C6 haloalkynoxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazol-5-yl; or

[0151] D. Pyrimidine; wherein the pyrimidine is optionally substituted with one of the following substituents: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenoxy, C2-C6 haloalkynoxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 (optionally substituted with trifluoromethyl), J-20 (optionally substituted with trifluoromethyl) and 1H-tetrazol-5-yl; or

[0152] E. Pyridine, pyrimidine, pyrazine, or pyridazine, wherein the pyridine, pyrimidine, pyrazine, or pyridazine is optionally substituted with a substituent selected from: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, F, Cl, Br, CN, and C1-C6 haloalkoxy; or

[0153] F. Pyridine, pyrimidine, pyrazine, or pyridazine, wherein the pyridine, pyrimidine, pyrazine, or pyridazine is optionally substituted by a substituent selected from: C1-C3 alkyl, C3-C4 cycloalkyl, F, Cl, Br, CN, and C1-C6 haloalkoxy; or

[0154] G. Pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted by a substituent selected from the following: cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy;

[0155] H. Pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted by a substituent selected from: cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy; or

[0156] I. 5-Cyclopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cyclopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, or pyrimidine; or

[0157] J. 5-Cyclopropylpyridin-2-yl, 5-Fluoropyridin-2-yl, 5-Chloropyridin-2-yl, 5-Bromopyridin-2-yl, 5-Difluoromethoxypyridin-2-yl, 5-Trifluoromethoxypyridin-2-yl, 5-Cyanopyridin-2-yl, 5-(2,2-Difluoroethoxy-pyridin-2-yl, 5-(2,2,2-trifluoroethoxy)-pyridin-2-yl, Pyridin-2-yl, 5-Cyclopropylpyrimidin-2-yl, 5-Fluoropyrimidin-2-yl, 5-Chloropyrimidin-2-yl, 5-Bromopyrimidin-2-yl, 5-Difluoromethoxypyrimidin-2-yl, 5-Trifluoromethoxypyrimidin-2-yl, 5-Cyanopyrimidin-2-yl, 5-(2,2-Difluoroethoxy)pyrimidin-2-yl, 5-(2,2,2-Trifluoroethoxy)pyrimidin-2-yl, or pyrimidin-2-yl; or

[0158] K. pyrimidin-2-yl, pyridin-2-yl, 5-bromopyrimidin-2-yl, 5-bromopyridin-2-yl, 5-cyanopyrimidin-2-yl, or 5-cyanopyridin-2-yl; or

[0159] L. pyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-bromopyridin-2-yl, or 5-cyanopyridin-2-yl.

[0160] In embodiments of each aspect of the invention, R 4a yes

[0161] A. Pyridine, pyrimidine, pyrazine, or pyridazine, wherein the pyridine, pyrimidine, pyrazine, or pyridazine is optionally and independently substituted by a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy and selected from Y-1 to Y-4; or

[0162] B. Pyridine, pyrimidine, pyrazine, or pyridazine, wherein the pyridine, pyrimidine, pyrazine, or pyridazine is optionally and independently substituted with one of the following substituents selected from F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy and selected from Y-1 to Y-4; or

[0163] C. Pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, or C1-C3 haloalkoxy and selected from Y-1 to Y-4; or

[0164] D. Pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy and selected from Y-1 to Y-4; or

[0165] E. 5-Cyclopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cyclopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, pyrimidine, or 1,2,3-triazole; or

[0166] F. 5-Cyclopropylpyridin-2-yl, 5-Fluoropyridin-2-yl, 5-Chloropyridin-2-yl, 5-Bromopyridin-2-yl, 5-Difluoromethoxypyridin-2-yl, 5-Trifluoromethoxypyridin-2-yl, 5-Cyanopyridin-2-yl, 5-(2,2-Difluoroethoxy)pyridin-2-yl, 5-(2,2,2-Trifluoroethoxy)pyridin-2-yl, Pyridin-2-yl, 5-Cyclopropylpyrimidine-2-yl - yl, 5-fluoropyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-bromopyrimidin-2-yl, 5-difluoromethoxypyrimidin-2-yl, 5-trifluoromethoxypyrimidin-2-yl, 5-cyanopyrimidin-2-yl, 5-(2,2-difluoroethoxy)pyrimidin-2-yl, 5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl, pyrimidin-2-yl, or 1,2,3-triazol-2-yl (or Y2); or

[0167] G. 1,2,3-triazol-2-yl (or Y2), pyrimidin-2-yl, or 5-cyanopyridin-2-yl.

[0168] In embodiments of each aspect of the invention, when Y-1 is selected as R 4a , R' 4a and R' 4c They are independent of each other

[0169] A. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; or

[0170] B. Selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy, and difluoromethoxy; or

[0171] C. All are hydrogen.

[0172] In each embodiment of the invention, when Y-2 is selected as R 4a ,

[0173] A.R' 4b and R' 4cIndependently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; or

[0174] B.R' 4b and R' 4c The groups are independently selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy, and difluoromethoxy; or

[0175] A.R' 4b and R' 4c All are hydrogen; or

[0176] B.R' 4b It is hydrogen and R' 4c It is cyclopropyl.

[0177] In embodiments of each aspect of the invention, when Y-3 is selected as R 4a , R' 4a and R' 4b They are independent of each other

[0178] A. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; or

[0179] B. Hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy, and difluoromethoxy; or

[0180] C. All are hydrogen.

[0181] In embodiments of each aspect of the invention, when Y-4 is selected as R' 4a ,

[0182] A.R' 4a 、R' 4b 、 and R' 4c Independently selected from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy; or

[0183] B.R' 4a 、R' 4b 、 and R' 4c The groups are independently selected from hydrogen, F, Cl, Br, CN, methyl, CF3, cyclopropyl, methoxy, and difluoromethoxy; or

[0184] C.R' 4a 、R' 4b 、 and R' 4c All are hydrogen; or

[0185] D.R' 4a and R' 4c It is hydrogen and R' 4b It's CN.

[0186] In embodiments of each aspect of the invention, R5 is

[0187] A. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, halogen, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O), HC(O), C1-C3 haloalkoxy, or a 5-membered heteroaromatic ring, wherein the 5-membered heteroaromatic ring is optionally substituted by one to three substituents selected from: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogen, CN, or hydroxyl; or

[0188] B. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, halogen, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O), HC(O) or C1-C3 haloalkoxy; or

[0189] C. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, halogen, Cl, Br, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), (C1-C3 alkoxy)C(O), or C1-C2 haloalkoxy; or

[0190] D. Hydrogen, C1-C3 alkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, C1-C3 haloalkoxy, halogen, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl, (C1-C3 alkyl)C(O), HC(O), or (C1-C3 alkoxy)C(O); or

[0191] E. Hydrogen, C1-C2 alkyl, C1-C2 alkoxy, C3-C4 cycloalkyl, C1-C2 haloalkoxy, halogen, C1-C2 alkoxy-C1-C2 alkyl, C1-C2 alkoxy-C1-C2 alkoxy-C1-C2 alkyl, (C1-C2 alkyl)C(O), HC(O), or (C1-C2 alkoxy)C(O); or

[0192] F. hydrogen, methyl, trifluoromethoxy, methoxy, cyclopropyl, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, difluoromethoxy, 2,2,2-trifluoroethyl, chlorine, bromine, methoxyethoxy, methyl carbonyl, or methoxycarbonyl; or

[0193] G. Hydrogen.

[0194] In embodiments of each aspect of the invention, R 5a yes

[0195] A. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy; or

[0196] B. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, or C1-C3 alkoxy; or

[0197] C. Hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, or C1-C3 alkoxy; or

[0198] D. Hydrogen, halogen, CN, C1-C3 alkyl or C1-C3 alkoxy; or

[0199] E. Hydrogen or halogen; or

[0200] F. Hydrogen.

[0201] In embodiments of each aspect of the invention, R 5b yes

[0202] A. Hydrogen, halogen, CN, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy; or

[0203] B. Hydrogen, halogen, or C1-C3 alkoxy group; or

[0204] C. Hydrogen.

[0205] In embodiments of each aspect of the invention, R6 is

[0206] A. Phenyl, benzyl, heteroaryl, or C3-C6 cycloalkyl, each of which is independently and optionally composed of a compound selected from R. x Substituents; or

[0207] B. Selected from R x The substituents are phenyl, benzyl, cyclopropyl or cyclopropyl.

[0208] In embodiments of each aspect of the invention, R x Selected independently

[0209] A. Halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN; or

[0210] BF, Cl, Br, OCF2H, OCH3, or CN.

[0211] In embodiments of each aspect of the invention, R Z Selected independently

[0212] A. Oxide group, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN; or

[0213] B. Oxide groups, F, Cl, Br, OCF2H, OCH3, or CN.

[0214] In embodiments of each aspect of the invention, R Y Selected independently

[0215] A. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, CN, and cyclopropyl; or

[0216] B. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, and cyclopropyl; or

[0217] C. Hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; or

[0218] D. Hydrogen, methyl, trifluoromethyl, and methoxy; or

[0219] E. Hydrogen.

[0220] Therefore, the present invention makes it possible to obtain substituents R1, R2 as defined above in all combinations / permutations. 2a R 2b Compounds of formula I, R3, Q, A1, A2, A3, A4, and A5. Thus, for example, it becomes possible to obtain compounds of formula I, wherein A1, A2, and A3 belong to the first aspect (i.e., A1, A2, and A3 are independently N or C). Y ; and R Y Belonging to Implementation Example D (i.e., R) Y Independently selected from hydrogen, methyl, trifluoromethyl, and methoxy); A4 and A5 belong to Example B (i.e., A4 is CR). Y And A5 is CH, where R Y Belongs to Implementation Example B (i.e., R) YHydrogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, halogen, or cyclopropyl); R1 is Example B (i.e., hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, aminocarbonyl C1-C6 alkyl, hydroxycarbonyl C1-C6 alkyl, C1-C6 nitroalkyl, trimethylsilane C1-C6 alkyl, C1-C3 alkoxy-C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C3-C4 cycloalkyl C1-C2 alkyl-, benzyloxycarbonyl, or benzyl); R 2a Example L (i.e., halogen, C1-C2 haloalkyl, C1-C2 haloalkylthioalkyl, C1-C2 haloalkylsulfonyl, or C1-C2 haloalkoxy); R 2b R3 is Example B (i.e., halogen, C1-C3 haloalkyl, or C1-C3 haloalkoxy); R3 is Example B (i.e., hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, C3-C4 cycloalkyl-C1-C2 alkyl optionally substituted with one or two substituents selected from the following: oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN); Q is Example A (i.e., Q is Q). a Q a It could be Example B (i.e., Q) a Selected from Q a -1、Q a -6、Q a -7、Q a -10, and Q a -15; and R 4 Example G (i.e., pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted by a substituent selected from the following: cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy).

[0221] In one embodiment, the compound having formula I is of formula Iaa, Iab, or Iac (the asterisk indicates a stereoisomer center), wherein R1, R... 2a R 2b R1 and R2 are as defined in the first aspect, and Q1 corresponds to Q as defined in the first aspect, each having a corresponding embodiment as described above.

[0222]

[0223] In one embodiment, compounds having the formulas Iaa, Iab, and Iac are also preferred to have compounds having the preferred stereochemistry shown in formula I'a. In a preferred embodiment, compounds having the formula Iab with the following stereochemistry are preferred:

[0224]

[0225] Among them, R1, R 2a R 2b R3, Q1 are stereoisomers, enantiomers, tautomers and N-oxides of compounds having the formula (I'ab), as defined in the first aspect, and agriculturally acceptable salts thereof.

[0226] In the embodiment, Q1 is

[0227] A. Selected from Q aa To Q ag and Q ba To Q bf ;or

[0228] B. Selected from Q aa To Q ag ;or

[0229] C. Selected from Q ba To Q bf ;or

[0230] D. Selected from Q aa Q ab Q ac Q af Q ag Q ba Q bb Q bc Q bd Q be and Q bf ;or

[0231] E. Selected from Q aa Q ab Q ac Q af Q af Q ba Q bb and Q bf ;or

[0232] F. Selected from Q aa Q ab Q ac Q af Q ba Q bb and Q bf .

[0233]

[0234]

[0235] In embodiments of each aspect of the invention, the compound having formula I has A1, A2, and A3 that are independently N or CR. Y (where R) Y (A1 is hydrogen, methyl, trifluoromethyl, and methoxy); A4 is N or CH, and A5 is CH; R1 is hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a The following are the possible meanings: hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, cyclopropyl substituted with one or two substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropyl carbonyl, cyclopropyl methyl substituted with one or two substituents independently selected from oxo, halogen, and trifluoromethyl, or C1-C3 substituted with one or three halogens. 1- C2 alkyl thioalkyl or C2 substituted with one to three halogens 1- C2 alkylsulfonyl group; R 2b The C3-C4 cycloalkyl group is hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, or CN; R3 is methyl; and Q is selected from Q. a -1 to Q a -16 and Q b -1 to Q b -13, where R4 (for Q) a -1 to Q a -16) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazole-5-yl; and R 4a (for Q) b -1 to Q b-13) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c The components are selected independently of each other and independently of Y-1 to Y-4 from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy.

[0236] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a The following are the possible meanings: hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, cyclopropyl, cyclopropyl substituted with one or two substituents independently selected from halogen, methyl, and trifluoromethyl, cyclopropyl carbonyl, cyclopropyl methyl substituted with one or two substituents independently selected from oxo, halogen, and trifluoromethyl, or C1-C3 substituted with one or three halogens. 1- C2 alkyl thioalkyl or C2 substituted with one to three halogens 1- C2 alkylsulfonyl group; R 2b The C3-C4 cycloalkyl group is hydrogen, halogen, C3-C4 cycloalkyl, cyclopropylcarbonyl, optionally substituted with one or two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, or CN; R3 is methyl; and Q is selected from Q. a -1 to Q a -16 and Q b -1 to Q b -13, where R4 (for Q) a -1 to Q a-16) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazole-5-yl; and R 4a (for Q) b -1 to Q b -13) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c The components are selected independently of each other and independently of Y-1 to Y-4 from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy.

[0237] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is a halogen, a C1-C3 haloalkyl, a C1-C3 haloalkylthioalkyl, a C1-C3 haloalkylsulfonyl, or a C1-C3 haloalkoxy; R 2b The halogen is a C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkylsulfonyl, or C1-C3 haloalkoxy; the methyl group is R3; and Q is selected from Q. a -1 to Q a -16 and Q b -1 to Q b -13, where R4 (for Q) a -1 to Q a-16) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazole-5-yl; and R 4a (for Q) b -1 to Q b -13) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c The components are selected independently of each other and independently of Y-1 to Y-4 from hydrogen, halogen, CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C4 cycloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy.

[0238] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is a halogen, a C1-C3 haloalkyl, a C1-C3 haloalkylthioalkyl, a C1-C3 haloalkylsulfonyl, or a C1-C3 haloalkoxy; R 2b The halogen is a C1-C3 haloalkyl, C1-C3 haloalkylthioalkyl, C1-C3 haloalkylsulfonyl, or C1-C3 haloalkoxy; the methyl group is R3; and Q is selected from Q. a -1 to Q a -16 and Q b -1 to Q b -13, where R4 (for Q) a -1 to Q a-16) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazole-5-yl; and R 4a (for Q) b -1 to Q b -13) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c (All are hydrogen).

[0239] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is a halogen, a C1-C2 haloalkyl, a C1-C2 haloalkylthioalkyl, a C1-C2 haloalkylsulfonyl, or a C1-C2 haloalkoxy; R 2b The methyl group is a halogen, a C1-C2 haloalkyl group, a C1-C2 haloalkylthioalkyl group, a C1-C2 haloalkylsulfonyl group, or a C1-C2 haloalkoxy group; the methyl group is R3; and Q is selected from Q. a -1 to Q a -16 and Q b -1 to Q b -13, where R4 (for Q) a -1 to Q a-16) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazole-5-yl; and R 4a (for Q) b -1 to Q b -13) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c (All are hydrogen).

[0240] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is a halogen, a C1-C2 haloalkyl, a C1-C2 haloalkylthioalkyl, a C1-C2 haloalkylsulfonyl, or a C1-C2 haloalkoxy; R 2b The methyl group is a halogen, a C1-C2 haloalkyl group, a C1-C2 haloalkylthioalkyl group, a C1-C2 haloalkylsulfonyl group, or a C1-C2 haloalkoxy group; the methyl group is R3; and Q is selected from Q. a -1 or Q b -1, where R4 (for Q) a -1) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazol-5-yl; and R 4a (for Q) b-1) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c (All are hydrogen).

[0241] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; R 2b The methyl group is chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; the methyl group is R3; and Q is selected from Q. a -1 or Q b -1, where R4 (for Q) a -1) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted independently of each other by a substituent selected from the following: C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C4 cycloalkyl, halogroup, hydroxyl, CN, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C2-C6 haloalkynyloxy, C3-C4 halocycloalkoxy, C3-C6 cycloalkylC1-C4 haloalkoxy, NH2C(O)-, NH2C(S)-, (OH)N=C(NH2)-, J-13 optionally substituted with a C1-C3 haloalkyl, J-20 optionally substituted with a C1-C3 haloalkyl, and 1H-tetrazol-5-yl; and R 4a (for Q) b -1) is pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from C1-C3 haloalkyl, C3-C4 cycloalkyl, halogen, cyano, C1-C3 haloalkoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c (All are hydrogen).

[0242] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; R 2b The methyl group is chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; the methyl group is R3; and Q is selected from Q.a -1 or Q b -1, where R4 (for Q) a -1) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted by a substituent selected from: cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy, and 2,2,2-trifluoroethoxy; and R 4a (for Q) b -1) is a pyridine or pyrimidine, wherein the pyridine or pyrimidine is optionally substituted with a substituent selected from cyclopropyl, F, Cl, Br, CN, trifluoromethoxy, difluoromethoxy, 2,2-difluoroethoxy and 2,2,2-trifluoroethoxy and selected from Y-1 to Y-4 (where R' 4a 、R' 4b 、 and R' 4c (All are hydrogen).

[0243] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iaa, Iab, or Iac, having R1 as hydrogen, methyl, propargyl, or cyclopropyl-methyl; R 2a It is chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; R 2b The methyl groups are chlorine, fluorine, bromine, iodine, difluoromethyl, trifluoromethyl, trifluoromethylthioalkyl, or trifluoromethylsulfonyl; the methyl group is R3; and Q is selected from Q. a -1 or Q b -1, where R4 (for Q) a -1) is 5-cyclopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cyclopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, or pyrimidine; and R 4a (for Q) b -1) is 5-cyclopropylpyridine, 5-fluoropyridine, 5-chloropyridine, 5-bromopyridine, 5-difluoromethoxypyridine, 5-trifluoromethoxypyridine, 5-cyanopyridine, 5-(2,2-difluoroethoxy)-pyridine, 5-(2,2,2-trifluoroethoxy)-pyridine, pyridine, 5-cyclopropylpyrimidine, 5-fluoropyrimidine, 5-chloropyrimidine, 5-bromopyrimidine, 5-difluoromethoxypyrimidine, 5-trifluoromethoxypyrimidine, 5-cyanopyrimidine, 5-(2,2-difluoroethoxy)-pyrimidine, 5-(2,2,2-trifluoroethoxy)-pyrimidine, pyrimidine, or 1,2,3-triazole.

[0244] In embodiments of each aspect of the invention, compounds having formula I are represented by formula Iab or I'ab, having R1 as in Example H (preferably hydrogen, methyl, propargyl, or cyclopropyl-methyl); R 2a Example N (preferably trifluoromethyl, fluorine, chlorine, or bromine); R 2b Example F (preferably fluorine, chloro, or trifluoromethyl); methyl group as R3; and Q1 selected from Q aa To Q ag and Q ba To Q bf (Preferred selection from Q) aa Q ab Q ac Q af Q ba Q bb and Q bf ).

[0245] In a second aspect, the invention makes it possible to obtain a composition comprising a compound having formula I as defined in the first aspect, one or more adjuvants and diluents, and optionally one or more other active ingredients.

[0246] In a third aspect, the invention enables the provision of a method for combating and controlling insects, mites, nematodes, or mollusks, the method comprising applying to the pest, the site of the pest, or plants susceptible to pest attack an effective amount of an insecticidal, acaricidal, nematodeic, or molluskic compound as defined in the first aspect or a composition as defined in the second aspect.

[0247] In a fourth aspect, the present invention provides a method for protecting plant propagation material from attacks by insects, mites, nematodes, or mollusks, the method comprising treating the propagation material or the site where the propagation material is grown with an effective amount of a compound having formula I as defined in the first aspect or a composition as defined in the second aspect.

[0248] In a fifth aspect, the invention enables the availability of a plant propagation material, such as a seed, which comprises a compound having Formula I as defined in the first aspect or a composition as defined in the second aspect, or is treated with the compound or the composition, or has the compound or the composition adhered thereto.

[0249] In another aspect, the present invention provides a method for controlling parasites internal or external to an animal in need, the method comprising administering an effective amount of the compound of the first aspect. The present invention further provides a method for controlling ectoparasites in an animal in need, the method comprising administering an effective amount of a compound having formula I as defined in the first aspect. The present invention further provides a method for preventing and / or treating diseases transmitted by ectoparasites, the method comprising administering an effective amount of a compound having formula I as defined in the first aspect to the animal in need.

[0250] Compounds having Formula I can be prepared by those skilled in the art according to known methods. More specifically, compounds having Formulas I and I'a and their intermediates can be prepared as described below in the schemes and examples. For clarity, certain stereocenters are not specified and are not intended to limit the teaching of these schemes in any way.

[0251] The method for preparing compounds having Formula I according to the present invention is carried out by methods known to those skilled in the art.

[0252] Compounds having formula I can be prepared, for example, as shown in Scheme 1.

[0253] Option 1:

[0254]

[0255] A compound having formula II (where X1 is a leaving group, such as a halogen or sulfonate, such as a chloride) reacts with a compound having formula III to give a compound having formula I, wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, and Q have the same meanings given above for compounds having formula I. The reaction can be carried out purely or in a solvent, preferably in a solvent such as an organic solvent like acetonitrile, with or without a catalyst (e.g., a metal catalyst, such as a palladium complex), and with or without the addition of a base, such as an inorganic base (e.g., potassium carbonate) or an organic base (e.g., like triethylamine). Compounds having formula II are known, or they can be prepared by methods known to those skilled in the art.

[0256] Option 2:

[0257]

[0258] Compounds having Formula III are prepared, for example, as shown in Scheme 2. Treatment of a compound having Formula V (where X2 is a leaving group, such as a halogen or sulfonate, such as a bromide) with an amine having Formula XIX yields a compound having Formula III. This reaction can be carried out purely, either with or without the addition of a base (such as an inorganic base, such as potassium carbonate) or an organic base (such as triethylamine)), or in a solvent, preferably an organic solvent such as acetonitrile. Alternatively, treatment of a compound having Formula VII with an amine having Formula XIX yields a compound having Formula III. This reaction is carried out in the presence of a reducing agent (such as hydrogen or a hydride, such as sodium borohydride), with or without a catalyst (such as a hydrogenation catalyst, such as palladium on carbon), with or without an acid (such as acetic acid or a Lewis acid, such as zinc bromide), in a solvent such as methanol, or in the absence of a solvent. The reaction can be carried out in a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Such methods for the alkylation and reductive alkylation of amines, and the range of conditions under which these methods are carried out, are well known to those skilled in the art. Amines having the formula XIX are known, or they can be prepared by methods known to those skilled in the art.

[0259] Option 3:

[0260]

[0261] Alternatively, compounds having formula I can be prepared, for example, as shown in Scheme 3. An amine having formula IV reacts with a compound having formula V (where X2 is a leaving group, such as a halogen or sulfonate, such as a bromide) to give a compound having formula I, wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, and Q have the same meaning as given above for compounds having formula I. This reaction can be carried out purely, either with or without the addition of a base (such as an inorganic base (e.g., potassium carbonate) or an organic base (e.g., triethylamine)), or in a solvent, preferably an organic solvent such as acetonitrile, within a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Such methods for the alkylation of amines and the range of conditions under which they are carried out are well known to those skilled in the art. Alternatively, an amine having formula IVa reacts with a compound having formula VII to give a compound having formula I, wherein R1 is H, and A1, A2, A3, A4, A5, R2a, R2b, R3, and Q have the same meaning as given above for compounds having formula I. The reaction is carried out in the presence of a reducing agent (e.g., hydrogen or a hydride such as sodium borohydride), with or without a catalyst (e.g., a hydrogenation catalyst such as palladium on carbon), with or without an acid (e.g., acetic acid or a Lewis acid such as zinc bromide), in a solvent such as methanol, or in the absence of a solvent. The reaction can be carried out in a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Such methods for the reductive alkylation of amines and the range of conditions under which they are carried out are well known to those skilled in the art.

[0262] Option 4:

[0263]

[0264] Compounds of formula V are prepared, for example, as shown in Scheme 4. Treatment of a compound of formula VIII with a halogenating agent, such as chlorine, bromine, or N-bromosuccinimide, yields a compound of formula V, wherein the leaving group Q is a halogen, such as a chloride or bromide. The reaction is carried out with or without a solvent, preferably in a solvent, with or without an additive, such as a free radical initiator, such as benzoyl peroxide or azoisobutyronitrile. The reaction can be carried out with or without exposure to visible or ultraviolet light, and the reaction can be carried out in a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Alternatively, a compound of formula VII can be treated with a reducing agent and then reacted with a sulfonyl chloride, such as methanesulfonyl chloride, to yield a compound of formula V, wherein the leaving group Q is a sulfonate, such as a methanesulfonate. The reaction can be carried out in a solvent or in the absence of a solvent, in the presence of a base (e.g., an inorganic base such as potassium carbonate, or an organic base such as an amine base such as trimethylamine) or in the absence of a base, and it can be carried out in a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Suitable reducing agents can be, for example, hydrogen, or hydrides (e.g., sodium borohydride), with or without a catalyst (e.g., a hydrogenation catalyst, such as palladium on carbon), with or without an acid (acetic acid or Lewis acid, such as zinc bromide), in a solvent (e.g., methanol) or in the absence of a solvent. The reaction can be carried out in a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Methods for the reduction of such halogenated and carbonyl compounds and the range of conditions under which they are carried out are well known to those skilled in the art. Amines having formula VII and compounds having formula VIII are known or can be prepared by methods known to those skilled in the art.

[0265] Option 5:

[0266]

[0267] Alternatively, compounds having formula I (where R1 is different from H) can be prepared, for example, as shown in Scheme 5. A compound having formula Ia can be reacted with a compound having formula VI (where X3 is a leaving group, such as a halogen or sulfonate, for example a chloride, bromide, iodide, or methanesulfonate) to give a compound having formula I, wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, and Q have the same meaning as given above for compounds having formula I. The reaction can be carried out purely, either with or without the addition of a base (such as an inorganic base (e.g., potassium carbonate) or an organic base (e.g., triethylamine)), or in a solvent, preferably an organic solvent such as acetonitrile, within a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Such methods for the alkylation of amines and the range of conditions under which they are carried out are well known to those skilled in the art.

[0268] Option 6:

[0269]

[0270] For example, compounds having formula Ib are shown in scheme 6. A compound having formula II (where X1 is a leaving group, such as a halogen or sulfonate, such as a chloride) reacts with a compound having formula IX to give a compound having formula X. This reaction can be carried out purely, either in a solvent, preferably in a solvent such as an organic solvent like acetonitrile or N,N-dimethylformamide, with or without a catalyst (e.g., a metal catalyst, such as a palladium complex), and with or without the addition of a base, such as an inorganic base (e.g., potassium carbonate) or an organic base (e.g., triethylamine). Compound X is then treated with a known compound XIII to give a compound having formula XI. The reaction can be carried out purely, either in the absence of a base or in a solvent, preferably an organic solvent such as dichloromethane, in the presence of a base (e.g., an inorganic base, such as potassium carbonate) or an organic base (e.g., triethylamine)) or in the presence of a base (e.g., potassium carbonate) or an organic base such as dichloromethane), between -100°C and +300°C, preferably between ambient temperature and 100°C or between ambient temperature and 50°C. Further reaction of compound XI with hydrazine XII yields a compound of formula Ib, wherein A1, A2, A3, A4, A5, R2a, R2b, R3, and R4 have the same meanings given above for compounds of formula I. The reaction can be carried out purely, either in the presence of a base (e.g., an inorganic base, such as potassium carbonate, or an organic solvent such as dioxane or acetic acid, or a mixture of dioxane and acetic acid), in the presence of a base (e.g., an inorganic base, such as potassium carbonate, or an organic solvent such as dichloromethane) or acetic acid. Within this transformation sequence, intermediate compounds having formulas X and XI can be used as crude products in subsequent steps, or they can be purified, for example by chromatography, and used in purified form for the next transformation.

[0271] Option 7:

[0272]

[0273] For example, compounds having formula Ic are shown in scheme 7. An amine having formula XIX reacts with a compound having formula XVII to give a compound having formula XVI. This reaction is carried out in the presence of a reducing agent (e.g., hydrogen or a hydride such as sodium borohydride), with or without a catalyst (e.g., a hydrogenation catalyst such as palladium on carbon), with or without an acid (e.g., acetic acid or a Lewis acid such as zinc bromide), in a solvent such as methanol, or in the absence of a solvent. The reaction can be carried out in a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. Such methods for the reductive alkylation of amines and the range of conditions under which these methods are carried out are well known to those skilled in the art. The intermediate having formula XVI then reacts with a compound having formula II to give a compound having formula XIV. The reaction can be carried out in a pure state or in a solvent, preferably in an organic solvent such as acetonitrile, with or without a catalyst (e.g., a metal catalyst, such as a palladium complex) and with or without the addition of a base, such as an inorganic base (e.g., potassium carbonate) or an organic base (e.g., triethylamine). Subsequently, the intermediate having formula XIV reacts with a compound having formula XV to give a compound having formula Ic, wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3, and R4 have the same meaning as the compounds having formula I described above, and M1 in R4-M1 is a metal, such as lithium, or -MgCl, or -ZnBr, or -B(OH)2; or R4-M1 represents a borate ester, such as pinacol ester of borate, or a tin alkane such as R4-Sn(n-Bu)3. Such transformations are known to those skilled in the art, and are respectively Suzuki-, Kumada-, Negishi-, or Stille- coupling reactions. These reactions are carried out in the presence of a catalyst (such as a metal catalyst, e.g., palladium catalyst) and a ligand (e.g., phosphine ligands, N-heterocyclic carbene (NHC) ligands, or phosphite ligands) within a temperature range of -100°C to +300°C, preferably between ambient temperature and 200°C. The reaction can be carried out with or without an additional metal catalyst, such as a copper salt (e.g., CuI). The reaction is carried out with or without a base, which can be an inorganic base, such as potassium carbonate or sodium hydroxide, or cesium carbonate, or an organic base, such as an amine base, e.g., triethylamine. The reaction is carried out with or without a solvent, preferably in a solvent. When heating the reaction mixture, the reaction can be carried out under microwave irradiation or with conventional heating, such as heating the reaction vessel in an oil bath. Alternatively, compound XVII can be reacted with a compound having formula XV to give intermediate XVIII.The reaction is carried out under essentially the same conditions as described for the conversion of intermediate XIV to a compound having formula Ic. Subsequently, intermediate XVIII reacts with amine IV to give a compound having formula Ic, wherein R1 is hydrogen and A1, A2, A3, A4, A5, R2a, R2b, R3, and R4 have the same meaning as the compounds having formula I described above. This reaction, in the presence of a reducing agent, is carried out under essentially the same conditions as described for the conversion of compound XVII to intermediate XVI. Alternatively, the intermediate compound having formula XVIII can be reacted with an amine having formula XIX to give an intermediate having formula IIIa. This reaction, in the presence of a reducing agent, is carried out under essentially the same conditions as described for the conversion of compound XVII to intermediate XVI. Subsequently, the intermediate having formula IIIa reacts with a compound having formula II to give a compound having formula Ic, wherein A1, A2, A3, A4, A5, R2a, R2b, R1, R3, and R4 have the same meaning as the compounds having formula I described above. The reaction is carried out under essentially the same conditions as the conversion of intermediate XVI to intermediate XIV described above. In these different multi-step sequences, intermediate compounds having formulas XIV, XVI, XVIII, and IIIa can be used as crude products of the corresponding subsequent steps, or they can be purified, for example by chromatography, and used in purified form for the next conversion. Compounds having formula XVII are known, or can be prepared by methods known to those skilled in the art.

[0274] For example, compounds having formula Id can be prepared by:

[0275]

[0276] Amines having formula IIIb

[0277]

[0278] Wherein R1, R3, R4a, R5a, and R5b are as described in Formula I, and are compounded with compounds having Formula II.

[0279]

[0280] Wherein A1, A2, A3, A4, A5, R2a, and R2b are as described in Formula I and X1 is a leaving group (such as a halogen or sulfonate, for example, a chloride) that undergoes the reaction.

[0281] The chemical process is described in more detail in Scheme 8.

[0282] Option 8:

[0283]

[0284] A compound having formula II (where X1 is a leaving group, such as a halogen or sulfonate, such as a chloride) reacts with a compound having formula IIIb to give a compound having formula Id, wherein A1, A2, A3, A4, A5, R1, R2a, R2b, R3, R4a, R5a, and R5b have the same meaning as given above for compounds having formula I. This reaction can be carried out purely or in a solvent, preferably in a solvent such as an organic solvent like acetonitrile, with or without a catalyst (e.g., a metal catalyst, such as a palladium complex), and with or without the addition of a base, such as an inorganic base (e.g., potassium carbonate) or an organic base (e.g., triethylamine).

[0285] The formation of compounds having formula IIIb is outlined in Scheme 9. Compounds having formula IIIb can be prepared, for example, in the presence of NaBH(OAc)3 or NaBH3CN, in a suitable solvent, preferably acetic acid, at room temperature, similar to WO 2002 / 088073, page 35, by treating compounds having formula XX (where R1 is as defined in formula I) with compounds having formula XX (where R3, R...). 4a R 5a and R 5b (As described in Formula I). ​​Alternatively, another reagent system for reductive amination uses a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0286] Amines having formula IIIc can be obtained by biocatalytic deracemization of amines having formula IIId. This can be achieved, for example, using a final immobilized form (e.g. Lipases of type 435, such as Candida antarcticis lipase B or Pseudomonas fluorescens lipase, are carried out in the presence of an acyl donor (e.g., ethyl methoxyethyl ester or vinyl acetate) in a suitable solvent (e.g., acetonitrile or methyl tert-butyl ether) at temperatures between 20°C and 100°C. Such methods are described, for example, in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The expected stereochemical results of such deracetamping of the enzyme are known to those skilled in the art and documented in the literature, for example in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc. 2015, 137, 3996-4009.

[0287] Option 9:

[0288]

[0289] In an alternative approach, compounds having formula IIIc can be synthesized as described in Scheme 10, from compounds having formula XXII (where R3, R... 4a R 5a and R 5b (As described in Formula I) to obtain:

[0290] Option 10:

[0291]

[0292] Amines having formula IIIc can be produced from intermediates having formula XXII (where R3, R...). 4a R 5a and R 5b This intermediate is obtained as described in Formula I and Z3 is NPhth or NBoc2. Such intermediates can be obtained from alcohols having Formula XXI via a mitsunobu reaction, which involves treating the alcohol having Formula XXI with diisopropyl azodicarbonate in the presence of a phosphine (such as triphenylphosphine or tributylphosphine) and an amine (such as phthalimide or bis(tert-butyloxycarbonyl)amine). The mitsunobu reaction is known to those skilled in the art for inverting stereocenters, as in, for example, Chem. Rev. [Chemical Review] 2009, 109, 2551-2651. The amine having Formula XXII can then be converted to an amine having Formula IIIc by treatment with hydrazine (if Z3 = NPhth) or with an acid, such as trifluoroacetic acid (if Z3 = NBoc2).

[0293] Alternatively, amines having formula IIIc can be reduced to azides having formula XXIII (where R3, R...) by treatment with triphenylphosphine and water (Staudinger reaction) or, for example, by hydrogenation using a palladium catalyst in the presence of hydrogen. 4a R 5a and R 5b (As described in Formula I). ​​Azides having Formula XXIII can be obtained by treating an alcohol having Formula XXI (wherein R3, R...) in a solvent (such as toluene or THF) in the presence of a base (such as DBU) with an azidizing agent (such as diphenylphosphohydrazide). 4a R 5a and R 5b(As described in Formula I). ​​Such methods are known to those skilled in the art for performing stereocenter flipping and are described in the literature, for example, Adv. Synth. Catal. [Advanced Synthesis and Catalysis] 2018, 360, 2157–2165.

[0294] Alcohols having formula XXI can be reacted with ketones having formula XXIV (where R3, R... 4a R 5a , and R 5b Enantioselective reduction (as described in Formula I) can be performed to obtain the product. Such reductions can be carried out in the presence of a hydrogen donor system (e.g., HCOOH / Et3N or HCO2NH4) using a catalyst (e.g., ruthenium or rhodium catalysts with chiral ligands such as RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF4[(R,R)-TsDPEN] (p-cymene)). Such methods are described in the literature, for example in J. Org. Chem. 2017, 82, 5607.

[0295] Alternatively, compounds having formula IIIc can also be prepared as outlined in scheme 11.

[0296] Option 11:

[0297]

[0298] Amines having formula IIIc can be reacted, for example, with acids such as trifluoroacetic acid or hydrochloric acid with amines having formula XXV (where R3, R... 4a R 5a and R 5b Amines having formula XXV can be prepared by deprotection of a diketone having formula XXVI (where R3 and R...). 4a (as described in Formula I) condenses a diamine having Formula XXVII (where R) 5a and R 5b It is obtained as described in Formula I. This condensation can be carried out in the presence of a suitable solvent such as ethanol or isopropanol, or in the presence of an oxidizing agent such as air or DDQ. Diketones having Formula XXVI can be formed by oxidizing hydroxyketones having Formula XXVII, wherein R3 and R... 4aAs described in Formula I. This oxidation may include, for example, SO3-pyridine in the presence of DMSO and a base such as triethylamine, or alternatively, sodium hypochlorite in the presence of a catalyst such as TEMPO / Bu4NHSO4. Examples of such oxidations can be found in the literature, for example in Synlett, 2014, 25, 596 or J. Am. Chem. Soc., 1990, 112, 5290-5313. Hydroxyketones having Formula XXVII can be oxidized by aldehydes having Formula XXIX (where R... 4a The benzoin condensation is synthesized by cross-benzoin condensation between an aldehyde having formula I and an aldehyde having formula XXVIII (wherein R3 is as described in formula I). ​​Aldehydes having formula XXVIII are commercially available in chiral forms, such as, for example, Boc-L-propanal (CAS 79069-50-4) or N-[(1S)-1-(cyclopropylmethyl)-2-oxo-ethyl] tert-butyl carbamate (CAS 881902-36-9). The cross-benzoin condensation is carried out in a conventional manner in the presence of a base (such as potassium tert-butoxide or isopropyl diethylamine), in a suitable solvent (such as DCM or THF), at a temperature between -20°C and the boiling point of the solvent, using an organic catalyst (such as a triazolium salt or thiazolylium salt). Examples of catalysts used for such conversions have been described in the literature, such as J. Am. Chem. Soc. 2014, 136, 7539-7542 or Org. Lett. 2016, 18, 4518-4521.

[0299] Option 12:

[0300]

[0301] As shown in Scheme 12, compounds having formula Id can alternatively be prepared by: making compounds having formula XXX (wherein A1, A2, A3, A4, A5, R1, R...) 2a R 2b R3, R 5a and R 5b It is defined in Equation I, and X 07 The leaving group (such as, for example, chlorine, bromine, iodine) reacts with compounds having formula XXXI (Styler reaction) or compounds having formula XXXII (Suzuki-Miyaura reaction) in the presence of a palladium catalyst, as described in detail in Scheme 7.

[0302] Compounds having formula XXX can be produced by amines having formula XXXIII and compounds having formula II (where A1, A2, A3, A4, A5, R...). 2a R 2bX1 and R1 are prepared by coupling under the conditions described in detail in Scheme 1 (as described in Scheme 1). Under the same conditions, if R1 = H, a compound having formula XXX can be obtained directly from a compound having formula XXXIV.

[0303] Compounds having formula XXXIII can be prepared, for example, by treating compounds having formula XXXIV with compounds having formula XXXV (where R1 is as defined in formula I) in the presence of NaBH(OAc)3 or NaBH3CN, in a suitable solvent, preferably acetic acid, at room temperature, similar to WO 2002 / 088073, page 35. Alternatively, another reagent system for reductive amination uses a combination of Ti(i-OiPr)4 and NaBH4 (see Synthesis 2003(14), 2206).

[0304] Amines having the formula XXXIV can be prepared by a deracemification procedure, which involves, for example, the selective acylation of an enantiomer. Such an example is described in more detail in Scheme 13.

[0305] Option 13:

[0306]

[0307] Amines having formula XXXIV can be racemiced by biocatalysis to produce amines having formula XXXIVa (where R3, R... 5a , and R 5b It is as described in Equation 1 and X 07 This can be obtained by removing a leaving group such as bromine, chlorine, or iodine. This can be achieved, for example, by using a final immobilized form (e.g., Lipases of type 435, such as Candida antarcticis lipase B or Pseudomonas fluorescens lipase, are carried out in the presence of an acyl donor (e.g., ethyl methoxyethyl ester or vinyl acetate) in a suitable solvent (e.g., acetonitrile or methyl tert-butyl ether) at temperatures between 20°C and 100°C. Such methods are described, for example, in J. Org. Chem. 2007, 72, 6918-6923 or Adv. Synth. Catal. 2007, 349, 1481-1488. The expected stereochemical results of such deracetamping of the enzyme are known to those skilled in the art and documented in the literature, for example in J. Org. Chem. 1991, 56, 2656-2665 or J. Am. Chem. Soc. 2015, 137, 3996-4009.

[0308] Alternatively, the resolution of amines having formula XXXIVa to give amines having formula XXXIV can be achieved using chiral auxiliaries, as described in Scheme 14.

[0309] Option 14:

[0310]

[0311] Amines having formula XXXIV can be obtained from intermediates having formula XXXVII (where R3, R...) by treatment with an acid (such as HCl) or a base (such as NaOH). 5a , and R 5b As described in compounds having Formula 1, X 07 It is a leaving group such as bromine, chlorine or iodine and X 12 * is a chiral auxiliary agent. Chiral auxiliaries having formula LII are, for example, mandelic acid or (1R)-methylchloroformate. An intermediate having formula XXXVII can be formed by coupling a chiral auxiliary having formula XXXVI (where X0 is a leaving group, such as chlorine) with an amine having formula XXXIVa, according to the conditions detailed in Scheme 1. Examples of such deracemification methods are reported in the literature, for example in J. Org. Chem. [Journal of Organic Chemistry] 2007, 72, 485-493.

[0312] Alternatively, amines having the formula XXXIV can be formed as described in Scheme 15.

[0313] Option 15:

[0314]

[0315] Alternatively, amines having formula XXXIV can be derived from intermediates having formula XXIIa (where R3, R...). 5a , and R 5b As described in Formula I, X 07 It is obtained by removing a leaving group, such as a halogen or sulfonate, such as a bromide, and Z3 is NPhth or NBoc2). Such intermediates can be obtained from alcohols having the formula XXIa (where R3, R... 5a , and R 5b It is as described in Equation I and X 07The amine (leaving group) is obtained via a photoelongation reaction involving treatment of an alcohol having the formula XXIa with diisopropyl azodicarbonate in the presence of a phosphine (such as triphenylphosphine or tributylphosphine) and an amine (such as phthalimide or bis(tert-butyloxycarbonyl)amine). Photoelongation reactions are known to those skilled in the art for inverting stereocenters, as described, for example, in Chem. Rev. [Chemical Review] 2009, 109, 2551-2651. The amine having the formula LIII can then be converted to an amine having the formula IId by treatment with hydrazine (if Z3 = NPhth) or with TFA (if Z3 = NBoc2).

[0316] Alternatively, amines having formula XXXIV can be reduced to azides having formula XXIIIa (where R3, R4, R5) by treatment with triphenylphosphine and water (Staudinger reaction) or, for example, by hydrogenation using a palladium catalyst in the presence of hydrogen. 5a , and R 5b It is as described in Equation I and X 07 The leaving group (e.g., halogen or sulfonate, such as bromide) is required. Azides having formula XXIIIa can be obtained by treating alcohols having formula XXIa in a solvent (e.g., toluene or THF) in the presence of a base (e.g., DBU) with an azidizing agent (e.g., diphenylphosphohydrazide). Such methods are known to those skilled in the art for inverting stereocenters and are described in the literature, for example, Adv. Synth. Catal. [Advanced Synthesis and Catalysis] 2018, 360, 2157–2165.

[0317] Alcohols having formula XXIa can be expressed by reacting ketones having formula XXIVa (where R3, R... 5a , and R 5b It is as described in Equation I and X 07 This is obtained by enantioselective reduction of the leaving group (e.g., halogen or sulfonate). Such reductions can be carried out in the presence of a hydrogen donor system (e.g., HCOOH / Et3N or HCO2NH4) using a catalyst (e.g., ruthenium or rhodium catalysts with chiral ligands such as RuCl[(R,R)-TsDPEN] (mesitylene) or RuBF4[(R,R)-TsDPEN] (p-cymene)). Such methods are described in the literature, for example in J. Org. Chem. 2017, 82, 5607.

[0318] Compounds having formula II:

[0319]

[0320] Where X1 is a leaving group, such as a halogen or sulfonate, such as chlorine, and can be prepared as shown in Schemes 16-18.

[0321] Option 16:

[0322]

[0323] Compounds having formula IIa can be prepared according to scheme 16, wherein R2a, R2b, A4, and A5 are as described in formula I. Compounds having formula XLII are known or can be prepared by methods known to those skilled in the art. For example, as described in J. Org. Chem. [Journal of Organic Chemistry] 2018, 83, 930, compounds having formula XL are reacted with an electrophilic iodinating agent (e.g., N-iodosuccinimide) in a solvent (e.g., hexafluoroisopropanol) to obtain compounds having formula XLI. The compound having formula XLI is cyanided with copper cyanide (I) in a solvent such as DMF at a temperature such as 100°C to provide compounds having formula XLII (a process similar to WO2005 / 100298, page 44). The compound having formula XLII is treated with formic acid and sulfuric acid at a temperature between 80°C and 100°C to provide compounds having formula XLIII (a method similar to WO2018 / 206539, page 80). Subsequently, according to methods known to those skilled in the art, such as in the presence of catalytic N,N-dimethylformamide, under reflux, thionyl chloride is used to convert the compound having formula IIa, similar to WO2015 / 54572, page 263.

[0324] Option 17:

[0325]

[0326] Compounds having formula IIb can be prepared according to reaction scheme 17, wherein R2a, R2b, A4, and A5 are as described in formula I. The compound having formula XLII prepared as in scheme 16 is reacted with a chlorosulfonyl isocyanate, and then further reacted with water under reflux, as described in Synth. Commun. 1988, 18, 525, to provide an intermediate having formula XLIV. The intermediate having formula XLIV is then converted to a compound having formula IIa using a chlorinating agent, such as POCl3, optionally in the presence of a base such as N,N-diisopropylethylamine. These chlorination methods are well known to those skilled in the art.

[0327] Option 18:

[0328]

[0329] Compounds having formula IIc can be prepared according to reaction scheme 18, wherein R2a, R2b, A4, and A5 are as described in formula I, similar to the procedure in ChemCatChem [Chemical Catalysis] 2017, 10, 965. Meldrum acid is converted to compound XLV by reflux in trimethyl orthoformate, and further converted to compound XLVI by addition of aniline having formula XL in the same vessel. Compound XLVI is refluxed in diphenyl ether to obtain 4-hydroxyquinoline having formula XLVII. Compound XLVII is then chlorinated using a chlorinating agent well known to those skilled in the art, such as POCl3, to obtain compound IIc.

[0330] For example, compounds having formula IVc

[0331]

[0332] It can be prepared as shown in Scheme 19.

[0333] Option 19:

[0334]

[0335] Compounds having formula IVc can be prepared according to reaction scheme 20, wherein Z is H, C1-C3 alkyl, cyclopropyl, CF3, R2a, R2b, A4, and A5 as described in formula I. Compounds having formula XLII prepared as in scheme 16 are reacted in the presence of compounds having formula XLVIII at elevated temperatures, for example, 180 °C, as described, for example, in Eur. J. Med. Chem. 2017, 141, 446, to provide amines of formula IVc.

[0336] Alternatively, compounds having the formula Iab can be prepared, for example, as shown in Scheme 20.

[0337] Option 20:

[0338]

[0339] Compounds having formula Iab can be prepared according to scheme 21, wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I, similar to the procedure in WO2010 / 093419, page 225. Compounds having formula XLII prepared according to scheme 16 are treated with N,N-dimethylformamide dimethylacetal at an elevated temperature, preferably 90°C, to provide a formamidinium product of formula XLVIII. In a suitable solvent, preferably acetic acid, at an elevated temperature, preferably 120°C, it is reacted with an amine having formula III to provide a compound having formula Iab.

[0340] For example, compounds with the formula If

[0341]

[0342] It can be prepared as shown in Scheme 21.

[0343] Option 21:

[0344]

[0345] Compounds having the formula If can be prepared according to Scheme 21, wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in Formula I. Using the procedure shown in Scheme 1, the compound having the formula IIb prepared in Scheme 17 is reacted with an amine having the formula III to provide a compound having the formula Ie. As described in Heterocycles 1996, 43, 2607, the compound having the formula Ie is treated under acidic conditions, preferably with acetic acid, at an elevated temperature, preferably between 70°C and 80°C, to provide an intermediate having the formula LI. As is well known to those skilled in the art, compounds having the formula LI can be methylated using an electrophilic methyl source, such as dimethyl sulfate or methyl iodide, in the presence of a base (e.g., potassium carbonate or sodium hydride) to obtain compounds having the formula If.

[0346] For example, compounds having the formula Ig

[0347]

[0348] It can be prepared as shown in Scheme 22.

[0349] Option 22:

[0350]

[0351] Compounds having formula Ig can be prepared according to scheme 22, wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I. As described in J. Org. Chem. 1990, 55, 2543, the compound having formula XLII prepared in scheme 16 is treated with a diazotizing agent, preferably isoamyl nitrite, in diiodomethane solvent at an elevated temperature, preferably 80°C, to provide an intermediate having formula LX. The compound having formula LX is reduced in a solvent such as toluene in the presence of a selective reducing agent such as diisobutylaluminum hydrogenation (DIBALH) at a low temperature, preferably -78°C, to give a compound having formula LXI. Subsequently, in the presence of a suitable palladium and copper catalyst, preferably palladium bis(triphenylphosphine)chloride and copper iodide (I), in a solvent such as triethylamine, it is subjected to a sonogashira coupling with trimethylsilylacetylene to give a compound having formula LXII. Cyclation with ammonia in methanol yields compounds having the formula LXIII. The procedure is similar to those described, for example, in Eur. J. Med. Chem. [European Journal of Medicinal Chemistry] 2016, 118, 170. Treatment of compounds having the formula LXIII in a solvent (preferably dichloromethane) with an oxidizing agent such as 3-chloro-phenylcarbazoic acid or hydrogen peroxide yields N-oxides having the formula LXIV. Such oxidations are well known to those skilled in the art. Compounds having the formula LXIV are further oxidized in a suitable activator (e.g., bromotripyrrolidinylphosphonium hexafluorophosphate). In the presence of a base (e.g., N,N-diisopropylethylamine), it may be coupled with an amine having formula III, similar to the method described in WO2016 / 123627, page 87, to give a compound having formula Ig.

[0352] For example, compounds having formula IId,

[0353]

[0354] Where X1 is a leaving group, such as a halogen or sulfonate, such as chlorine, which can be prepared as shown in Scheme 23.

[0355] Option 23:

[0356]

[0357] Compounds having formula IId can be prepared according to scheme 23, wherein R2a, R2b, A4, and A5 are as described in formula I. As described in EP1782811, page 57, the compound having formula XLI prepared in scheme 16 is treated at elevated temperatures, preferably 105°C, with a palladium catalyst, preferably Pd(PPh3)4, and tributyl(1-ethoxyvinyl)tin, to provide an intermediate having formula LXV. Similar to Bioorg. Med. Chem. Lett., 25, 919, the compound having formula LXV is treated with an aqueous sodium nitrite solution at low temperatures, preferably from 0°C to 5°C, in the presence of an acid such as hydrochloric acid or a sulfuric acid / acetic acid mixture, to give a compound having formula LXVI. The compound having formula IId is then obtained by chlorinating the compound having formula LXVI, optionally in the presence of an amine base such as N,N-diisopropylethylamine, using a chlorinating agent well known to those skilled in the art, such as POCl3.

[0358] For example, compounds having formula IIe,

[0359]

[0360] Where X1 is a leaving group, such as a halogen or sulfonate, such as chlorine, which can be prepared as shown in Scheme 24.

[0361] Option 24:

[0362]

[0363] Compounds having formula IIe can be prepared according to scheme 24, wherein R2a, R2b, A4, and A5 are as described in formula I. As described in Tetrahedron Letters, 2015, 56, 5112, compounds having formula XL are heated with ethyl 2-cyano-3-ethoxyacrylate at elevated temperatures, preferably 140°C, to provide an intermediate having formula LXVII. At the elevated temperatures, preferably between 260°C, in a solvent, preferably diphenyl ether or a diphenyl ether-biphenyl eutectic mixture (Dowtherm) is preferred. The compound having formula LXVII is heated in a medium to give a compound having formula LXVIII. Then, according to methods known to those skilled in the art, for example in the presence of catalytic N,N-dimethylformamide, under reflux, it is converted with thionyl chloride to a compound having formula IIe, similar to US2003 / 212276, page 15.

[0364] For example, compounds having the formula Ih

[0365]

[0366] It can be prepared as shown in Scheme 25.

[0367] Option 25:

[0368]

[0369] Compounds having formula Ih can be prepared according to scheme 25, wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I. In a methanol-water solvent, in the presence of a base (preferably potassium carbonate), similar to WO2011 / 4276, page 132, compounds having formula XLII prepared as in scheme 16 are treated with hydrogen peroxide (in the form of an aqueous solution or a urea adduct) to provide an intermediate having formula LXX. Similar to US2014 / 0275072, paragraph 133, compounds having formula LXX are treated with an aqueous solution of sodium nitrite at low temperature, preferably from 0°C to 5°C, in the presence of an acid such as hydrochloric acid or a mixture of sulfuric acid and acetic acid, to give compounds having formula LXXI. Compounds having formula LXXI are then treated with a suitable activator (e.g., (benzotriazol-1-yloxy)tripyrrolidinylphosphonium hexafluorophosphate). In the presence of a base (e.g., N,N-diisopropylethylamine), coupling with an amine having formula III, similar to the method described in WO2014 / 085528, page 55, yields a compound having formula Ih.

[0370] For example, compounds having formula Ii

[0371]

[0372] It can be prepared as shown in Scheme 26.

[0373] Option 26:

[0374]

[0375] Compounds having formula Ii can be prepared according to scheme 26, wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I. The compound having formula Iaa prepared as described in schemes 1, 5, or 6 is treated with a fluorinating agent, preferably 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octanebis(tetrafluoroborate) (Selectfluor) in a solvent, preferably in acetonitrile, to provide a compound having formula Ii.

[0376] For example, compounds having formula Ij

[0377]

[0378] It can be prepared as shown in Scheme 27.

[0379] Option 27:

[0380]

[0381] Compounds having formula Ij can be prepared according to scheme 27, wherein R1, R2a, R2b, R3, A4, A5, and Q are as described in formula I. Compounds having formula Iaa prepared as in schemes 1, 5, or 6 are treated with a chlorinating agent (preferably N-chlorosuccinimide) in the presence of catalytic dimethyl sulfoxide (DMSO) in a solvent (preferably dichloromethane), similar to Nature Catalysis, 2020, 3, 107, to provide compounds having formula Ij.

[0382] For example, compounds having the formula Im

[0383]

[0384] It can be prepared as shown in Scheme 28.

[0385] Option 28:

[0386]

[0387] Compounds having formula Im can be prepared according to scheme 28, wherein R1, R2a, R2b, R3, A1, A2, A3, A4, and A5 are as described in formula I. Compounds having formula Ik prepared in schemes 1, 3, 5, 6, 20, 21, 22, 25, 26, or 27 are treated with ammonium sulfide in a solvent (preferably pyridine), optionally in the presence of a base (preferably triethylamine), similar to WO2017 / 192385, page 60, to provide compounds having formula Im.

[0388] For example, compounds having the formula In

[0389]

[0390] It can be prepared as shown in Scheme 29.

[0391] Option 29:

[0392]

[0393] Compounds having the formula In can be prepared according to Scheme 29, wherein R1, R2a, R2b, R3, A1, A2, A3, A4, and A5 are as described in Formula I. The compound having the formula Im prepared in Scheme 28 is reacted with 3-bromo-1,1,1-trifluoroacetone in a solvent (preferably N,N-dimethylformamide or acetonitrile), similar to WO2010 / 136817, page 110, to provide a compound having the formula LXXII. The compound having the formula LXXII is treated with trifluoroacetic anhydride in a solvent (preferably tetrahydrofuran or acetonitrile) in the presence of a base (preferably triethylamine), similar to J. Med. Chem. [Journal of Pharmaceutical Chemistry], 2013, 56, 8712, to give a compound having the formula In.

[0394] Depending on the procedure or reaction conditions, the reactants can react in the presence of a base. Examples of suitable bases are alkali metal or alkaline earth metal hydroxides, alkali metal or alkaline earth metal hydrides, alkali metal or alkaline earth metal amides, alkali metal or alkaline earth metal alkoxides, alkali metal or alkaline earth metal acetates, alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal dialkylamides or alkali metal or alkaline earth metal alkylsilylamides, alkylamines, alkylene diamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides, and carbocyclic amines. Examples that may be mentioned are sodium hydroxide, sodium hydride, sodium amino, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamino, potassium bis(trimethylsilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinine ring, N-methylmorpholine, benzyltrimethylammonium hydroxide, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

[0395] These reactants can react with each other as is, i.e., without the addition of solvents or diluents. However, in most cases, it is advantageous to add an inert solvent or diluent, or a mixture of these. If the reaction is carried out in the presence of a base, then these excess bases (such as triethylamine, pyridine, N-methylmorpholine, or N,N-diethylaniline) can also act as solvents or diluents.

[0396] These reactions are advantageously carried out in a temperature range from about -80°C to about +140°C, preferably from about -30°C to about +100°C, and in many cases in the range between ambient temperature and about +80°C.

[0397] 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.

[0398] 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 exchanger, and salts with a base are obtained by treatment with a suitable base or a suitable ion exchanger.

[0399] 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 exchanger reagent), and salts with bases (e.g., by treatment with a suitable acid or a suitable ion exchanger reagent).

[0400] 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 from the reaction mixture.

[0401] Depending on the procedure or reaction conditions, these compounds of formula I with salt-forming properties can be obtained in free form or as salts.

[0402] 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, compounds having Formula I and, where appropriate, their tautomers (in each case, in free or salt form) may exist as one of the possible isomers or as mixtures of these, for example, as pure isomers, such as enantiomers and / or diastereomers, or as mixtures of isomers, such as mixtures of enantiomers, such as racemic mixtures, diastereomer mixtures, or mixtures of racemic mixtures; the present invention relates to pure isomers as well as all possible mixtures of isomers, and should be understood so in each case above and below, even if stereochemical details are not explicitly mentioned in each case.

[0403] A mixture of diastereomers or racemic mixtures 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 racemic mixtures in a known manner, based on the physicochemical differences of these components, for example by stepwise crystallization, distillation and / or chromatography.

[0404] An enantiomer mixture (e.g., a racemic mixture) 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 racemic mixture with an optically active acid (e.g., a carboxylic acid, such as camphoric acid, tartaric acid, or malic acid, or a sulfonic acid, such as camphorsulfonic acid), and the diastereomer mixture that can be obtained in this manner can be separated, for example by stepwise crystallization based on their different solubilities, from which the desired enantiomer can be freed by the action of a suitable reagent (e.g., a basic reagent).

[0405] 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.

[0406] N-oxides can be prepared by reacting a compound having formula I with a suitable oxidizing agent (e.g., H₂O₂ / urea adduct) in the presence of an acid anhydride (e.g., trifluoroacetic anhydride). Such oxidations are known from the literature, for example from J. Med. Chem., 32(12), 2561-73, 1989 or WO 2000 / 15615.

[0407] 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.

[0408] If appropriate, compounds having Formula I and, where appropriate, their tautomers (in free or salt form in each case) 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.

[0409] Compounds having formula I according to Tables D-1 to D-66 below can be prepared according to the method described above. The following examples are intended to illustrate the invention and show preferred compounds having formula I, which are in the form of compounds having formula ID.

[0410]

[0411]

[0412] Table D-1 Twelve compounds with formula IDs D-1.001 to D-1.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Cl, R 2b It is Cl, and Q is as defined in Table Z. For example, D-1.002 is...

[0413]

[0414] Table D-2 Twelve compounds with formula IDs D-2.001 to D-2.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Cl, R 2b It is Cl, and Q is as defined in Table Z.

[0415] Table D-3 Twelve compounds with formula IDs D-3.001 to D-3.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Cl, R 2b It is Cl, and Q is as defined in Table Z.

[0416] Table D-4 Twelve compounds with formula IDs D-4.001 to D-4.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Cl, R 2b It is Cl, and Q is as defined in Table Z.

[0417] Table D-5 Twelve compounds with formula IDs D-5.001 to D-5.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Cl, R 2b It is Cl, and Q is as defined in Table Z.

[0418] Table D-6 Twelve compounds with formula IDs D-6.001 to D-6.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Cl, R 2b It is Cl, and Q is as defined in Table Z.

[0419] Table D-7 Twelve compounds with formula IDs D-7.001 to D-7.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b It is CF3, and Q is as defined in Table Z.

[0420] Table D-8 Twelve compounds with formula IDs D-8.001 to D-8.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It's CF3, R 2b It is CF3, and Q is as defined in Table Z.

[0421] Table D-9 Twelve compounds with formula IDs D-9.001 to D-9.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b It is CF3, and Q is as defined in Table Z.

[0422] Table D-10 Twelve compounds with formula IDs D-10.001 to D-10.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b It is CF3, and Q is as defined in Table Z.

[0423] Table D-11 Twelve compounds with formula IDs D-11.001 to D-11.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R... 2a It's CF3, R 2b It is CF3, and Q is as defined in Table Z.

[0424] Table D-12Twelve compounds with formula IDs D-12.001 to D-12.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b It is CF3, and Q is as defined in Table Z.

[0425] Table D-13 Twelve compounds with formula IDs D-13.001 to D-13.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b It is Cl, and Q is as defined in Table Z.

[0426] Table D-14 Twelve compounds with formula IDs D-14.001 to D-14.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It's CF3, R 2b It is Cl, and Q is as defined in Table Z.

[0427] Table D-15 Twelve compounds with formula IDs D-15.001 to D-15.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b It is Cl, and Q is as defined in Table Z.

[0428] Table D-16 Twelve compounds with formula IDs D-16.001 to D-16.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b It is Cl, and Q is as defined in Table Z.

[0429] Table D-17 Twelve compounds with formula IDs D-17.001 to D-17.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, and R... 2a It's CF3, R 2b It is Cl, and Q is as defined in Table Z.

[0430] Table D-18Twelve compounds with formula IDs D-18.001 to D-18.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b It is Cl, and Q is as defined in Table Z.

[0431] Table D-19 Twelve compounds with formula IDs D-19.001 to D-19.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Cl, R 2b It is CF3, and Q is as defined in Table Z.

[0432] Table D-20 Twelve compounds with formula IDs D-20.001 to D-20.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Cl, R 2b It is CF3, and Q is as defined in Table Z.

[0433] Table D-21 Twelve compounds with formula IDs D-21.001 to D-21.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Cl, R 2b It is CF3, and Q is as defined in Table Z.

[0434] Table D-22 Twelve compounds with formula IDs D-22.001 to D-22.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Cl, R 2b It is CF3, and Q is as defined in Table Z.

[0435] Table D-23 Twelve compounds with formula IDs D-23.001 to D-23.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, and R... 2a It is Cl, R 2b It is CF3, and Q is as defined in Table Z.

[0436] Table D-24Twelve compounds with formula IDs D-24.001 to D-24.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Cl, R 2b It is CF3, and Q is as defined in Table Z.

[0437] Table D-25 Twelve compounds with formula IDs D-25.001 to D-25.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Cl, R 2b It is Br, and Q is as defined in Table Z.

[0438] Table D-26 Twelve compounds with formula IDs D-26.001 to D-26.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Cl, R 2b It is Br, and Q is as defined in Table Z.

[0439] Table D-27 Twelve compounds with formula IDs D-27.001 to D-27.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Cl, R 2b It is Br, and Q is as defined in Table Z.

[0440] Table D-28 Twelve compounds with formula IDs D-28.001 to D-28.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Cl, R 2b It is Br, and Q is as defined in Table Z.

[0441] Table D-29 Twelve compounds with formula IDs D-29.001 to D-29.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, and R... 2a It is Cl, R 2b It is Br, and Q is as defined in Table Z.

[0442] Table D-30Twelve compounds with formula IDs D-30.001 to D-30.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Cl, R 2b It is Br, and Q is as defined in Table Z.

[0443] Table D-31 Twelve compounds with formula IDs D-31.001 to D-31.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Br, R 2b It is Cl, and Q is as defined in Table Z.

[0444] Table D-32 Twelve compounds with formula IDs D-32.001 to D-32.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Br, R 2b It is Cl, and Q is as defined in Table Z.

[0445] Table D-33 Twelve compounds with formula IDs D-33.001 to D-33.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Br, R 2b It is Cl, and Q is as defined in Table Z.

[0446] Table D-34 Twelve compounds with formula IDs D-34.001 to D-34.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Br, R 2b It is Cl, and Q is as defined in Table Z.

[0447] Table D-35 Twelve compounds with formula IDs D-35.001 to D-35.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Br, R 2b It is Cl, and Q is as defined in Table Z.

[0448] Table D-36Twelve compounds with formula IDs D-36.001 to D-36.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Br, R 2b It is Cl, and Q is as defined in Table Z.

[0449] Table D-37 Twelve compounds with formula IDs D-37.001 to D-37.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b It is Br, and Q is as defined in Table Z.

[0450] Table D-38 Twelve compounds with formula IDs D-38.001 to D-38.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It's CF3, R 2b It is Br, and Q is as defined in Table Z.

[0451] Table D-39 Twelve compounds with formula IDs D-39.001 to D-39.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b It is Br, and Q is as defined in Table Z.

[0452] Table D-40 Twelve compounds with formula IDs D-40.001 to D-40.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b It is Br, and Q is as defined in Table Z.

[0453] Table D-41 Twelve compounds with formula IDs D-41.001 to D-41.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, and R... 2a It's CF3, R 2b It is Br, and Q is as defined in Table Z.

[0454] Table D-42Twelve compounds with formula IDs D-42.001 to D-42.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b It is Br, and Q is as defined in Table Z.

[0455] Table D-43 Twelve compounds with formula IDs D-43.001 to D-43.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Br, R 2b It is CF3, and Q is as defined in Table Z.

[0456] Table D-44 Twelve compounds with formula IDs D-44.001 to D-44.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Br, R 2b It is CF3, and Q is as defined in Table Z.

[0457] Table D-45 Twelve compounds with formula IDs D-45.001 to D-45.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Br, R 2b It is CF3, and Q is as defined in Table Z.

[0458] Table D-46 Twelve compounds with formula IDs D-46.001 to D-46.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Br, R 2b It is CF3, and Q is as defined in Table Z.

[0459] Table D-47 Twelve compounds with formula IDs D-47.001 to D-47.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Br, R 2b It is CF3, and Q is as defined in Table Z.

[0460] Table D-48Twelve compounds with formula IDs D-48.001 to D-48.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Br, R 2b It is CF3, and Q is as defined in Table Z.

[0461] Table D-49 Twelve compounds with formula IDs D-49.001 to D-49.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Br, R 2b It is Br, and Q is as defined in Table Z.

[0462] Table D-50 Twelve compounds with formula IDs D-50.001 to D-50.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Br, R 2b It is Br, and Q is as defined in Table Z.

[0463] Table D-51 Twelve compounds with formula IDs D-51.001 to D-51.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Br, R 2b It is Br, and Q is as defined in Table Z.

[0464] Table D-52 Twelve compounds with formula IDs D-52.001 to D-52.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is Br, R 2b It is Br, and Q is as defined in Table Z.

[0465] Table D-53 Twelve compounds with formula IDs D-53.001 to D-53.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is Br, R 2b It is Br, and Q is as defined in Table Z.

[0466] Table D-54Twelve compounds with formula IDs D-54.001 to D-54.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is Br, R 2b It is Br, and Q is as defined in Table Z.

[0467] Table D-55 Twelve compounds with formula IDs D-55.001 to D-55.012 are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b I is Q, and Q is as defined in Table Z.

[0468] Table D-56 Twelve compounds with formula IDs D-56.001 to D-56.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It's CF3, R 2b I is Q, and Q is as defined in Table Z.

[0469] Table D-57 Twelve compounds with formula IDs D-57.001 to D-57.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b I is Q, and Q is as defined in Table Z.

[0470] Table D-58 Twelve compounds with formula IDs D-58.001 to D-58.012 are provided, where A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It's CF3, R 2b I is Q, and Q is as defined in Table Z.

[0471] Table D-59 Twelve compounds with formula IDs D-59.001 to D-59.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, and R... 2a It's CF3, R 2b I is Q, and Q is as defined in Table Z.

[0472] Table D-60Twelve compounds with formula IDs D-60.001 to D-60.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It's CF3, R 2b I is Q, and Q is as defined in Table Z.

[0473] Table D-61 Twelve compounds, D-61.001 to D-61.012, with formula IDs are provided, where A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is H, and R... 2a It is I, R 2b It is CF3, and Q is as defined in Table Z.

[0474] Table D-62 Twelve compounds with formula IDs D-62.001 to D-62.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is I, R 2b It is CF3, and Q is as defined in Table Z.

[0475] Table D-63 Twelve compounds with formula IDs D-63.001 to D-63.012 are provided, wherein A1 is N, A2 is CH, A3 is CH, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is I, R 2b It is CF3, and Q is as defined in Table Z.

[0476] Table D-64 Twelve compounds with formula IDs D-64.001 to D-64.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is H, and R... 2a It is I, R 2b It is CF3, and Q is as defined in Table Z.

[0477] Table D-65 Twelve compounds with formula IDs D-65.001 to D-65.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH3, R... 2a It is I, R 2b It is CF3, and Q is as defined in Table Z.

[0478] Table D-66Twelve compounds with formula IDs D-66.001 to D-66.012 are provided, wherein A1 is N, A2 is CH, A3 is N, A4 is CH, A5 is CH, R1 is CH2-cyclopropyl, and R... 2a It is I, R 2b It is CF3, and Q is as defined in Table Z.

[0479] Table Z Definition of substituents for Q:

[0480]

[0481]

[0482] Certain intermediate compounds having formulas II(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i) can also be obtained, some of which are novel. For example,

[0483] Compounds having formula II(i), where (i)X1 is Cl and A1, A2, A3, A4, A5, R 2a and R 2b It is as defined in any of the items in Tables D-1 to D-66; (ii) where (i) X1 is Br and A1, A2, A3, A4, A5, R 2a and R 2b It is as defined in any of the items in Tables D-1 to D-66.

[0484]

[0485] Compounds having formula III(i), wherein (i) R1 is H and Q is as defined in Table Z; (ii) wherein (i) R1 is CH3 and Q is as defined in Table Z; and (iii) wherein (i) R1 is CH2-cyclopropyl and Q is as defined in Table Z.

[0486]

[0487] Compounds having formula IV(i), wherein A1, A2, A3, A4, A5, R 2a and R 2b It is as defined in any of the items in Tables D-1 to D-66.

[0488]

[0489] Compounds having formula V(i), wherein (i)X2 is Cl and Q is as defined in Table Z; (ii) wherein (i)X2 is Br and Q is as defined in Table Z; and (iii) wherein (i)X2 is I and Q is as defined in Table Z.

[0490]

[0491] Compounds having formula VII(i), where Q is as defined in Table Z.

[0492]

[0493] Compounds having formula XI(i), wherein A1, A2, A3, A4, A5, R1, R 2a and R 2b It is as defined in any of the items in Tables D-1 to D-66.

[0494]

[0495] Compounds having formula XIV(i), wherein A1, A2, A3, A4, A5, R1, R 2a and R 2b It is as defined in any of the items in Tables D-1 to D-66.

[0496]

[0497] On the other hand, the present invention correspondingly provides compounds having formulas II(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i), wherein in each case, where applicable, A1, A2, A3, A4, A5, R1, R 2a and R 2b Q is as defined in the first aspect for Formula I; and for Formula II(i), X1 is a halogen, preferably chlorine or bromine. Furthermore, the corresponding embodiments shown for Formula I are also applicable to compounds having Formulas II(i), III(i), IV(i), V(i), VII(i), XI(i), and XIV(i).

[0498] The compounds of Formula I according to the present invention are active ingredients with preventative and / or therapeutic value in the field of pest control. Even at low application rates, they exhibit a very favorable biocidal spectrum and are well tolerated by warm-blooded species, fish, and plants. These active ingredients according to the present invention act on all or individual developmental stages of normally susceptible and resistant animal pests (such as insects or representatives of mites). The insecticidal or acaricidal activity of the active ingredients according to the present invention can manifest directly, i.e., immediate or only after some time (e.g., during molting), causing damage to pests; or indirectly, for example, by reducing oviposition and / or hatching rates.

[0499] Examples of animal pests mentioned above are:

[0500] From the order Acari, for example,

[0501] Species of the genera *Acalitus*, *Aculus*, *Acaricalus*, *Aceria*, *Acarus siro*, *Amblyomma*, *Argas*, *Boophilus*, *Brevipalpus*, *Bryobia*, *Calipitrimerus*, *Chorioptes*, *Dermanyssusgallinae*, *Dermatophagoides*, *Eotetranychus*, and *Eriophyes*. Species of the genera *Hemitarsonemus*, *Hyalomma*, *Ixodes*, *Olygonychus*, *Ornithodoros*, *Polyphagotarsone latus*, *Panonychus*, *Phyllocoptruta oleivora*, *Phytonemus*, *Polyphagotarsonemus*, *Psoroptes*, *Rhipicephalus*, *Rhizoglyphus*, and *Sarcoptes*. spp.), species of the genera *Steneotarsonemus*, *Tarsonemus*, and *Tetranychus*;

[0502] From lice, for example,

[0503] Species of the genera *Haematopinus* spp., *Linognathus* spp., *Pediculus* spp., *Pemphigus* spp., and *Phylloxera* spp.;

[0504] From Coleoptera, for example,

[0505] Species of the genera *Agriotes* spp., *Amphimallon majale*, *Anomala orientalis*, *Anthonomus* spp., *Aphodius* spp., *Astylus atromaculatus*, *Ataenius* spp., *Atomaria linearis*, *Chaetocnema tibialis*, *Cerotomas* spp., *Conoderus* spp., *Cosmopolites* spp., *Cotinis nitida*, *Curculio* spp., *Cyclocephalas* spp., *Dermestes* spp., and *Diabrotica*. spp.), Argentine rhinoceros beetle (Diloboderus abderus), phytophagous ladybug species (Epilachna spp.), Eremnus species, black cane beetle (Heteronychus arator), coffee berry beetle (Hypothenemus hampei), Lagria vilosa, potato beetle (Leptinotarsa ​​decemlineata), rice weevil species (Lissorhoptrus spp.), Liogenys species, Maecolaspis species, chestnut velvet beetle (Maladera castanea), American leaf beetle species (Megascelis spp.), rapeseed flower beetle (Melighetes aeneus), dwarf beetle species (Melolontha spp.), Myochrousarmatus, sawmill beetle species (Orycaephilus spp.), ear-beaked weevil species (Otiorhynchus spp.), dwarf horned beetle species (Phyllophaga spp.), species of the genus *Phlyctinus*, species of the genus *Popillia*, species of the genus *Psylliodes*, species of the genus *Rhyssomatus aubtilis*, species of the genus *Rhizopertha*, family Scarabidae, species of the genus *Sitophilus*, and species of the genus *Sitotroga*.), species of the genera *Somaticus*, *Sternechus subsignatus*, *Tenebrio*, *Tribolium*, and *Trogoderma*.

[0506] From the order Diptera, for example,

[0507] Species of the genera *Aedes*, *Anopheles*, *Antherigonasoccata*, *Bactrocea oleae*, *Bibio hortulanus*, *Bradysia*, *Calliphora erythrocephala*, *Ceratitis*, *Chrysomyia*, *Culex*, *Cuterebra*, *Dacus*, *Delia*, *Drosophila melanogaster*, *Fannia*, *Gastrophilus*, *Geomyza tripunctata*, and *Glossina*. spp.), Hypodermas spp., Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp., Musca spp., Oestrus spp., Orseolia spp., Oscinella frit., Pegomyia hyoscyami, Phorbia spp., Rhagoletis spp., Riveria quadrifasciata, Scatella spp., Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp. spp.) and species of the genus Tipula spp.;

[0508] From Hemiptera, for example,

[0509] *Acanthocoris scabrator*, *Acrosternum* species, *Adelphocoris lineolatus*, *Aleurodes* species, *Amblypelta nitida*, *Bathycoelia thalassina*, *Clavigrallatomentosicollis*, *Creontiades* species, *Dichelops furcatus*, *Edessa* species, *Euchistus* species, *Eurydema pulchrum*, *Platyscutellatus* species, *Tea-winged Bug*, *Horcias* Species of the genera *nobilellus*, *Rhizophora*, *Nesidiocoris tenuis*, *Nysius simulans*, *Ipomoea*, *Dermacus*, *Nesidiocoris tenuis*, *Nesidiocoris*, *Nesidiocoris simulans*, *Nesidiocoris ...

[0510] Pea webless long-tubed aphid (Acyrthosium pisum), species of the genus *Adalges*, *Agalliana ensigera*, *Talgilong vein psyllid*, species of the genus *Aleurodicus*, species of the genus *Aleurocanthus*, sugarcane hole whitefly, soft-haired whitefly (Aleurothrixus floccosus), cabbage whitefly (Aleyrodes brassicae), cotton leafhopper (Amarasca biguttula), lemon long-spotted leafhopper, species of the genus *Nephrodisiac*, aphids, species of the genus *Aspidiotus*, eggplant webless aphid, potato / tomato psyllid (Bactericera cockerelli), species of the genus *Small whitefly*, species of the genus *Brachycaudus*, cabbage aphid, species of the genus *Cavariella*, two-tailed aphid (Cavariella aegopodii) Scop.), species of the genus *C.*, ... Maidis, species of the genera *Metcalfa pruinosa*, ...), Pear Green Aphid, Odonaspis ruthae, Sugarcane Cotton Aphid, Myrica Marginata Whitefly, Cox's Psyllid, Species of the genus *Pseudatomoscelis*, Species of the genus *Gallus*, Corn Lanternfly, Species of the genus *Phylloxera*, Species of the genus *Phylloxera*, Species of the genus *Phylloxera*, Species of the genus *Pseudatomoscelis*, Species of the genus *Pulvinaria*, Species of the genus *Pulvinaria*, Species of the genus *Quesada gigas*, Species of the genus *Reciliadorsalis*, Species of the genus *Pseudatomoscelis*, Species of the genus *Pseudatomoscelis*, Species of the genus *Pulvinaria*, Species of the genus *Pulvinaria*, Species of the genus *Pleurotus*, Species of the genus *Pseudatomoscelis ... Proserpina), species of the genus *Proserpina*, species of the genus *Tridiscus* sporoboli, species of the genus *Trionymus* spp., African psyllids, arrowhead scales, flame leafhoppers, and *Zyginidia scutellaris*.

[0511] From Hymenoptera, for example,

[0512] Species from the genera *Acromyrmex*, *Arge* spp., *Attaspp.*, *Cephus* spp., *Diprion* spp., *Diprionidae*, *Gilpinia polytoma*, *Hoplocampa* spp., *Lasius* spp., *Monomorium pharaonis*, *Neodiprions* pp., *Pogonomyrmex* spp., *Solenopsis* spp., and *Vespa* spp.;

[0513] From the order Isoptera, for example,

[0514] Species of the genera *Coptotermes* spp., *Corniternes cumulans*, *Incisitermes* spp., *Macrotermes* spp., *Mastotermes* spp., *Microtermes* spp., and *Reticulitermes* spp.; tropical fire ant (*Solenopsis geminate*).

[0515] From the order Lepidoptera, for example,

[0516] Species of the genera *Longwinged Roller*, *Brown-banded Roller*, *Clearwing Moth*, *Noctuid Moth*, cotton leafhopper, *Amylois*, *Lysimachia*, *Yellow Roller*, *Argyresthia spp.*, *Betweenleaf Roller*, *Striped Roller*, cotton leafminer, corn leafminer, powdery leafminer, peach fruit borer, *Grass moth*, *Colored Roller*, *Chrysoteuchia topiaria*, grape fruit borer, *Leaf Roller*, *Cloud Roller*, *Striped Roller*, *Sheath Moth*, *Colias lesbia*, *Cosmophila* Species of the genera *Flava*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Catharanthus*, *Elasmopalpus*, *Elasmopalpus*, *Catharanthus*, *Epinotia*, *Estigmene acrea*, *Etiellazinckinella*, *Epinotia*, *Epinotia*, *Estigmene acrea*, *Etiellazinckinella*, *Epinotia*, *Epinotia*, *Epinotia*, *Estigmene ... *Lignosellus*, *Leaf Miner*, *Leaf Miner* species, *Grape Flower Roller*, *Loxostege bifidalis*, *Tortoise Moth* species, *Minter* species, *Malacosoma* spp., *Cabbage Noctuid*, *Tobacco Hawk Moth*, *Mythimna* spp., *Noctuid* species, *Autumn Geyser* species, *Orniodes indica*, European Corn Borer, *Small Leaf Roller* species, *Brown Leaf Roller* species, *Small-eyed Noctuid*, *Stem-boring Noctuid*, *Red Bollworm*, *Coffee Leaf Miner*, *One-spotted Armyworm*, *Potato Leaf Moth*, *Cabbage White*, *White Leaf Butterfly* species, *Plutella xylostella*, *Small White Nest Moth* species, *Geometrid Leaf Moth* species, *Rachiplusianu*, *Richia albicosta*, *Scirpophaga* species spp.), species of the genera *Steel borer*, *Long-haired leafroller*, *Grey-winged leafroller*, *Cotton leafroller*, *Clearwinged moth*, *Heterodactylus*, *Roller moth*, *Powdered leafroller*, *Tomato leafminer*, and *Ophiopogon*.

[0517] From the order Mallophaga, for example,

[0518] Species of the genera *Damalinea* and *Trichodectes*;

[0519] From the order Orthoptera, for example,

[0520] Species of the genera *Blatta*, *Blattella*, *Gryllotalpa*, *Leucophaea maderae*, *Locusta*, *Neocurtilla hexadactyla*, *Periplaneta*, *Scapteriscus*, and *Schistocerca*;

[0521] From the order Psocoptera, for example,

[0522] Species of the genus *Liposcelis*;

[0523] From the order Siphonaptera, for example,

[0524] Species of the genera *Ceratophyllus* spp., *Ctenocephalides* spp., and *Xenopsylla cheopis*;

[0525] From the order Thysanoptera, for example,

[0526] Calliothrips phaseoli, species of the genera *Frankliniella*, species of the genera *Heliothrips*, species of the genera *Hercinothrips*, species of the genera *Parthenothrips*, species of the genera *Scirtothrips aurantii*, species of the genera *Sericothrips variabilis*, species of the genera *Taeniothrips*, and species of the genera *Thripsspp*.

[0527] From the order Thysanura, for example, silverfish (Lepisma saccharina).

[0528] In another aspect, the present invention may also relate to a method for controlling damage to plants and their parts caused by plant parasitic nematodes (endoparasitic, semi-endoparasitic, and ectoparasitic nematodes), particularly the following plant parasitic nematodes: root knot nematodes, northern root knot nematode (Meloidogyne hapla), southern root knot nematode (Meloidogyne incognita), Javan root knot nematode (Meloidogyne javanica), peanut root knot nematode (Meloidogyne arenaria), and other root knot nematode species; cyst-forming nematodes, potato golden nematode (Globodera rostochiensis), and other Globodera species; cereal cyst nematode (Heterodera avenae), soybean cyst nematode (Heteroderaglycines), and beet cyst nematode (Heterodera... *Heterodera trifolii* and other species of the genus *Heterodera*; *Seed gall nematodes* and *Anguina* species; *Stem and foliar nematodes* and *Aphelenchoides* species; *Sting nematodes*, *Belonolaimus longicaudatus* and other species of the genus *Belonolaimus*; *Pine nematodes*, *Bursaphelenchus xylophilus* and other species of the genus *Bursaphelenchus*; *Ring nematodes*. Species of the genera *Criconema*, *Criconemella*, *Criconemoides*, and *Mesocriconema*; *Stemand bulb nematodes*, *Ditylenchus destructor*, *Ditylenchus dipsaci*, and other *Ditylenchus* species; *Awl nematodes* and *Dolichodorus* species;Spiral nematodes, Heliocotylenchus multicinctus and other species of the genus *Helicotylenchus*; Sheath and sheathoid nematodes, species of the genus *Hemicycliophora* and *Hemicriconemoides*; species of the genus *Hirshmanniella*; species of the genus *Lancenematodes* and *Hoploaimus*; species of the genus *false rootknot nematodes* and *Nacobbus*; Needle nematodes, Longidoruselongatus and other species of the genus *Longidorus*; Pin nematodes and species of the genus *Pratylenchus*; Lesion nematodes. * *Pratylenchus neglectus*, *Pratylenchus penetrans*, *Pratylenchus curvitatus*, *Pratylenchus goodeyi*, and other species of the genus *Pratylenchus*; *Burrowing nematodes*, *Radipholus similis*, and other species of the genus *Radipholus*; *Reniform nematodes*, *Rotylenchus robustus*, *Rotylenchus reniformis*, and other species of the genus *Rotylenchus*; species of the genus *Scutellonema*; *Stubby root nematodes*, *Trichodorus*, and other species of the genus *Trichodorus*. primitivus) and other species of the genus *Trichodorus*, species of the genus *Paratrichodorus*; Stunt nematodes, Tylenchorhynchus claytoni, Tylenchorhynchus dubius and other species of the genus *Tylenchorhynchus*;Citrus nematode species (Citrus nematodes, Tylenchulus); Dagger nematodes and Xiphinema species; and other plant-parasitic nematode species, such as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius spp., Punctodera spp., and Quinisulcius spp.

[0529] The compounds of this invention also possess activity against mollusks. Examples include, for instance, the family Pomacea canaliculata; the family Arionidae (including the black slug *A. ater*, the ringed slug *A. circumscriptus*, the brown slug *A. hortensis*, and the red slug *A. rufus*); and the family Bradybaenidae (including the shrubby slug *Bradybaena*). fruticum); Cepaea (C. hortensis, C. Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D. laeve, D. reticulatum); Discus (D. rotundatus); Euophalia; Galba (G. trunculata); Heliclia (H. itala, H. obvia); Helicigona (Helicidae) arbustorum); Helicodiscus; Helix (H. aperta); Limax (L. cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus); Lymnaea; Milax (M. gamblings, M. marginatus, M. sowerbyi); Opeas; Pomacea (P. canaticulata); Vallonia and Zanitoides.

[0530] The active ingredients according to the invention can be used to control, i.e., to suppress or destroy pests of the types described above, which are particularly found on plants, especially on useful and ornamental plants in agriculture, horticulture and forestry, or on organs of these plants, such as fruits, flowers, leaves, stems, tubers or roots, and in some cases, even plant organs formed at a later point in time remain protected against these pests.

[0531] In particular, suitable target crops are: cereals such as wheat, barley, rye, oats, rice, corn, or sorghum; sugar beets such as sugar beets or forage beets; fruits such as pome, stone fruits, or seedless small fruits such as apples, pears, plums, peaches, apricots, cherries, or berries such as strawberries, raspberries, or blackberries; legumes such as beans, lentils, peas, or soybeans; and oilseed crops such as rapeseed, mustard, poppies, olives, sunflowers, coconuts, castor beans, and cocoa beans. Or peanuts; cucurbit crops, such as pumpkins, cucumbers, or melons; fiber plants, such as cotton, flax, hemp, or jute; citrus fruits, such as oranges, lemons, grapefruits, or tangerines; vegetables, such as spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, or bell peppers; Lauraceae, such as avocados, cinnamon, or camphor; and also tobacco, nuts, coffee, eggplant, sugarcane, tea, pepper, grapevines, hops, plantains, and latex plants.

[0532] The compositions and / or methods of the present invention can also be used on any ornamental plants and / or vegetable crops (including flowers, shrubs, broad-leaved trees and evergreens).

[0533] For example, this invention can be used for any of the following ornamental plant species: Ageratum species, Alonsoa spp. species, Anemone species, Anisodontea capsenisis, Chrysanthemum species, Snapdragon species, Aster species, Begonia species (e.g., Rieger begonia, Begonia semperflorens, B. tubéreux), Bougainvillea species, Brachycome spp. species, Brassica species (ornamental plants), Calceolaria species, Chili pepper, Vinca minor, Canna species, Cornflower species, Chrysanthemum species, Cineraria species (C. maritime), Coreopsis species, Crassula coccinea, Cupeaignea, Dahlia species, Delphinium species, Bleeding heart, Dorotheantus species spp.), lisianthus, forsythia species, fuchsia species, geranium gnaphalium, semperflorens species, globe amaranth, heliotrope species, sunflower species, hibiscus species, hydrangea species, hydrangea species, crape myrtle species, impatiens species (African impatiens), Iresines spp., kalanchoe species, lantana, Marchflower, lion's ear flower species, lily species, pine needle chrysanthemum species, ground cherry species, peppermint species, dragon's face chrysanthemum species, marigold species, carnation species, canna species, oxalis species, daisy species, geranium species (shield geranium, horseshoe geranium), violet species (pansy), petunia species, oleander species, peperomia species spp.), species of the genera *Poinsettia*, *Parthenocissus* (including five-leaved *Parthenocissus* and *Parthenocissus tricuspidata*), species of the genera *Primula*, *Rhododendron*, species of the genera *Rosa*, species of the genera *Datura*, species of the genera *Viola*, species of the genera *Salvia*, *Scaevola aemola*, *Schizanthus wisetonensis*, species of the genera *Sedum*, species of the genera *Solanum*, species of the genera *Surfinia*, species of the genera *Marigold*, species of the genera *Nicotiana*, species of the genera *Verbena*, species of the genera *Zinnia*, and other flower bed plants.

[0534] For example, this invention can be used for any of the following vegetable species: Allium species (garlic, onion, A. oschaninii, leek, shallot, scallion), fennel, celery (Apium graveolus), asparagus, beet (Beta vulgarus), Brassica species (cabbage, Chinese cabbage, turnip), chili pepper, chickpea, endive, chicory species (chicory, endive), watermelon, cucumber species (cucumber, melon), squash species (zucchini, squash), artichoke species (Cyanara spp.), wild carrot, fennel, St. John's wort species, lettuce, tomato species (tomato, cherry tomato), mint species, basil, parsley, bean species (bean, green bean), pea, radish, edible rhubarb, rosemary species, sage species, black ginseng (Scorzonera) Hispanica), eggplant, spinach, species of the genus *Vallisneria* (Vallisneria eriocarpa), and broad beans.

[0535] Preferred ornamental plant species include African violet, Begonia, Dahlia, Sedum, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia, Aster, Cornflower, Coreopsis, Delphinium, Mentha, Oleander, Yellow Daisy, Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum, Ranunculus, Fuchsia, Sage, Hydrangea, Rosemary, Sage, St. John's wort, Mint, Sweet pepper, Tomato, and Cucumber.

[0536] The active ingredients according to the invention are particularly suitable for controlling bean aphids, cucumber leaf beetles, tobacco shoot moths, peach aphids, diamondback moths, and sea takin moths on cotton, vegetables, corn, rice, and soybean crops. These active ingredients according to the invention are also particularly suitable for controlling cabbage leafminer (preferably on vegetables), codling moths (preferably on apples), small green leafhoppers (preferably in vegetables and vineyards), potato leaf beetles (preferably on potatoes), and rice stem borers (preferably on rice).

[0537] Compounds having formula I are particularly suitable for control:

[0538] • Harmful organisms of the order Hemiptera, such as one or more of the following species: whitefly (Bemisia tabaci), bean aphid, peach aphid, rice constrictor aphid (Rhopalosiphum Padi), brown rice fly (Nilaparvata lugens), and hero bug (Euschistus heros) (preferably on vegetables, soybeans, and sugarcane);

[0539] • Lepidoptera pests, such as one or more of the following species: sea gray-winged moth, fall armyworm (Spodoptera frugiperda), diamondback moth, rice leaf roller (Cnaphalocrocis medinalis), codling moth, soybean looper (Chrysodeixis includes), rice stem borer, South American corn seedling borer (Elasmopalpuslignosellus), soybean looper (Pseudoplusia includens), and tomato leafminer (preferably on vegetables and corn);

[0540] • Harmful organisms of the order Thysanoptera, such as one or more of the family Thrips, including *Thrips sphaeroides* and *Thrips serratus* (preferably on vegetables); and

[0541] • Soil pests (such as Coleoptera), such as species like the cucumber leaf beetle, species of the genus *Tectus*, and the potato beetle (preferably on vegetables and corn).

[0542] 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 originate from toxin-producing bacteria, particularly those of the genus Bacillus.

[0543] Toxins that can be expressed by such transgenic plants include, for example, insecticidal proteins, such as those from Bacillus cereus or Bacillus thuringiensis; or insecticidal proteins from Bacillus thuringiensis, such as δ-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 bacterial colonizing nematodes, such as species of the genus Photorhabdus or species of the genus Xenorhabdus, such as Photorhabdus luminescens and Xenorhabdus nematodes. (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.

[0544] In the context of this invention, δ-endotoxins, such as Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1, or Cry9C, or vegetative insecticidal proteins (Vip), such as 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 the different domains of those proteins (see, for example, WO 02 / 15701). 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, a cathepsin-G-recognition sequence is inserted into the Cry3A toxin (see WO 03 / 018810).

[0545] 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 03 / 052073.

[0546] 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.

[0547] Toxins, including those found in genetically modified plants, enable the plants to tolerate harmful insects. Such insects can exist in any insect taxonomy, but are particularly common in beetles (Coleoptera), dipterans (Diptera), and moths (Lepidoptera).

[0548] Transgenic plants containing one or more genes encoding resistance to insecticides and expressing one or more toxins are known, and some of these are commercially available. Examples of such plants are: (Corn variety expressing Cry1Ab toxin); YieldGard (A maize variety expressing the Cry3Bb1 toxin); YieldGard (A maize variety that expresses Cry1Ab and Cry3Bb1 toxins); (A maize variety that expresses the Cry9C toxin); Herculex (A maize variety that expresses the Cry1Fa2 toxin and acquires the enzyme phosphinic acid N-acetyltransferase (PAT) to develop resistance to the herbicide glufosinate-ammonium salt); NuCOTN (Cotton variety expressing Cry1Ac toxin); Bollgard (Cotton variety expressing Cry1Ac toxin); Bollgard (Cotton variety expressing Cry1Ac and Cry2Ab toxins); (Cotton variety expressing Vip3A and Cry1Ab toxins); (Potato variety that expresses Cry3A toxin); GT Advantage (GA21 glyphosate resistance) CB Advantage (Bt11 corn borer (CB) traits) and

[0549] Other examples of such genetically modified crops are:

[0550] 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.

[0551] 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 transgenic to resist the European corn borer (corn borer and mealybug). Bt176 maize is also transgenic to express the enzyme PAT to gain tolerance to the herbicide glufosinate-ammonium.

[0552] 3. MIR604 maize, from Syngenta Seed Company, 27 Hobbit Road, F-31 790 Saint-Soville, France, registration number 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 03 / 018810.

[0553] 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.

[0554] 5. IPC 531 cotton, from Monsanto Europe, 270-272 Tefallen Boulevard, B-1150 Brussels, Belgium, registration number C / ES / 96 / 02.

[0555] 6. 1507 maize, from Pioneer Overseas Corporation, Avenue Tedesco, 7B-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.

[0556] 7. NK603 × MON 810 maize, from Monsanto Europe, 270-272 Teflon Boulevard, B-1150 Brussels, Belgium, registration number C / GB / 02 / M3 / 03. It was created by crossing the genetically modified variety NK603 with MON 810, resulting in a conventionally bred hybrid maize variety. NK603 × MON 810 maize transgenically expresses the protein CP4 EPSPS obtained from the Agrobacterium strain CP4, thus enabling herbicide tolerance. (Contains glyphosate), as well as Cry1Ab toxin obtained from Bacillus thuringiensis Kurstak subsp., which makes it resistant to certain lepidopteran insects, including the European corn borer.

[0557] Transgenic crops of insect-resistant plants were also described in BATS (Zentrum für Biosicherheit und Nachhaltigkeit, BATS Center, Clarastrasse 13, Basel 4058, Switzerland) report 2003. http: / / bats.ch )middle.

[0558] The term "crop" should be understood to also include crop plants that have been transformed using recombinant DNA technology to enable them to synthesize selectively active resistance substances, such as so-called "pathogenesis-associated proteins" (PRPs, see, for example, EP-A-0 392 225). Examples of such resistance substances and transgenic plants capable of synthesizing such resistance substances are known, for example, from EP-A-0 392 225, WO 95 / 33818, and EP-A-0 353 191. Methods for producing such transgenic plants are generally known to those skilled in the art and are described in, for example, the disclosures mentioned above.

[0559] Crops can also be modified to increase their resistance to pathogens such as fungi (e.g., Fusarium, Anthracnose, or Phytophthora), bacteria (e.g., Pseudomonas), or viruses (e.g., Potato Leaf Roll Virus, Tomato Spotted Wilt Virus, Cucumber Mosaic Virus).

[0560] Crops also include those that have increased resistance to nematodes such as soybean heterodera.

[0561] Crops that are tolerant to abiotic stresses include those that have increased tolerance to drought, high salinity, high temperature, cold, frost or light radiation, for example, through the expression of NF-YB or other proteins known in the art.

[0562] Antipathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers, such as sodium and calcium channel blockers, such as viral KP1, KP4 or KP6 toxins; stilbene synthase; bibenzyl synthase; chitinase; glucanase; so-called "pathogenesis-associated proteins" (PRP; see, for example, EP-A-0 392 225); antipathogenic substances produced by microorganisms, such as peptide antibiotics or heterocyclic antibiotics (see, for example, WO 95 / 33818) or proteins or polypeptide factors involved in plant pathogen defense (so-called "plant disease resistance genes", as described in WO 03 / 000906).

[0563] Other applications of the compositions according to the invention include the protection of stored articles and storage rooms, as well as the protection of raw materials such as timber, textiles, flooring, or buildings, and also in the field of hygiene, particularly the protection of humans, livestock, and productive animals from the types of pests mentioned.

[0564] This invention provides compounds for use in a first aspect of therapy. This invention provides compounds for controlling parasites internal or external to an animal. This invention further provides compounds for controlling external parasites in an animal. This invention further provides compounds for preventing and / or treating diseases transmitted by external parasites.

[0565] This invention provides the use of the compound of the first aspect for manufacturing a medicament for controlling parasites inside or on the surface of animals. This invention further provides the use of the compound of the first aspect for manufacturing a medicament for controlling ectoparasites in animals. This invention further provides the use of the compound of the first aspect for manufacturing a medicament for preventing and / or treating diseases transmitted by ectoparasites.

[0566] This invention provides the use of the compound of the first aspect in controlling parasites inside or on the surface of animals. This invention further provides the use of the compound of the first aspect in controlling ectoparasites in animals.

[0567] When used in the context of parasites inside or on the surface of an animal, the term "control" refers to reducing the number of pests or parasites, eliminating pests or parasites, and / or preventing further infestation by pests or parasites.

[0568] When used in the context of parasites inside or on the surface of an animal, the term "treatment" refers to the suppression, mitigation, cessation, or reversal of the progression or severity of existing symptoms or disease.

[0569] When used in the context of parasites inside or on the surface of an animal, the term "prevention" refers to the avoidance of the development of symptoms or disease in the animal.

[0570] When used in the context of parasites inside or on the body of an animal, the term "animal" can refer to both mammals and non-mammals, such as birds or fish. In the case of mammals, it can be either human or non-human mammals. Non-human mammals include, but are not limited to, livestock and pets. Livestock include, but are not limited to, cattle, camels, pigs, sheep, goats, and horses. Pets include, but are not limited to, dogs, cats, and rabbits.

[0571] Parasites are harmful organisms that live inside or on the surface of a host animal and benefit from it by obtaining nutrients at the expense of the host. Internal parasites are parasites that live inside the body of a host animal. External parasites are parasites that live on the surface of the body of a host animal. External parasites include, but are not limited to, ticks, insects, and crustaceans (such as sea lice). The subclass Ticks (or Acari) includes ticks and mites. Ticks include, but are not limited to, members of the following genera: *Rhipicaphalus*, such as *Rhipicaphalus microplus* (Boophilus microplus) and *Rhipicephalus sanguineus*; *Amblyomrna*; *Dermacentor*; *Haemaphysalis*; *Hyalomma*; *Ixodes*; *Rhipicentor*; *Margaropus*; *Argas*; *Otobius*; and *Ornithodoros*. Mites include, but are not limited to, members of the following genera: *Dermatophytes*, such as *Syndromea scabiei*; *Ophiopogon*, such as *Syndromea scabiei*; *Ceratophyte*; *Dermatophyte*, such as *Dermatophyte chrysalis*; *Ortnithonyssus*; *Demodex*, such as *Demodex canis*; *Scabies*, such as *Scabies mansii*; and *Scabies*. Insects include, but are not limited to, members of the following orders: *Fleas*, *Diptera*, *Liceta*, *Lepidoptera*, *Coleoptera*, and *Homoptera*. Members of the order *Fleas* include, but are not limited to, *Ctenocephatides canis* and *Ctenocephatides canis*. Members of the order *Diptera* include, but are not limited to, species of the genus *Fly*; *Dermatophytes*, such as *Hippophae rhamnoides* and *Hemiptera*; *Bubunus*, such as species of the genus *Bubunus*; *Hippophae rhamnoides*, such as *Bombyx mori*; *Stomoxys*; *Leptochloa*; midges; and mosquitoes. Members of the order Tetranychida include, but are not limited to, blood-sucking lice and chewing lice, such as the woolly lice (Bovicola ovvis) and the cow feather lice.

[0572] When used in the context of parasites inside or outside an animal, the term "effective amount" refers to the amount or dose of the compound of the present invention or a salt thereof, which, when administered to an animal in a single or multiple doses, provides the desired effect inside or outside the animal. An attending diagnostic expert (as a person skilled in the art) can readily determine the effective amount by using known techniques and by observing results obtained under similar conditions. In determining the effective amount, the attending diagnostic expert considers a number of factors, including but not limited to: the species of the mammal; its size, age, and general health status; the parasite to be controlled and the extent of infection; the specific disease or condition involved; the extent or severity of the disease or condition; the individual's response; the specific compound administered; the administration pattern; the bioavailability characteristics of the administered formulation; the selected dosing regimen; the use of concomitant drugs; and other relevant factors.

[0573] The compounds of the present invention can be administered to animals by any route with the desired effect, including but not limited to topical, oral, parenteral, and subcutaneous administration. Topical administration is preferred. Formulations suitable for topical administration include, for example, solutions, emulsions, and suspensions, and can be in the form of pouring, dotting, spraying, spray race, or dipping. Alternatively, the compounds of the present invention can be administered by ear tag or collar.

[0574] The salt forms of the compounds of the present invention include both pharmaceutically acceptable and veterinary acceptable salts, which may differ from those chemically acceptable for agricultural use. Pharmaceutically and veterinary acceptable salts and common methods for preparing them are well known in the art. See, for example, Gould, PL, “Salt selection for basic drugs”, International Journal of Pharmaceutics, 33:201-217 (1986); Bastin, RJ et al., “Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities”, Organic Process Research and Development, 4:427-435 (2000); and Berge, SM et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Sciences, 66:1-19 (1977). Those skilled in the art of synthesis will understand that, using techniques and conditions well known to those of ordinary skill in the art, the compounds of the present invention can be readily converted into salts and can be separated as salts (such as hydrochlorides). Furthermore, those skilled in the art of synthesis will understand that the compounds of the present invention can be readily converted into the corresponding free bases and can be separated from the corresponding salts as the corresponding free bases.

[0575] The present invention also provides methods for controlling pests (such as mosquitoes and other disease vectors; see also http: / / www.who.int / malaria / vector_control / irs / en / ). In one embodiment, the method for controlling pests includes applying the composition of the invention to the target pests, their location, or a surface or substrate by brushing, rolling, spraying, coating, or impregnation. By way of example, the method of the invention is contemplated for IRS (Indoor Residual Spray) application to surfaces (such as wall, ceiling, or floor surfaces). In another embodiment, the application of such compositions to substrates, such as nonwoven or woven materials, in the form of mesh fabrics, quilts, blankets, curtains, and tents (or materials that can be used in the manufacture of these articles) is contemplated.

[0576] In one embodiment, a method for controlling such pests includes applying a biocidally effective amount of the composition of the invention to the target pests, their location, or a surface or substrate to provide effective residual biocidal activity on the surface or substrate. Such application can be carried out by brushing, rolling, spraying, coating, or impregnating the biocidal composition of the invention. By way of example, the method of the invention is considered for IRS application to surfaces (such as wall, ceiling, or floor surfaces) to provide effective residual biocidal activity on the surface. In another embodiment, the application of such a composition for residual control of pests on a substrate, such as a fabric material in the form of mesh, quilts, blankets, curtains, and tents (or that can be used in the manufacture of these articles), is considered.

[0577] The substrate to be treated (including nonwovens, fabrics, or meshes) can be made of natural fibers such as cotton, raffia leaf fibers, jute, flax, sisal, burlap, or wool, or synthetic fibers such as polyamide, polyester, polypropylene, polyacrylonitrile, etc. Polyester is particularly suitable. Methods for treating textiles are known, for example, WO 2008 / 151984, WO2003 / 034823, US 5631072, WO 2005 / 64072, WO 2006 / 128870, EP 1724392, WO 2005113886, or WO 2007 / 090739.

[0578] Another application of the compositions according to the invention is in the field of tree injection / trunk treatment for all ornamental trees, as well as all kinds of fruit and nut trees.

[0579] In the field of tree injection / trunk treatment, the compounds according to the invention are particularly suitable for combating wood-boring insects from the Lepidoptera and Coleoptera mentioned above, especially those listed in Tables A and B below:

[0580] Table A. Examples of economically important invasive wood-boring insects.

[0581]

[0582] Table B. Examples of local wood-boring insects of economic importance.

[0583]

[0584]

[0585]

[0586]

[0587] This invention can also be used to control any insect pests that may be present in lawn grass, including, for example, beetles, caterpillars, fire ants, ground pearls, millipedes, sowbugs, mites, mole crickets, scale insects, mealybugs, ticks, froghoppers, southern wheat bugs, and grubs. This invention can be used to control insect pests at all stages of their life cycle, including eggs, larvae, nymphs, and adults.

[0588] Specifically, this invention can be used to control insect pests fed on the roots of lawn grasses, including grubs (such as species of the genus *Cyclocephala* spp., e.g., the marked scarab beetle, *C. lurida*), species of the genus *Rhizotrogus* (e.g., the European scarab beetle, *R. majalis*), species of the genus *Cotinus* spp. (e.g., the green June beetle, *C. nitida*), species of the genus *Popillia* spp. (e.g., the Japanese beetle, *P. japonica*), species of the genus *Phyllophaga* spp. (e.g., the May / June beetle), species of the genus *Betula* (e.g., the black turfgrass beetle, *Betula velutina*), and species of the genus *Maladera* spp. (e.g., the Asiatic garden beetle). Beetles, chestnut velvet beetles, and species of the genus Tomarus, ground pearls (species of the genus Margarodes spp.), mole crickets (brownish-yellow, southern, and short-winged; species of the genus Scapteriscus spp., African mole crickets (Gryllotalpa africana)), and leafjackets (European crane fly, species of the genus Tipula spp.).

[0589] This invention can also be used to control insect pests in lawn grasses of thatched houses, including armyworms (such as the fall armyworm Spodoptera frugiperda and the common armyworm Pseudaletia unipuncta), root cutters, weevils (species of the genus Sphenophorus, such as S. venatus verstitus and S. parvulus), and grass moths (such as species of the genus Crambus and the tropical grass moth Herpetogramma phaeopteralis).

[0590] This invention can also be used to control insect pests in turfgrass that live on the ground and feed on the leaves of turfgrass, including wheat bugs (such as southern wheat bugs and southern stem bugs (Blissus insularis)), bermudagrass mite (Eriophyes cynodoniensis), grass mealybug (Antonina graminis)), two-lined grasshopper (Propsapia bicincta), leafhoppers, root-cutting moths (Noctuidae), and wheat aphid.

[0591] This invention can also be used to control other harmful organisms in lawn grasses, such as introduced red imported fire ants (Solenopsis invicta) that create nests in lawns.

[0592] In the field of hygiene, the compositions according to the present invention are effective against antiparasitic parasites such as hard ticks, soft ticks, scabies mites, fall mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.

[0593] Examples of this type of parasite are:

[0594] Lice: Species of the genera *Linognathus*, *Phtirus*, *Phtirus*, and *Phtirus*.

[0595] Trichophagia: Species of the genera *Felicolas*, *Felicola*, *Felicola*, *Felicola*, *Felicola*, *Felicola*, *Felicola*, *Felicola*, *Felicola*, *Felicola*, and *Felicola*.

[0596] Diptera and the suborders Nematocerina and Brachycerina, such as species of the genera *Aedes*, *Anopheles*, *Culex*, *Simulium*, *Eusimulium*, *Phlebotomus*, *Lutzomyia*, *Culicoides*, *Chrysops*, *Hybomitra*, *Atylotus*, *Tabanus*, *Haematopota*, *Philipomyia*, and *Braula*. spp.), *Musca* spp., *Hydrotaea* spp., *Haematobias* spp., *Morellia* spp., *Fannia* spp., *Glossina* spp., *Calliphora* spp., *Lucilia* spp., *Chrysomyia* spp., *Wohlfahrtia* spp., *Sarcophaga* spp., *Oestrus* spp., *Hypoderma* spp., *Gasterophilus* spp., *Hippobosca* spp., *Lipoptena* spp. spp.) and species of the genus Melophagos (Melophagus spp.).

[0597] Siphonapterida, including species of the genera *Pulex*, *Xenopsylla*, and *Xenopsylla*.

[0598] Heteropterida, including species of the genera *Pycnodon*, *Triatomine*, *Aspergillus*, and *Panstrongylus* spp.

[0599] Blattodea, including species such as the Oriental cockroach (Blatta orientalis), the American cockroach (Periplaneta americana), the German cockroach (Blattelagermanica), and species of the genus Supella (Supella spp.).

[0600] Acaria (subclass Acaria, family Acarida), and the orders Metastigmata and Mesostigmata, including species of the genera *Argas*, *Ornithodorus*, *Otobius*, *Ixodes*, *Amblyommas*, *Boophilus*, *Dermacentor*, *Haemophysalis*, *Hyalomma*, *Rhipicephalus*, *Dermanyssus*, *Raillietia*, and *Pneumonyssus*. spp.), species of the genus *Sternostoma* spp., and species of the genus *Varroaspp.*.

[0601] Actinedida (prostigmata) and Acaridida (Astigmata), including species of the genera *Acarapis*, *Cheyletiella*, *Ornithocheyletia*, *Myobia*, *Psorergates*, *Demodex*, *Trombicula*, *Listrophorus*, *Acarus*, *Tyrophagus*, *Caloglyphus*, *Hypodectes*, and *Pterolichus*. Species of the genera *Psoroptes*, *Chorioptes*, *Otodectes*, *Sarcoptes*, *Notoedress*, *Knemidocoptes*, *Cytodites*, and *Laminosioptes*.

[0602] The compositions according to the invention are also suitable for protecting materials such as wood, textiles, plastics, adhesives, glues, paints, paper and cards, leather, flooring and buildings from insect infestation.

[0603] The compositions according to the invention can be used, for example, to combat the following pests: beetles, such as the North American house longhorn beetle, long-haired longhorn beetle, furniture borer, red-haired borer, comb-horned vein borer, Dendrobium pertinex, pine bud twig borer, Priobium carpini, brown powdery beetle, African powdery beetle, southern powdery beetle, oak powdery beetle, pubescent powdery beetle, breast powdery beetle, scale powdery beetle, species of the genus *Bark beetle*, species of the genus *Bark beetle*, coffee black longhorn beetle, oak longhorn beetle, brown heteroptera longhorn beetle, species of the genus *Dyssula*, and bamboo longhorn beetle; and also hymenoptera, such as the blue-black tree beetle, the large tree beetle, the thiaga tree beetle, and *Urocerus augur*; and termites, such as the European wood termite (*Kalotermes*). (flaviccollis), *Reticulitermes maculatus*, *Reticulitermes spp. ...

[0604] Compounds having formulas I and I'a, or salts thereof, are particularly suitable for controlling one or more pests selected from the following families: Noctuidae, Pyrenidae, Chrysophagidae, Thrips, Stink Bugs, Toxascaridae, Planthoppers, Aphids, Noctuidae, Pyralidae, Root-knot Nematodes, and Heterodermidae. In a preferred embodiment of each aspect, compound TX (wherein the abbreviation "TX" means "a compound selected from the compounds defined in Tables D-1 to D-66 and Table P") controls one or more pests selected from the following families: Noctuidae, Pyrenidae, Chrysophagidae, Thrips, Stink Bugs, Toxascaridae, Planthoppers, Aphids, Noctuidae, Pyralidae, Root-knot Nematodes, and Heterodermidae.

[0605] Compounds having formulas I and I'a, or salts thereof, are particularly suitable for controlling one or more pests selected from the genera *Gnaphalium*, *Plutella*, *Thrips*, *Plutella*, *Cydia*, *Rhizoctonia*, *Aphidius*, *Aphidius*, *Leymus*, *Aphidius*, *Gnaphalium*, *Gnaphalium*, and *Gnaphalium*. In a preferred embodiment of each aspect, compound TX (wherein the abbreviation "TX" means "a compound selected from the compounds defined in Tables D-1 to D-66 and Table P") controls one or more pests selected from the genera *Gnaphalium*, *Plutella*, *Thrips*, *Plutella*, *Cydia*, *Rhizoctonia*, *Aphidius*, *Aphidius*, *Leymus*, *Aphidius*, *Gnaphalium*, and *Gnaphalium*.

[0606] Compounds having formulas I and I'a or their salts are particularly suitable for controlling one or more of the following: sea grebe moth, diamondback moth, western flower thrips, tobacco thrips, hero American bug, codling moth, brown rice leafhopper, peach aphid, soybean looper, soybean aphid, cucumber leaf beetle, cereal constrictor aphid, and rice stem borer.

[0607] In preferred embodiments of each aspect, compound TX (wherein the abbreviation "TX" means "a compound selected from the compounds defined in Tables D-1 to D-66 and Table P") controls one or more of the following: sea nymph, diamondback moth, western flower thrips, tobacco thrips, American stink bug, codling moth, brown rice leafhopper, peach aphid, soybean looper, soybean aphid, cucumber leaf beetle, cereal constrictor aphid, and rice stem borer, such as sea nymph + TX, diamondback moth + TX, western flower thrips + TX, tobacco thrips + TX, American stink bug + TX, codling moth + TX, brown rice leaf beetle + TX, peach aphid + TX, soybean looper + TX, soybean aphid + TX, cucumber leaf beetle + TX, cereal constrictor aphid + TX, and rice stem borer + TX.

[0608] In each embodiment, a compound from Tables D-1 to D-66 and Table P is suitable for controlling the following pests on cotton, vegetables, corn, cereals, rice, and soybean crops: sea grebe moth, diamondback moth, western flower thrips, tobacco thrips, hero American bug, codling moth, brown rice leafhopper, peach aphid, soybean looper, soybean aphid, cucumber leaf beetle, cereal constrictor aphid, and rice stem borer.

[0609] In the embodiments, a compound from Tables D-1 to D-66 and Table P is suitable for controlling the cabbage looper (Mamestra) (preferably on vegetables), the codling moth (preferably on apples), the small green leafhopper (Empoasca) (preferably on vegetables and vineyards), the potato leaf beetle (Leptinotarsa) (preferably on potatoes), and the rice stem borer (preferably on rice).

[0610] Compounds according to the invention can possess any number of benefits, particularly including favorable levels of bioactivity for protecting plants against insects or superior properties for use as active ingredients in agrochemicals (e.g., higher bioactivity, favorable activity spectrum, increased safety (against non-target organisms such as fish, birds, and bees) both above and below ground), improved physicochemical properties, or increased biodegradability). Specifically, it has been unexpectedly found that certain compounds having Formula I can exhibit favorable safety relative to non-target arthropods, particularly pollinators (such as honeybees, solitary bees, and bumblebees). Most particularly, relative to the Italian bee (Apis mellifera).

[0611] The compounds according to the invention can be used as pest control agents in their unmodified form, but they are generally formulated into compositions in a variety of ways using formulation aids (such as carriers, solvents, and surfactants). These formulations can be in various physical forms, for example, as powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, flowable oils, aqueous dispersions, oily dispersions, suspensions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or water-miscible organic solvents as carriers), impregnated polymer films, or in other known forms, such as those described in the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, 1st Edition, Second Revision (2010). Such formulations can be used directly or diluted before use. It can be diluted with, for example, water, liquid fertilizer, micronutrients, biological organisms, oil or solvents.

[0612] These formulations can be prepared, for example, by mixing the active ingredients with formulation aids to obtain compositions in the form of finely dispersed solids, particles, solutions, dispersions, or emulsions. These active ingredients can also be formulated with other aids, such as finely dispersed solids, mineral oils, oils of plant or animal origin, modified oils of plant or animal origin, organic solvents, water, surfactants, or combinations thereof.

[0613] These active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredient within a porous carrier. This allows the active ingredient to be released into the environment in a controlled amount (e.g., slow release). Microcapsules typically have a diameter from 0.1 to 500 micrometers. The amount of active ingredient they contain is approximately 25% to 95% by weight of the capsule. These active ingredients can be in the form of a monolithic solid, fine particles in a solid or liquid dispersion, or in a solution-suitable form. The encapsulating membrane can comprise, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymers, polyacrylonitrile, polyacrylates, polyesters, polyamides, polyureas, polyurethanes, or chemically modified polymers, as well as starch xanthates, or other polymers known to those skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely dispersed particles within a solid matrix of the base material, but these microcapsules themselves are not encapsulated.

[0614] Suitable formulation aids for preparing compositions according to the invention are known in themselves. As liquid carriers, the following can be used: water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butenyl carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol, 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, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glyceryl acetate, glyceryl diacetate, glyceryl triacetate, deca-acetate, etc. Hexadecane, hexanediol, isopentyl 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, octadecanoic acid, octylamine acetate, oleic acid, oleyleneamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate Propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols with higher molecular weights, such as pentanol, tetrahydrofuranol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, etc.

[0615] Suitable solid carriers include, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin, and similar substances.

[0616] Many surfactants can be advantageously used in both solid and liquid formulations, especially those that can be diluted with a carrier before use. Surfactants can be anionic, cationic, nonionic, or polymeric, and they can be used as emulsifiers, wetting agents, suspending agents, or for other purposes. Typical surfactants include, for example, salts of alkyl sulfates, such as diethanolammonium dodecyl sulfate; salts of alkyl aryl sulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol / olefin oxide addition products, such as ethoxylated nonylphenol; alcohol / olefin oxide addition products, such as ethoxylated tridecyl alcohol; soaps, such as sodium stearate; salts of 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 compounds, such as dodecyltrimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of monoalkyl and dialkyl phosphate esters; and other substances, such as those described in McCutcheon's Detergents and Emulsifiers Annual, MC Publishing. Corp.), Ridgewood, New Jersey (1981).

[0617] Other adjuvants that can be used in formulations for killing pests include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, substances that neutralize or change pH and buffer solutions, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, flow aids, lubricants, dispersants, thickeners, antifreeze agents, microbial agents, and liquid and solid fertilizers.

[0618] The compositions according to the invention may include additives comprising oils of plant or animal origin, mineral oils, alkyl esters of such oils, or mixtures of such oils with oil derivatives. The amount of oil additive in the compositions according to the invention is typically from 0.01% to 10% of the mixture to be applied. For example, the oil additive may be added to the spray can at the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral oils or plant-derived oils, such as rapeseed oil, olive oil, or sunflower oil; emulsified vegetable oils; alkyl esters of plant-derived oils, such as methyl derivatives; or animal-derived oils, such as fish oil or tallow. Preferred oil additives include C8-C... 22 Alkyl esters of fatty acids, especially C 12 -C 18Methyl derivatives of fatty acids, such as lauric acid, palmitic acid, and methyl esters of oleic acid (methyl laurate, methyl palmitate, and methyl oleate, respectively). Many oil derivatives are known in the Compendium of Herbicide Adjuvants, 10th edition, Southern Illinois University, 2010.

[0619] These compositions of the invention generally comprise from 0.1% to 99%, particularly from 0.1% to 95% by weight, of the compounds of the invention and from 1% to 99.9% by weight, of formulation aids, which preferably comprise from 0% to 25% by weight of surfactants. Commercial products may preferably be formulated as concentrates, while end users will typically use diluted formulations.

[0620] Application rates vary over a wide range and depend on soil properties, application method, crop species, 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.

[0621] Preferred formulations may have the following composition (wt%):

[0622] Emulsifiable concentrate :

[0623] Active ingredient: 1% to 95%, preferably 60% to 90%

[0624] Surfactant: 1% to 30%, preferably 5% to 20%

[0625] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0626] dust :

[0627] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%.

[0628] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%.

[0629] Suspension concentrate:

[0630] Active ingredient: 5% to 75%, preferably 10% to 50%

[0631] Water: 94% to 24%, preferably 88% to 30%

[0632] Surfactant: 1% to 40%, preferably 2% to 30%

[0633] wettable powder :

[0634] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0635] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0636] Solid carrier: 5% to 95%, preferably 15% to 90%

[0637] Granules:

[0638] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%

[0639] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0640] The following examples further illustrate (but do not limit) the invention.

[0641] <![CDATA[ wettable powder ]]> a) b) c) Active ingredient 25％ 50％ 75％ Sodium lignosulfonate 5％ 5％ - Sodium lauryl sulfate 3％ - 5％ Sodium diisobutylnaphthalenesulfonate - 6％ 10％ Phenolic polyethylene glycol ether (7-8 mol of ethylene oxide) - 2％ - Highly dispersed silica 5％ 10％ 10％ Kaolin 62％ 27％ -

[0642] The combination is thoroughly mixed with these adjuvants and the mixture is thoroughly ground in a suitable grinder to obtain a wettable powder that can be diluted with water to give a suspension of the desired concentration.

[0643] <![CDATA[ Powder for dry seed treatment ]]> a) b) c) Active ingredient 25％ 50％ 75％ Light mineral oil 5％ 5％ 5％ Highly dispersed silica 5％ 5％ - Kaolin 65％ 40％ - talc - 20％

[0644] The combination is thoroughly mixed with the adjuvant and the mixture is thoroughly ground in a suitable grinder to obtain a powder that can be used directly for seed treatment.

[0645] <![CDATA[ Emulsifiable concentrate ]]> Active ingredient 10％ Octylphenol polyethylene glycol ether (4-5 mol of ethylene oxide) 3％ Calcium dodecylbenzenesulfonate 3％ Castor oil polyethylene glycol ether (35 mol ethylene oxide) 4％ Cyclohexanone 30％ xylene mixture 50％

[0646] Emulsions with any required dilution that can be used in plant protection can be obtained by diluting such concentrates with water.

[0647] <![CDATA[ dust ]]> a) b) c) Active ingredient 5％ 6％ 4％ talc 95％ - - Kaolin - 94％ - Mineral packing - - 96％

[0648] A ready-to-use dust is obtained by mixing the mixture with a carrier and grinding the mixture in a suitable grinder. This type of powder can also be used for dry seed dressing.

[0649] <![CDATA[ Extruder Particles ]]> Active ingredient 15％ Sodium lignosulfonate 2％ Carboxymethyl cellulose 1％ Kaolin 82％

[0650] 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.

[0651] <![CDATA[ Coated particles ]]> Active ingredient 8％ Polyethylene glycol (molecular weight 200) 3％ Kaolin 89％

[0652] This finely ground mixture is applied evenly to kaolin moistened with polyethylene glycol in a mixer. This process yields dust-free coated particles.

[0653] suspension concentrate

[0654] Active ingredient 40％ Propylene glycol 10％ Nonylphenol polyethylene glycol ether (15 mol ethylene oxide) 6％ Sodium lignosulfonate 10％ Carboxymethyl cellulose 1％ Silicone oil (in the form of a 75% emulsion in water) 1％ water 32％

[0655] The finely ground mixture is tightly blended with 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 dilutions, living plants along with their propagation material can be treated and protected against microbial infections by spraying, watering, or immersion.

[0656] Flowable concentrate for seed treatment

[0657]

[0658]

[0659] The finely ground mixture is tightly blended with 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 dilutions, living plants along with their propagation material can be treated and protected against microbial infections by spraying, watering, or immersion.

[0660] Sustained-release capsule suspension

[0661] 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 purpose.

[0662] 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.

[0663] Preparation example:

[0664] L CMS method:

[0665] Method 1:

[0666] Spectra were recorded on a mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) from Waters Corporation, which is 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 Da 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.

[0667] Method 2:

[0668] Spectra were recorded on a mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) from Waters Corporation, which is equipped with an electro-jet source (polarity: positive and negative ions, capillary: 3.00 kV, cone range: 41 V, extractor: 2.00 V, source temperature: 150 °C, desolvation temperature: 5000 °C, cone gas flow rate: 50 L / h, desolvation gas flow rate: 1000 L / h, mass range: 110 Da to 800 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: 40 °C, PDA wavelength range (nm): 200 to 400, solvent gradient: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; gradient: 10%-100% B, over 1.3 min; flow rate (ml / min): 0.6.

[0669] Method 3:

[0670] Spectra were recorded on a mass spectrometer (SQD, SQDII, or QDA single quadrupole mass spectrometer) from Waters Corporation, equipped with an electro-ejector source (polarity: positive and negative ions, capillary: 0.8–3.00 kV, cone: 5–30 V, source temperature: 120–150 °C, desolvation temperature: 350–600 °C, cone gas flow rate: 50–150 L / h, desolvation gas flow rate: 650–1000 L / h, mass range: 50 Da to 900 Da), and an Acquity UPLC from Waters Corporation: a binary pump, a heated column chamber, a diode array detector, and an ELSD. Column: Waters UPLC HSST3, 1.8 μm, 30 × 2.1 mm, temperature: 60 °C, DAD wavelength range (nm): 210 to 400, run time: 1.5 min; solvent: A = water + 5% MeOH + 0.05% HCOOH, B = acetonitrile + 0.05% HCOOH; flow rate (ml / min): 0.85, gradient: 10% B isocratic for 0.2 min, then 10%-100% B, 100% B isocratic for 0.2 min over 1.0 min, then 100%-10% B, 10% B isocratic for 0.05 min over 0.05 min.

[0671] Method 4:

[0672] Spectra were recorded on a Waters mass spectrometer (SQD, SQDII, or QDA single quadrupole mass spectrometer) equipped with an electro-jet source (polarity: positive and negative ions, capillary: 3.00 kV, cone: 41 V, source temperature: 150 °C, desolvation temperature: 500 °C, cone gas flow rate: 50 L / h, desolvation gas flow rate: 1000 L / h, mass range: 110 Da to 800 Da), and a Waters Acquity UPLC: binary pump, heated column chamber, diode array detector, and ELSD. Column: Waters UPLC HSS T3, 1.8 μm, 30 × 2.1 mm, temperature: 40 °C, DAD wavelength range (nm): 200 to 400, run time: 1.6 min; solvent: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.05% HCOOH; flow rate (ml / min): 0.6, gradient: 10%-50% B in 0.2 min, then 50%-100% B in 0.5 min, 100% B isocratic for 0.6 min, 100%-10% B in 0.05 min, 100% to 10% B in 0.1 min, then 10% B isocratic for 0.2 min.

[0673] Method 5:

[0674] Spectra were recorded on a mass spectrometer (SQD, SQDII, or QDA single quadrupole mass spectrometer) from Agilent Technologies, equipped with an electrospray source (polarity: positive and negative ions, capillary: 4.00 kV, fragmentation voltage: 100 V, gas temperature (°C): 350, gas flow rate: 11 L / min, mass range: 110 to 1000 Da) and an Agilent HPLC from Agilent Technologies: column: KINETEX EVO C18, 2.6μm, 50×4.6mm, temperature: 40℃, DAD wavelength range (nm): 210 to 400, run time: 2.5min; solvent: A = water + 5% acetonitrile + 0.1% HCOOH, B = acetonitrile + 0.1% HCOOH; flow rate (ml / min): 1.8, gradient: 10%-100% B within 0.9min, 100% B isocratic for 0.9min, 100%-10% B within 0.4min, 10% B isocratic for 0.3min.

[0675] Example 1: N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline Preparation of lino-4-amine (compound P.5)

[0676]

[0677] Step A: 5-[[2,4-bis(trifluoromethyl)aniline]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione Preparation of (Intermediate I-1)

[0678]

[0679] 2,2-Dimethyl-1,3-dioxane-4,6-dione (3.46 g, 24 mmol, 1.2 equivalents) and trimethoxymethane (11 mL, 96 mmol, 4.8 equivalents) were heated to reflux for 90 min. Next, 2,4-bis(trifluoromethyl)aniline (4.72 g, 20 mmol, 1 equivalent) was added at the same temperature, and the solution was stirred for 50 min. Stirring and heating were stopped, and a solid began to precipitate. The solid was collected at room temperature, washed with cyclohexane, and air-dried. A second batch of solid could be collected from the filtrate and washed with cyclohexane. Product I-1 (6.27 g, 82%) was given as a grayish-white solid.

[0680] 1 H NMR (400MHz, CDCl3) δppm: 1.80 (s, 6H), 7.64 (d, J = 8.80Hz, 1H), 7.96 (d, J = 8.44Hz, 1H), 7.98-8.03 (m, 1H), 8.67 (d, J = 13.20Hz, 1H), 11.87 (br d,J=12.84Hz,1H).

[0681] Step B: Preparation of 6,8-bis(trifluoromethyl)-1H-quinoline-4-one (intermediate I-2)

[0682]

[0683] 5-[[2,4-bis(trifluoromethyl)aniline]methylene]-2,2-dimethyl-1,3-dioxane-4,6-dione (I-1, 3.12 g, 8.14 mmol) was added to diphenyl ether (15 mL) under reflux. The mixture was stirred under reflux for 30 minutes and then allowed to cool to room temperature. The reaction mixture was diluted with cyclohexane (20 mL), and the precipitate was filtered and washed with a large amount of cyclohexane. The desired product (1.63 g, 71%) was obtained as a light brown powder.

[0684] 1 H NMR (400MHz, DMSO-d6) δppm: 6.33 (br s, 1H), 7.97 (br s, 1H), 8.33 (s, 1H), 8.66 (br s, 1H), 11.57 (br s, 1H).

[0685] LC-MS (Method 3): Retention time 0.86 min, m / z 282 [M+H] + ].

[0686] Step C: 4-Chloro-6,8-bis( Preparation of trifluoromethyl)quinoline (intermediate I-3)

[0687]

[0688] Phosphorus oxychloride (3 mL, 31.5 mmol, 3.21 equivalence) was added to a flask containing 6,8-bis(trifluoromethyl)-1H-quinoline-4-one (I-3, 2.76 g, 9.81 mmol) and the mixture was stirred at 100 °C for 15 min, then cooled to room temperature and placed in an ice bath. The reaction was quenched with water and ammonia was added until the pH reached 8–9. The mixture was then extracted three times with dichloromethane (3 x 100 mL) and concentrated under reduced pressure to provide the desired product (2.5 g, 8.3 mmol, 85%) as a light brown powder.

[0689] 1 H NMR (400MHz, CDCl3) δppm: 7.75 (d, J = 4.77Hz, 1H), 8.34 (s, 1H), 8.82 (s, 1H), 9.08 (d, J = 4.77Hz, 1H).

[0690] LC-MS (Method 3): Retention time 1.18 min, m / z 300 [M+H] + ].

[0691] Step D: Preparation of (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolinyl]amino]propionamide (intermediate I-4)

[0692]

[0693] To 4-chloro-6,8-bis(trifluoromethyl)quinoline (I-3, 1.51 g, 5.04 mmol), (2S)-2-aminopropionamide hydrochloride (3.24 g, 25.2 mmol, 5.00 equivalents) and potassium carbonate (4.88 g, 35.3 mmol, 7 equivalents) were added to N,N-dimethylformamide (50 mL). The reaction mixture was heated to 100 °C overnight. The reaction mixture was cooled, diluted with water, and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (541 mg, 31% yield) as a brown solid.

[0694] 1H NMR (400MHz, DMSO-d6) δppm: 1.49-1.58(m,3H),4.09-4.19(m,1H),6.49-6.55(m,1H),7.13-7.22(m, 1H),7.63-7.71(m,1H),7.83-7.90(m,1H),8.17-8.24(m,1H),8.60-8.66(m,1H),9.23-9.29(m,1H).

[0695] LC-MS (Method 3): Retention time 0.75 min, m / z 352 [M+H] + ].

[0696] Step E: (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolinyl]amino]-N-(dimethylaminomethylene)propane Preparation of amide (compound I-5)

[0697]

[0698] To a solution of (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolinyl]amino]propionamide (I-4, 0.74 g, 2.1 mmol) in 2-methyltetrahydrofuran (21 mL), 1,1-dimethoxy-N,N-dimethyl-methylamine (0.56 mL, 4.2 mmol, 2 equivalents) was added and the reaction mixture was stirred at 50 °C for 30 min. The reaction was cooled and concentrated under reduced pressure to provide (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolinyl]amino]-N-(dimethylaminomethylene)propionamide (I-5) (755 mg, 80%) as a brown solid.

[0699] 1 H NMR (400MHz, DMSO-d6) δppm: 1.57 (d, J = 6.97Hz, 3H), 2.98-3.09 (m, 3H), 3.10-3.19 (m, 3H), 4.22-4.37 (m, 1H), 6. 45-6.55(m,1H),7.83-7.94(m,1H),8.17-8.25(m,1H),8.43-8.52(m,1H),8.52-8.60(m,1H),9.20-9.31(m,1H).

[0700] Step F: N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline Preparation of lino-4-amine (compound P.5)

[0701]

[0702] (2S)-2-[[6,8-bis(trifluoromethyl)-4-quinolinyl]amino]-N-(dimethylaminomethylene)acrylamide (I-5 prepared above, 755 mg, 1.86 mmol, 1 equivalent)) was dissolved in 2-methyltetrahydrofuran (7.4 mL). Next, pyrimidin-2-ylhydrazine hydrochloride (0.49 g, 3.35 mmol) and acetic acid (4.65 mL) were added, and the reaction was stirred at 80 °C for 1 hour. The reaction was cooled, diluted with ethyl acetate, and extracted with water. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (P.5) as a light brown solid (631.5 mg, 75% yield).

[0703] 1 H NMR (400MHz, DMSO-d6) δppm: 1.76 (d, J = 6.97Hz, 3H), 5.96 (quin, J = 7.06Hz, 1H), 6.60 (d, J = 5.87Hz, 1H), 7.51-7.6 2(m,1H),8.15-8.22(m,2H),8.26(d,J=7.34Hz,1H),8.55(d,J=5.50Hz,1H),8.92(d,J=5.14Hz,2H),9.14(s,1H).

[0704] LC-MS (Method 3): Retention time 0.88 min, m / z 455 [M+H] + ].

[0705] Example 2: N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin- Preparation of 4-amine (compound P.16)

[0706]

[0707] Step A: Preparation of 2-iodo-4,6-bis(trifluoromethyl)aniline (intermediate I-6)

[0708]

[0709] 2,4-Bis(trifluoromethyl)aniline (CAS No. 367-71-5, 1.50 g, 6.2 mmol) was dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol and the solution was cooled to 0 °C. N-iodosuccinimide (1.47 g, 6.2 mmol, 1 equivalent) was added, and the reaction was stirred at 0 °C for 1 h, and then stirred overnight at room temperature. The reactants were concentrated under reduced pressure, and the crude material was purified by rapid silica gel chromatography (ethyl acetate in cyclohexane) to obtain the product (I-6) (2.09 g, 95%) as a light pink crystalline solid.

[0710] 1H NMR (400MHz, CDCl3) δppm: 5.08 (br s, 2H), 7.70-7.74 (m, 1H), 8.06 (d, J = 1.47Hz, 1H).

[0711] Step B: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzonitrile (intermediate I-7)

[0712]

[0713] 2-Iodo-4,6-bis(trifluoromethyl)aniline (I-6, 1.00 g, 2.82 mmol), N,N-dimethylformamide (5.63 mL), and copper cyanide (I) (0.31 g, 3.38 mmol, 1.2 equivalents) were charged into a sealed tube. The mixture was stirred overnight at 100 °C. The mixture was cooled, filtered through diatomaceous earth, and extracted twice with MTBE (2 x 20 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under vacuum. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (I-7) (567 mg, 79%) as a brown solid.

[0714] 1 H NMR (400MHz, CDCl3) δppm: 5.33 (br s, 2H), 7.83-7.90 (m, 2H).

[0715] 19 F NMR (377MHz, CDCl3) δppm: -63.94 (s, 1F), -62.19 (s, 1F).

[0716] LC-MS (Method 3): Retention time 1.01 min, m / z 253 [MH] - ].

[0717] Step C: Preparation of 6,8-bis(trifluoromethyl)quinazolin-4-ol (intermediate I-8)

[0718]

[0719] 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (I-7, 8.8 g, 35 mmol), formic acid (83 mL), and sulfuric acid (2.8 mL, 52 mmol, 1.5 equivalents) were added to a flask and the mixture was stirred at 50 °C for 3 hours. The reaction mixture was then cooled to room temperature and slowly poured into 300 mL of ice water while stirring for 15 minutes. The resulting solid was filtered off and dried to give the desired product (I-8) (8.9 g, 91%) as a grayish-white solid.

[0720] 1 H NMR (400MHz, DMSO-d6) δppm: 1¹H NMR (400MHz, solvent) δppm 8.31-8.47 (m, 2H), 8.61 (s, 1H), 12.97 (br s, 1H).

[0721] LC-MS (Method 3): Retention time 0.90 min, m / z 283 [M+H] + ].

[0722] Step D: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinazoline (intermediate I-9)

[0723]

[0724] Five drops of N,N-dimethylformamide were added to a solution of 6,8-bis(trifluoromethyl)quinazolin-4-ol (I-8, 0.5 g, 5.04 mmol) in thionyl chloride (8.87 mL). The reaction mixture was heated to 100 °C for 1 hour until the reaction became homogeneous. The reaction was cooled and concentrated under reduced pressure to provide the desired product (I-9), which was used as is in the next step.

[0725] 1 H NMR (400MHz, CDCl3) δppm: 8.50 (s, 1H), 8.84 (s, 1H), 9.33 (s, 1H).

[0726] 19 F NMR (377MHz, CDCl3) δppm: -62.86 (s, 1F), -60.78 (s, 1F).

[0727] LC-MS (Method 3): Retention time 0.75 min, m / z 352 [M+H] + ].

[0728] Step E: N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin- Preparation of 4-amine (compound P.16)

[0729]

[0730] A flask was charged with 4-chloro-6,8-bis(trifluoromethyl)quinazoline (I-9, 200 mg, 0.67 mmol), 1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylammonium chloride (prepared as in WO2019 / 197468) (201 mg, 0.80 mmol, 1.2 equivalents), potassium carbonate (276 mg, 2.0 mmol, 3 equivalents), and acetonitrile (3 mL), and heated at 80 °C for 4 hours. The reaction was cooled, the salt was removed by filtration, and the resulting crude product was concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (P.16) as a pale yellow solid (120 mg, 40% yield).

[0731] 1 H NMR (400MHz, CDCl3) δppm: 1.85 (d, J = 6.97Hz, 3H), 6.71 (quin, J = 6.97Hz, 1H), 7.49 (t, J = 4.77Hz, 1H), 8.14 (s, 1H), 8.16 (s, 1H), 8.27 (br d,J=4.03Hz,1H),8.38(s,1H),8.68(s,1H),9.01(d,J=4.77Hz,2H).

[0732] LC-MS (Method 3): Retention time 0.97 min, m / z 455 [M+H] + ].

[0733] Example 3: 2-Chloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline Preparation of zoline-4-amine (compound P.25)

[0734]

[0735] Step A: Preparation of 6,8-bis(trifluoromethyl)quinazoline-2,4-diol (intermediate I-10)

[0736]

[0737] 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2, 2 g, 7.87 mmol) and dichloromethane (20 mL) were added to a flask. Chlorosulfonyl isocyanate (0.85 mL, 9.44 mmol, 1.2 equivalents) was added to the mixture, and the mixture was stirred for 3 hours. The reaction was concentrated under reduced pressure, and the residue was heated in water (50 mL) at 100 °C for 18 hours. The resulting white solid was separated by filtration to provide the desired product (I-10) (800 mg, 34%).

[0738] 1 H NMR (400MHz, CD3CN) δppm: 8.20-8.23 (m, 1H), 8.50 (s, 1H), 8.73 (br s, 1H), 9.51 (br s, 1H).

[0739] Step B: Preparation of 2,4-dichloro-6,8-bis(trifluoromethyl)quinazoline (intermediate I-11)

[0740]

[0741] 6,8-bis(trifluoromethyl)quinazoline-2,4-diol (I-10, 100 mg, 0.34 mmol) and phosphorus oxychloride (0.32 mL, 3.4 mmol, 10 equivalents) were added to a flask. N,N-diisopropylethylamine (0.118 mL, 0.67 mmol, 2 equivalents) was then added to the mixture, and the resulting mixture was heated at 100 °C for 2 hours. The reaction was concentrated under reduced pressure, and the crude material was rapidly purified by silica gel chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-11) (84 mg, 75%) as a grayish-white solid.

[0742] 1 H NMR (400MHz, CD3CN) δppm: 8.66 (s, 1H), 8.90 (s, 1H).

[0743] Step C: 2-Chloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline Preparation of zoline-4-amine (compound P.25)

[0744]

[0745] A flask was charged with 2,4-dichloro-6,8-bis(trifluoromethyl)quinazoline (I-11, 100 mg, 0.30 mmol), 1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylammonium chloride (prepared as in WO2019 / 197468) (68 mg, 0.27 mmol, 0.9 equivalent), potassium carbonate (123 mg, 0.90 mmol, 3 equivalent), and acetonitrile (1.5 mL) and heated at 80 °C for 16 hours. The reaction was cooled, diluted with water, and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (P.25) as a pale yellow solid (60 mg, 41% yield).

[0746] 1 H NMR (400MHz, DMSO-d6) δppm: 1.79 (d, J = 6.72Hz, 3H) 6.38 (t, J = 6.72Hz, 1H) 7.65 (t, J = 4.65Hz, 1H) 8.18 (s, 1H) 8.37 (br s,1H)8.99(d,J=4.65Hz,2H)9.24(br s,1H)9.90(br d,J=6.36Hz,1H).

[0747] LC-MS (Method 4): Retention time 1.09 min, m / z 489 [M+H] + ].

[0748] Example 4: N-methyl-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl) Preparation of quinazoline-4-amine (compound P.27)

[0749]

[0750] N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinazolin-4-amine (P.16 prepared in Example 2, 148 mg, 0.33 mmol), cesium carbonate (319 mg, 0.98 mmol, 3 equivalents), acetonitrile (1.3 mL), and methyl iodoforme (0.041 mL, 0.65 mmol, 2 equivalents) were added to a flask. The mixture was heated at 50 °C overnight. The reaction was cooled and diluted with water (10 mL). The mixture was extracted three times with ethyl acetate (3 x 10 mL), and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (P.27) (92 mg, 60%).

[0751] 1 H NMR (400MHz, CDCl3) δppm: 1.98 (d, J=6.97Hz, 3H), 3.37 (s, 3H), 6.89 (q, J=6.97Hz, 1H), 7.23 (t,J=4.95Hz,1H),8.11(s,1H),8.24(d,J=6.60Hz,2H),8.57(d,J=4.77Hz,2H),8.60(s,1H).

[0752] LC-MS (Method 3): Retention time 0.97 min, m / z 455 [M+H] + ].

[0753] 19 F NMR (376MHz, CDCl3) δppm: -62.40 (s, 1F), -61.33 (s, 1F).

[0754] LC-MS (Method 3): Retention time 1.01 min, m / z 469 [M+H] + ].

[0755] Example 5 : 8-chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl) [Ethyl]-6-(trifluoromethyl)quinazolin-4-amine (compound P.36)

[0756]

[0757] Step A: 8-Chloro-4-[cyclopropylmethyl-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]amino]- Preparation of 6-(trifluoromethyl)-1H-quinazolin-2-one (intermediate I-12)

[0758]

[0759] 2,8-Dichloro-N-(cyclopropylmethyl)-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6-(trifluoromethyl)quinazoline-4-amine (similar to P.49 prepared in Example 3, P.25, 180 mg, 0.35 mmol) and acetic acid (1.8 mL) were added to a flask. The mixture was stirred at 80 °C for 2 hours. The reaction was concentrated under reduced pressure, and the residue was purified by reversed-phase chromatography (acetonitrile in water) to provide the desired product (I-12) (90 mg, 52%).

[0760] 1 H NMR (400MHz, DMSO-d6) δppm:0.02-0.07(m,1H),0.09-0.16(m,1H),0.25-0.32(m,1H),0.35-0.41(m,1H),0.77-0.85(m,1H),1.87(d,3H) ,3.06(dd,1H),3.36(dd,1H),6.40-6.46(m,1H),7.38(t,1H),7.69(s,1H),8.19(s,1H),8.25(s,1H),8.54(d,2H),10.84-10.92(m,1H).

[0761] Step B: 8-Chloro-N-(cyclopropylmethyl)-2-methoxy-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl) Preparation of ethyl]-6-(trifluoromethyl)quinazolin-4-amine (compound P.36)

[0762]

[0763] 8-Chloro-4-[cyclopropylmethyl-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]amino]-6-(trifluoromethyl)-1H-quinazolin-2-one (I-12, 35 mg, 0.07 mmol) was dissolved in acetonitrile (0.53 mL) and potassium carbonate (30 mg, 0.21 mmol, 3 equivalents), followed by the addition of dimethyl sulfate (7.5 μL, 0.08 mmol, 1.1 equivalents). The resulting mixture was heated at 80 °C for 5 hours. The reaction was cooled and filtered through diatomaceous earth, washed with acetonitrile. The filtrate was concentrated under reduced pressure, and the crude material was purified by reversed-phase chromatography (acetonitrile in water) to provide the desired product (P.36) (90 mg, 52%).

[0764] 1H NMR (400MHz, methanol-d4) δppm:0.23(qd,1H),0.31-0.06(m,1H),0.55-0.39(m,2H),0.94-0.83(m,1H),2.02(d,3H),3.36 (dd,1H),3.56(dd,1H),3.97(s,3H),6.78(q,1H),7.29(t,1H),8.08(d,1H),8.18(s,1H),8.21(d,1H),8.42(d,2H).

[0765] LC-MS (Method 4): Retention time 1.17 min, m / z 505 [M+H] + ].

[0766] Example 6: 6,8-Dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4-amine (compound) Preparation of P.38)

[0767]

[0768] Step A: Preparation of N'-(2,4-dibromo-6-cyano-phenyl)-N,N-dimethylformamidin (intermediate I-13)

[0769]

[0770] 1,1-Dimethoxy-N,N-dimethyl-methylamine (0.228 mL, 1.63 mmol, 3 equivalents) was added to a solution of 2-amino-3,5-dibromobenzonitrile (CAS No. 68385-95-5, 150 mg, 0.54 mmol) in methanol (5 mL), and the reaction was stirred at 80 °C for 1 hour. The mixture was concentrated under reduced pressure to obtain a solid product (I-13) (179 mg, 99.5%), which was used directly in the next step.

[0771] LC-MS (Method 3): Retention time 1.17 min, m / z 505 [M+H] + ].

[0772] Step B: Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)acetone (intermediate I-14)

[0773]

[0774] Tributyl(pyrimidin-2-yl)stanane (CAS No. 153435-63-3, 25 g, 67.7 mmol, 1 equivalent), 1-(3-chloropyrazin-2-yl)acetone (CAS No. 2142-68-9, 12.37 g, 71.12 mmol, 1.05 equivalent), and toluene (500 mL) were added to a flask. The reaction mixture was purged with nitrogen for 10 min, and then copper iodide (I) (2.58 g, 13.55 mmol, 0.2 equivalent) and tetrakis(triphenylphosphine)palladium (O) (3.91 g, 3.39 mmol, 0.05 equivalent) were added. The reaction was then heated at 95 °C for 5 h. The mixture was cooled, filtered through diatomaceous earth, washed with ethyl acetate, and the filtrate was concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the product (I-14) as a brown solid (10 g, 51.6% yield).

[0775] LC-MS (Method 4): Retention time 0.37 min, m / z 201 [M+H + ].

[0776] Step C: Preparation of 1-(3-pyrimidin-2-ylpyrazin-2-yl)ethylamine (intermediate I-15)

[0777]

[0778] To a flask, 1-(3-pyrimidin-2-ylpyrazin-2-yl)acetone (I-14, 500 mg, 2.5 mmol, 1 equivalent), ammonium acetate (3.85 g, 50.0 mmol, 20 equivalents), and ethanol (25 mL) were added. Next, aqueous NH3 (28%) (7.5 mL) and sodium cyanoborohydride (0.50 g, 7.5 mmol, 3 equivalents) were added, and the mixture was heated at 80 °C for 2 hours. The mixture was cooled and concentrated under reduced pressure. The crude material was purified by reversed-phase column chromatography (C18 40–60 μm, acetonitrile in water) to give a brown, gelatinous product (I-15) (210 mg, 42%).

[0779] 1 H NMR (400MHz, DMSO-d6) δppm: 1.50 (d, J=6.6Hz, 3H), 4.93 (d, J=6.6Hz, 1H), 7.70 (t, J=5.0Hz, 1H), 8.86 (d, J=2.3Hz, 1H), 8.90 (d, J=2.4Hz, 1H), 9.07 (d, J=4.9Hz, 2H).

[0780] Step D: 6,8-Dibromo-N-[1-(3-pyrimidin-2-ylpyrazin-2-yl)ethyl]quinazolin-4-amine (compound) Preparation of P.38)

[0781]

[0782] In a vial, 1-(3-pyrimidin-2-ylpyrazin-2-yl)acetone (I-15, 120 mg, 0.59 mmol, 1.1 equivalent), N'-(2,4-dibromo-6-cyano-phenyl)-N,N-dimethylformamidinium (I-13, 179 mg, 0.54 mmol, 1 equivalent), and acetic acid (2.7 mL) were added. The mixture was stirred at 120 °C for 1 hour. Another batch of 1-(3-pyrimidin-2-ylpyrazin-2-yl)acetone (I-15, 135 mg) was added, and stirring was continued until the reaction was complete. The mixture was cooled, diluted with water, and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate, and concentrated under reduced pressure. Purification was performed by rapid silica gel chromatography (ethyl acetate in cyclohexane), followed by reversed-phase purification (acetonitrile in water), to provide the desired product (I-7) (83 mg, 32%) as a brown solid.

[0783] 1 H NMR (400MHz, DMSO-d6) δppm: 1.71 (d, J = 6.97Hz, 3H), 5.92 (quin, J = 6.79Hz, 1H), 7.53 (t, J = 4.77Hz, 1H), 8.15 (s, 1H), 8.28 (d, J = 1. 83Hz, 1H), 8.65 (d, J = 1.83Hz, 1H), 8.66 (d, J = 2.57Hz, 1H), 8.74 (d, J = 2.20Hz, 1H), 8.77 (d, J = 6.97Hz, 1H), 8.92 (d, J = 5.14Hz, 2H).

[0784] LC-MS (Method 3): Retention time 0.87 min, m / z 488 [M+H] + ].

[0785] Example 7: 6-[5-[1-[[2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4- [triazol-1-yl]pyridine-3-carboxynitrile (compound) P Preparation of .60)

[0786]

[0787] Step A: Preparation of 2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-amine (intermediate I-16)

[0788]

[0789] 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (I-7 prepared in Example 2, 300 mg, 1.18 mmol) and acetamide (0.7 g, 11.8 mmol, 10 equivalents) were charged into a sealed tube. The mixture was stirred at 180 °C for 4 days. The reaction was then cooled to room temperature and diluted with water (25 mL). The mixture was extracted three times with ethyl acetate (3 x 20 mL) and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-16) (102 mg, 29%) as a pale yellow solid.

[0790] 19 F NMR (377MHz, DMSO-d6) δppm: -60.36 (s, 1F), -59.63 (s, 1F).

[0791] LC-MS (Method 3): Retention time 0.95 min, m / z 296 [M+H] + ].

[0792] Step B: Preparation of 6-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyridine-3-carboxylonitrile (Intermediate I-18)

[0793]

[0794] To a solution of 2-bromopropionamide (CAS No. 5875-25-2, 4.00 g, 26.3 mmol, 1 equivalent) in dichloromethane, N,N-dimethylformamide dimethyl acetal (CAS No. 4637-24-5, 5.58 mL, 39.5 mmol, 1.5 equivalent) was added. The mixture was heated to reflux for 30 minutes. The reactants were then cooled to room temperature and concentrated under reduced pressure to provide a crude, yellow, oily product, 2-bromo-N-(dimethylaminomethylene)propionamide (I-17) (5.6 g, 98%), which was used as is in the next step.

[0795] 1 H NMR (400MHz, CDCl3) δppm: 1.85 (d, J = 6.97Hz, 3H), 3.14 (d, J = 0.73Hz, 3H), 3.17 (s, 3H), 4.55 (q, J = 6.85Hz, 1H), 8.49 (s, 1H).

[0796] 5-Cyano-2-hydrazinopyridine (CAS No. 104408-24-4, 4.68 g, 25.2 mmol, 1.05 equivalent) was added to a solution of 2-bromo-N-(dimethylaminomethylene)acrylamide (I-17, 5.40 g, 24 mmol, 1 equivalent) in 1,4-dioxane (54 mL). Acetic acid (54 mL) was then slowly added. The resulting red solution was heated to 80 °C for 1 hour. The reaction mixture was cooled and concentrated under reduced pressure. The mixture was then absorbed into ethyl acetate and washed with a saturated aqueous solution of sodium bicarbonate and water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (I-18) (3.1 g, 46%) as a white solid.

[0797] 1 H NMR (400MHz, CDCl3) δppm: 2.26 (d, J = 6.97Hz, 3H), 6.43 (q, J = 6.97Hz, 1H), 8.05 (s, 1H), 8.14-8.20 (m, 2H), 8.85 (dd, J = 1.83, 1.10Hz, 1H).

[0798] LC-MS (Method 3): Retention time 0.88 min, m / z 278-280 (Br mode) [M+H] + ].

[0799] Step C: 6-[5-[1-[[2-methyl-6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4- [triazol-1-yl]pyridine-3-carboxynitrile (compound) P Preparation of .60)

[0800]

[0801] 2-Methyl-6,8-bis(trifluoromethyl)quinazolin-4-amine (I-16, 106 mg, 0.36 mmol), acetonitrile (1.43 mL), cesium carbonate (351 mg, 1.08 mmol, 3 equivalents), and 6-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyridin-3-carboxylonitrile (I-18, 110 mg, 0.40 mmol, 1.1 equivalents) were charged into a sealed tube, and the reaction mixture was heated to 50 °C for 3 h. The reaction mixture was cooled, diluted with water (60 mL), and extracted three times with ethyl acetate (3 x 60 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (134 mg, 76% yield) as a yellow solid.

[0802] 1H NMR (400MHz, DMSO-d6) δppm: 1.49-1.58(m,3H),4.09-4.19(m,1H),6.49-6.55(m,1H),7.13-7.22(m, 1H),7.63-7.71(m,1H),7.83-7.90(m,1H),8.17-8.24(m,1H),8.60-8.66(m,1H),9.23-9.29(m,1H).

[0803] LC-MS (Method 3): Retention time 1.16 min, m / z 494 [M+H] + ].

[0804] Example 8: 6,8-Dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]quinoline-4-amine (compound) Preparation of substance P.67

[0805]

[0806] Sodium hydride (20.7 mg, 0.516 mmol, 1.10 equivalents) was added dropwise to a solution of 6,8-dichloroquinoline-4-amine (100 mg, 0.469 mmol) in N,N-dimethylformamide (0.94 mL) at room temperature. The reaction mixture was stirred at this temperature for 10 minutes. Then, a solution of 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (125 mg, 0.493 mmol, 1.05 equivalents) in N,N-dimethylformamide (0.94 mL) was added dropwise to the reaction mixture and stirred at room temperature for 1 hour. The mixture was poured into water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane, then methanol in dichloromethane) to provide the desired product (39 mg, 0.10 mmol) as a pale orange solid.

[0807] 1 ¹H NMR (400MHz, chloroform-d) δppm: 1.75-1.84 (m, 3H) 6.08-6.20 (m, 1H) 6.28-6.37 (m, 1H) 6.51-6.58 (m, 1H) 7.45-7.51 (m, 1H) 7.75-7.86 (m, 2H) 8.17-8.12 (m, 1H) 8.60-8.66 (m, 1H) 8.94-9.02 (m, 2H).

[0808] LC-MS (Method 1): Retention time 0.63 min, m / z 386-390 [M+H] + (Dichloromode).

[0809] Example 9: 6,8-Dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]quinazolin-4-amine (chemical) Preparation of compound P.68

[0810]

[0811] Step A: Preparation of 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (intermediate I-20)

[0812]

[0813] At room temperature, 1,1-dimethoxy-N,N-dimethyl-methylamine (CAS 4637-24-5, 2.49 mL, 18.8 mmol, 2.00 equivalents) was added to a solution of 2-bromopropionamide (CAS 5875-25-2, 1.50 g, 9.38 mmol) in dichloromethane (37.5 mL). The reaction mixture was heated to 40 °C and stirred for 2.5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to provide a quantitative crude intermediate (I-19).

[0814] LC-MS (Method 1): Retention time 0.26 min, m / z 207-209 [M+H] + (Br mode).

[0815] A mixture of intermediate I-1 (1.94 g, 9.38 mmol), acetic acid (28.1 mL), and pyrimidin-2-ylhydrazine (1.24 g, 11.3 mmol, 1.20 equivalents) was heated to 65 °C and stirred for 2 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-20) (1.70 g, 6.69 mmol) as a pale yellow solid.

[0816] 1 ¹H NMR (400MHz, chloroform-d) δppm: 2.20-2.31 (m, 3H) 6.34-6.48 (m, 1H) 7.37-7.45 (m, 1H) 8.05-8.15 (m, 1H) 8.88-8.95 (m, 2H).

[0817] LC-MS (Method 1): Retention time 0.66 min, m / z 254-256 [M+H] + (Br mode).

[0818] Step B: 6,8-Dichloro-N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]quinazolin-4-amine (chemical) Preparation of compound P.68

[0819]

[0820] At room temperature, cesium carbonate (1.83 g, 5.61 mmol, 3.00 equivalents) and 2-[5-(1-bromoethyl)-1,2,4-triazol-1-yl]pyrimidine (intermediate I-20 prepared as described above, 522 mg, 2.06 mmol, 1.10 equivalents) were added to a solution of 6,8-dichloroquinazoline-4-amine (400 mg, 1.87 mmol) in acetonitrile (7.47 mL). The reaction mixture was heated to 50 °C and stirred overnight. After cooling to room temperature, the reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude material by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (351 mg, 0.907 mmol) as a yellow solid.

[0821] LC-MS (Method 1): Retention time 0.81 min, m / z 387-391 [M+H] + (Dichloromode).

[0822] Example 10: N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5,7-bis(trifluoromethyl)isoquine Preparation of 1-Lin-amine (compound P.83)

[0823]

[0824] Step A: Preparation of 2-iodo-3,5-bis(trifluoromethyl)benzonitrile (intermediate I-21)

[0825]

[0826] 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (I-7, prepared as in Example 2, 2.19 g, 8.62 mmol, 1 equivalent) was dissolved in diiodomethane (6.9 mL) and acetonitrile (13.8 mL). Isoamyl nitrite (2.3 mL, 16.4 mmol, 1.9 equivalent) was then added under an argon atmosphere. The reaction mixture was stirred at 50 °C for 60 min, then at 80 °C for 60 min. The reaction mixture was concentrated under reduced pressure and diluted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give a crude mixture of oil and solids. The oil was purified by rapid silica gel chromatography (ethyl acetate in cyclohexane), and the resulting solid was combined with the crude solids material to provide the desired product (I-21) (2.2 g, 70%).

[0827] 1 H NMR (400MHz, CDCl3) δppm: 7.99-8.02 (m, 1H), 8.03-8.07 (m, 1H).

[0828] Step B: Preparation of 3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde (intermediate I-23) Preparation

[0829]

[0830] 2-Iodo-3,5-bis(trifluoromethyl)benzonitrile (I-21 prepared above, 3.52 g, 9.64 mmol, 1 equivalent) was dissolved in toluene (72 mL), and the solution was cooled to -78 °C and stirred for 90 min. The reaction was warmed to room temperature and quenched by slow addition of aqueous hydrochloric acid (1 M, 50 mL). The mixture was extracted with ethyl acetate (50 mL), and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to provide crude 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (I-22), which was used as is in the next step.

[0831] Under an Ar atmosphere, 2-iodo-3,5-bis(trifluoromethyl)benzaldehyde (I-22 prepared above, 3.5 g, 9.51 mmol, 1 equivalent) was dissolved in triethylamine (47.5 mL). Next, cuprous iodide (I) (0.073 g, 0.38 mmol, 0.04 equivalent), bis(triphenylphosphine)palladium dichloride (II) (0.135 g, 0.19 mmol, 0.02 equivalent), and trimethylsilylacetylene (3.39 mL, 23.8 mmol, 2.5 mmol) were added sequentially, and the mixture was stirred at 80 °C. After 17 hours, the reaction was cooled, concentrated under reduced pressure, and the material was dissolved in ethyl acetate. The organic layer was washed twice with dilute hydrochloric acid aqueous solution (2 x 20 mL) and brine, then filtered and concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (I-23) (1.076 g, 33%).

[0832] 1 H NMR (400MHz, CDCl3) δppm: 6.33 (br s, 1H), 7.97 (br s, 1H), 8.33 (s, 1H), 8.66 (br s, 1H), 11.57 (br s, 1H).

[0833] LC-MS (Method 3): Retention time 1.34 min, m / z 339 [M+H] + ].

[0834] Step C: Preparation of 5,7-bis(trifluoromethyl)isoquinoline (intermediate I-24)

[0835]

[0836] Weigh 3,5-bis(trifluoromethyl)-2-(2-trimethylsilylethynyl)benzaldehyde (I-23 prepared above, 1.075 g, 3.18 mmol, 1 equivalent) into a microwave tube and add ammonia solution (7 M in methanol, 10 mL). The tube is then sealed and heated in a microwave reactor at 130 °C for 15 minutes. The solvent is then removed under reduced pressure to provide the desired product (I-24) (820 mg, 97%).

[0837] 1 H NMR (400MHz, CDCl3) δppm: 7.99-8.10 (m, 1H), 8.26 (s, 1H), 8.53 (s, 1H), 8.85 (d, J = 6.24Hz, 1H), 9.50 (s, 1H).

[0838] LC-MS (Method 3): Retention time 1.05 min, m / z 266 [M+H] + ].

[0839] Step D: Preparation of 2-oxide-5,7-bis(trifluoromethyl)isoquinoline-2-onium (intermediate I-25)

[0840]

[0841] 5,7-Bis(trifluoromethyl)isoquinoline (I-24 prepared above, 875 mg, 3.3 mmol, 1 equivalent) was absorbed into acetic acid (5.5 mL) and H₂O₂ (35 wt%) (0.85 mL, 9.9 mmol, 3 equivalent) was added. The mixture was then heated to 70 °C. After 17 hours, the reaction was cooled and diluted with ethyl acetate, and water and NaOH (4 M) were added until pH 12 was reached. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide the desired product (I-25) (1.040 g, quantified).

[0842] 1 H NMR (400MHz, CDCl3) δppm: 1 ¹H NMR (400MHz, solvent) δppm 8.05 (br d, J = 7.34Hz, 1H), 8.08 (s, 1H), 8.20 (s, 1H), 8.36 (dd, J = 7.52, 1.65Hz, 1H), 8.90 (s, 1H).

[0843] LC-MS (Method 3): Retention time 0.85 min, m / z 282 [M+H] + ].

[0844] Step E: N-[1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5,7-bis(trifluoromethyl)isoquinoline- Preparation of 1-amine (compound P.83)

[0845]

[0846] Add N,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5 equivalents) and bromotripyrrolidinephosphonium hexafluorophosphate to a flask containing 2-oxy-5,7-bis(trifluoromethyl)isoquinoline-2-onium (I-25, 50 mg, 0.18 mmol.1 equivalents prepared above) dissolved in dichloromethane (0.89 mL) and 1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylamine hydrochloride (similar to the preparation on page 128 of WO2019 / 197468, 80.6 mg, 0.356 mmol, 2 equivalents). 211 mg, 0.44 mmol, 2.5 equivalents) and the reaction was stirred at room temperature. After 4 hours, more N,N-diisopropylethylamine (0.155 mL, 0.89 mmol, 5 equivalents) and tripyrrolidinyl phosphonium hexafluorophosphate (PH6) were added. 211 mg, 0.44 mmol, 2.5 equivalents). After 17 hours, the reaction was filtered and the crude product was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product P.38 (30 mg, 37%).

[0847] 1 H NMR (400MHz, CDCl3) δppm: 1.84 (d, J = 6.60Hz, 3H), 6.15-6.97 (m, 1H), 6.56 (quin, J = 7.06Hz, 1H), 7.04 (dd ,J=5.69,2.02Hz,1H),7.44(t,J=4.77Hz,1H),7.63(brd,J=7.34Hz,1H),7.92(d,J=6.24Hz,1H),7.94(br s,1H),8.10(s,1H),8.41(s,1H),8.98(d,J=4.77Hz,2H).

[0848] 19 F NMR (377MHz, CDCl3) δppm: -62.15 (s, 1F), -61.08 (s, 1F).

[0849] LC-MS (Method 3): Retention time 1.08 min, m / z 454 [M+H] + ].

[0850] Example 11: 6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)cenolin-4-yl]amino]ethyl]-1,2,4-tri Preparation of [azol-1-yl]pyridine-3-carboxynitrile (compound P.135)

[0851] Step A: Preparation of 6,8-bis(trifluoromethyl)cinolin-4-ol (I-26)

[0852]

[0853] 1-[2-amino-3,5-bis(trifluoromethyl)phenyl]ethyl ketone (CAS No.: 1805121-99-6, 1.25 g, 4.61 mmol, 1 equivalent) was dissolved in glacial acetic acid (18.4 mL) and 70% sulfuric acid (0.92 mL, 12.1 mmol, 2.63 equivalents). The solution was cooled to 22 °C, and sodium nitrite (389 mg, 5.53 mmol, 1.2 equivalents) in an ice-cold solution of water (3.55 mL) was added dropwise while cooling. After 45 min, triethylamine (1.81 mL, 12.91 mmol, 2.8 equivalents) was added, and the reaction was stirred at room temperature for 17 h. The mixture was poured into 100 mL of ice water and extracted with ethyl acetate (2 x 60 mL). The combined organic layers were washed with saturated Na₂CO₃ solution and brine, dried over anhydrous MgSO₄, and concentrated under reduced pressure. The desired product (I-26) (907 mg, 63%) was obtained by purification using silica gel rapid chromatography (ethyl acetate in cyclohexane).

[0854] 1 H NMR (400MHz, CDCl3) δppm: 10.32 (br s, 1H) 8.79 (s, 1H) 8.21 (s, 1H) 7.99 (s, 1H).

[0855] 19 F NMR (377MHz, CDCl3) δppm: -60.61 (s, 3F) - 62.65 (s, 3F).

[0856] LC-MS (Method 3) retention time 0.88 min m / z 283 [M+H + ].

[0857] Step B: Preparation of 4-chloro-6,8-bis(trifluoromethyl)zoline (I-27)

[0858]

[0859] 6,8-bis(trifluoromethyl)cinolin-4-ol (I-26, 840 mg, 2.98 mmol, 1 equivalent) was suspended in toluene (5.95 mL), and phosphorus trichloride (0.31 mL, 3.28 mmol, 1.1 equivalent) was added. The mixture was heated to 50 °C for 17 h. The reaction was quenched with saturated ammonium chloride solution and diluted with ethyl acetate. The pH was adjusted to 10-12 with ammonia. The organic layer was washed five times with brine. It was washed with anhydrous MgSO4 and concentrated under reduced pressure to give (I-27) (1.04 g, 93% yield, 80% purity).

[0860] 1H NMR (400MHz, CDCl3) δppm: 9.67 (s, 1H) 8.78 (s, 1H) 8.43 (s, 1H).

[0861] 19 F NMR (377MHz, CDCl3) δppm: -59.6 (s, 3F) - 63.4 (s, 3F).

[0862] LC-MS (Method 3) Retention time 1.11 min m / z 301 [M+H + ].

[0863] Step C: Preparation of (2S)-2-[[6,8-bis(trifluoromethyl)cenolin-4-yl]amino]acrylamide (I-28)

[0864]

[0865] 4-Chloro-6,8-bis(trifluoromethyl)cenline (I-27, 1.04 g, 3.46 mmol, 1 equivalent), potassium carbonate (2.39 g, 17.3 mmol, 5 equivalents), and (2S)-2-aminopropionamide hydrochloride (2.22 g, 17.3 mmol, 5 equivalents) were heated to 50 °C for 60 h in NMP (13.8 mL). The reaction mixture was diluted with water (100 mL) and ethyl acetate (100 mL). The organic layer was washed with water (30 mL) and brine (30 mL), dried over anhydrous Na₂SO₄, and concentrated under reduced pressure to give (I-28) (1.57 g, 73%).

[0866] 1 H NMR (400MHz, DMSO-d6) δppm: 9.35 (s, 1H) 8.78 (s, 1H) 8.38-8.19 (m, 2H) 7.76 (s, 1H) 7.29 (s, 1H) 4.41 (quin, J = 7.0Hz, 1H) 1.56 (d, J = 7.0Hz, 3H)

[0867] 19 F NMR(377MHz,DMSO-d6)δppm:-58.9(s,3F)-60.9(s,3F)

[0868] LC-MS (Method 3): Retention time 0.86 min, m / z 353 [M+H] + ].

[0869] Step D: (NE,2S)-2-[[6,8-bis(trifluoromethyl)cenline-4-yl]amino]-N-(dimethylaminomethylene) Preparation of (I-29) Acrylamide

[0870]

[0871] (2S)-2-[[6,8-bis(trifluoromethyl)cenolin-4-yl]amino]acrylamide (I-28, 500 mg, 1.42 mmol, 1 equivalent) was mixed with 2-methyltetrahydrofuran (14.2 ml) and DMF-DMA (377 μl, 2.84 mmol, 2 equivalents) and heated to 50 °C for 30 min. The reaction mixture was evaporated under reduced pressure to give (I-29) (642 mg, 99%).

[0872] LC-MS (Method 3): Retention time 0.92 min, m / z 408 [M+H] + ].

[0873] Step E: 6-[5-[(1R)-1-[[6,8-bis(trifluoromethyl)cenolin-4-yl]amino]ethyl]-1,2,4-triazole- Preparation of 1-yl]pyridine-3-carboxynitrile (compound P.135)

[0874]

[0875] (NE,2S)-2-[[6,8-bis(trifluoromethyl)benzolin-4-yl]amino]-N-(dimethylaminomethylene)acrylamide (I 29, 306 mg, 0.75 mmol, 1 equivalent) was dissolved in 2-methyltetrahydrofuran (3 mL). 6-hydrazinonitrile (191 mg, 1.35 mmol, 1.8 equivalent) and acetic acid (1.88 mL) were added. The mixture was heated to 70 °C for 1 h. It was cooled to 25 °C and diluted with ethyl acetate (30 mL). It was washed with water, saturated Na₂CO₃ solution, and brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The desired product (P.135) (87 mg, 24%) was obtained by rapid silica gel chromatography (ethyl acetate in cyclohexane) followed by reverse-phase purification (acetonitrile in water).

[0876] 1 H NMR (400MHz, CDCl3) δppm: 9.03-8.99 (m, 2H) 8.94 (br s, 1H) 8.30 (s, 1H), 8.27-8.23 (m, 2H) 8.06 (s, 1H) 6.44 (q, J = 6.6Hz, 1H) 1.95 (d, J = 6.6Hz, 3H).

[0877] 19 F NMR (377MHz, CDCl3) δppm: -60.14 (s, 3F) - 62.78 (s, 3F).

[0878] LC-MS (Method 3): Retention time 1.01 min, m / z 480 [M+H] + ].

[0879] Example 12: 4-[[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]amino]-6, Preparation of 8-bis(trifluoromethyl)quinoline-3-carboxynitrile (compound P.139)

[0880]

[0881] Step A: Ethyl(Z)-3-[2,4-bis(trifluoromethyl)aniline]-2-cyano-prop-2-enoate (compound I- Preparation of 30)

[0882]

[0883] A mixture of ethyl (ethoxymethylene) cyanoacetate (1.46 g, 8.47 mmol, 2 equivalents) and 2,4-bis(trifluoromethyl)aniline (1 g, 4.23 mmol, 1 equivalent) was heated to 140 °C for 1 h. The mixture was cooled to 25 °C and washed with a mixture of TBME:cyclohexane 30:70. The solids were filtered off and dried to give (I-30) (490 mg, 33%).

[0884] 1 H NMR (400MHz, DMSO-d6) δppm: 11.34 (br d, J = 12.5Hz, 1H) 8.82 (d, J = 12.4Hz, 1H) 810-8.18 (m, 2H) 8.05 (s, 1H) 4.28 (q, J = 7.2Hz, 2H) 1.28 (t, J = 7.1Hz, 3H).

[0885] LC-MS (Method 4): Retention time 1.19 min, m / z 353 [M+H] + ].

[0886] Step B: Preparation of 4-oxo-6,8-bis(trifluoromethyl)-1H-quinoline-3-carboxynitrile (compound I-31)

[0887]

[0888] Ethyl (Z)-3-[2,4-bis(trifluoromethyl)aniline]-2-cyano-prop-2-enoate (I-30, 500 mg, 1.42 mmol, 1 equivalent) was heated to 260 °C for 8 h in a phenyl ether-biphenyl eutectic mixture (2.5 mL). After cooling to room temperature, it was diluted with cyclohexane to precipitate the product. It was washed with methyl tert-butyl ether and dried under reduced pressure to give (I-31) (180 mg, 41%).

[0889] 1 H NMR (400MHz, DMSO-d6) δppm: 8.68 (s, 1H) 8.66 (s, 1H) 8.45 (s, 1H).

[0890] LC-MS (Method 4): Retention time 0.95 min, m / z 307 [M+H] + ].

[0891] Step C: Preparation of 4-chloro-6,8-bis(trifluoromethyl)quinoline-3-carboxynitrile (compound I-32)

[0892]

[0893] 4-O-6,8-bis(trifluoromethyl)-1H-quinoline-3-carboxynitrile (I-31, 600 mg, 1.96 mmol, 1 equivalent) and thionyl chloride (6 mL, 80.6 mmol, 41 equivalent) were mixed together with N,N-dimethylformamide (30 μl, 0.39 mmol, 0.2 equivalent). The mixture was heated to 80 °C for 3 h. It was concentrated under reduced pressure and purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to give (I-32) (423 mg, 66%).

[0894] 1 H NMR (400MHz, CDCl3) δppm: 9.24 (s, 1H) 8.86 (s, 1H) 8.47 (s, 1H).

[0895] LC-MS (Method 4): Retention time 1.16 min, m / z 325 [M+H] + ].

[0896] Step D: tert-butylN-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl] Preparation of carbamate (compound I-33)

[0897]

[0898] Tert-butyl N-[(1S)-2-amino-1-methyl-2-oxo-ethyl]carbamate (70 g, 353 mmol, 1 equivalent) was mixed with 2-methyltetrahydrofuran (1.12 l) and DMF-DMA (70 ml, 530 mmol, 1.5 equivalent) and heated to 40 °C for 2 h. The reaction mixture was concentrated under reduced pressure to give (I-33) (105 g, 97% yield, 80% purity).

[0899] 1 H NMR (400MHz, CDCl3) δppm: 8.38 (s, 1H) 5.98-6.15 (m, 1H) 4.25-4.37 (m, 1H) 3.16 (s, 3H) 3.09 (s, 3H) 1.46 (s, 9H) 1.40 (m, 3H).

[0900] step E N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate Preparation of (Compound I-34)

[0901]

[0902] Tert-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (I-33, 80% purity, 50 g, 164 mmol, 1 equivalent) was dissolved in 1,4-dioxane (510 mL). 6-hydrazinopyridine-3-carboxynitrile (33.1 g, 247 mmol, 1.5 equivalent) and glacial acetic acid (510 mL) were added to the mixture. The mixture was heated to 90 °C for 30 min. After cooling to 25 °C, the reaction mixture was concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) gave (I-34) (23 g, 32%).

[0903] 1 H NMR (400MHz, CDCl3) δppm: 8.80 (dd, J = 1.90, 0.8Hz, 1H) 8.10-8.20 (m, 1H) 7.98 (s, 1H) 5.92-6.02 (m, 1H) 5.77 (br d,J=8.6Hz,1H)4.12(q,J=7.1Hz,2H)1.58(d,J=6.8Hz,3H)1.42(s,6H).

[0904] Step F: [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]ammonium; 2,2,2-trifluoro Preparation of acetate (compound I-35)

[0905]

[0906] Tert-butyl N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate (I-34, 1.1 g, 3.5 mmol, 1 equivalent) was dissolved in methanol (11 mL) and trifluoroacetic acid (5.6 mL, 70 mmol, 20 equivalent) was added. The mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated under reduced pressure.

[0907] Add MTBE to the crude oily substance and stir for 5 min. Decant the MTBE and add MTBE a second time. Precipitate the product, filter it and dry it to give (I-35) (600 mg, 50%).

[0908] LC-MS (Method 5): Retention time 0.31 min, m / z 215 [M+H] + ].

[0909] Step G: 4-[[(1S)-1-[2-(5-cyano-2-] - (pyridyl)-1,2,4-triazol-3-yl]ethyl]amino]-6,8- Preparation of bis(trifluoromethyl)quinoline-3-carboxynitrile (compound P.139)

[0910]

[0911] In a round-bottom flask, [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]ammonium; 2,2,2-trifluoroacetate (I-34, 546 mg, 1.66 mmol, 1.2 equivalents), 4-chloro-6,8-bis(trifluoromethyl)quinoline-3-carboxynitrile (I-32, 450 mg, 1.3863 mmol, 1 equivalent) and potassium carbonate (581 mg, 4.16 mmol, 3 equivalents) were suspended in acetonitrile (9 mL). The reactants were heated to 60 °C for 2 h. The reaction was quenched with water and stirred for 20 min. P.139 precipitate was obtained as a solid, filtered (432 mg, 62%), washed with water, and dried under reduced pressure.

[0912] 1 H NMR(400MHz,DMSO-d6)δppm 9.30(s,1H)8.95(d,J=7.8Hz,1H)8.89-8.93(m,1H)8.73(s,1H)8.49(dd,J=8.6,2.1Hz,1H )8.35(s,1H)8.31(s,1H)8.07(d,J=8.7Hz,1H)6.58(t,J=7.1Hz,1H)1.91(d,J=6.6Hz,3H).

[0913] 19 F NMR (377MHz, DMSO-d6) δppm-59.16 (s, 3F), -60.26 (s, 3F).

[0914] LCMS (Method 4): Retention time: 1.18 min, m / z 503 [M+H] + ].

[0915] Example 13: 6-Chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)-1-[2-[5-[4-(trifluoromethyl)] ) Thiazole-2- Preparation of [2-pyridyl]-1,2,4-triazol-3-yl]ethyl]quinazolin-4-amine (compound P.142)

[0916]

[0917] Step A: 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-tri Preparation of [1-azolyl]pyridine-3-carboxynitrile (I-36)

[0918]

[0919] The following were added to a flask: 4,6-dichloro-8-(trifluoromethyl)quinazoline (CAS No.: 1565368-05-9, 100 mg, 0.37 mmol, 1 equivalent), [(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]ammonium; 2,2,2-trifluoroacetate (I-35 from Example 12, 74% purity, 199 mg, 0.45 mmol, 1.2 equivalent), cesium carbonate (366 mg, 1.12 mmol, 3 equivalent), and acetonitrile (1 mL). The reaction was stirred at 25 °C for 16 h. The mixture was diluted with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-36). (107 mg, 64%).

[0920] 1 H NMR (400MHz, DMSO-d6) δppm: 9.11 (d, J = 6.9Hz, 1H) 9.04 (d, J = 1.5Hz, 1H) 8.98-9.00 (m, 1H) 8.93 (d, J = 2.2Hz, 1H) 8.5 7(dd,J=8.6,2.2Hz,1H)8.34(s,1H)8.18-8.23(m,2H)8.06-8.10(m,1H)6.37(t,J=6.85Hz,1H)1.74(,J=7.0Hz,3H).

[0921] LCMS (Method 4): Retention time: 1.07 min, m / z 445 [M+H] + ].

[0922] Step B: 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1, Preparation of 2,4-triazol-1-yl]pyridine-3-carboxylonitrile (I-37)

[0923]

[0924] 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridin-3-carboxylonitrile (I-36, 1.40 g, 3.15 mmol, 1 equivalent) was weighed together with acetonitrile (15.7 mL), cesium carbonate (3.08 g, 9.44 mmol, 3 equivalents), and iodomethane (396 μl, 6.29 mmol, 2 equivalents) in a sealable tube. The tube was sealed and heated to 50 °C for 16 h. After cooling to 25 °C, it was extracted twice with ethyl acetate. It was washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. It was purified by silica gel rapid chromatography (ethyl acetate in dichloromethane 3:1) to give (I-37).

[0925] 1 H NMR(600MHz,DMSO-d6)δppm 8.50(dd,J=8.5,2.20Hz,1H)8.45(s,2H)8.32(s,1H)8.32(s,1H)8.22(d,J=1.9Hz,1H)8.09( d,J=2.1Hz,1H)8.05(d,J=8.5Hz,1H)6.67(q,J=6.9Hz,1H)3.26(s,3H)1.83(d,J=6.9Hz,3H).

[0926] LCMS (Method 3): Retention time: 1.08 min, m / z 459 [M+H] + ].

[0927] Step C: 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl].methyl-amino]ethyl]-1, Preparation of 2,4-triazol-1-yl]pyridine-2-thiocarboxamide (I-38)

[0928]

[0929] An aqueous solution of ammonium sulfide (2.23 mL, 6.54 mmol, 5 equivalents) was added to a solution of 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridin-3-carboxynitrile (I-37, 600 mg, 1.31 mmol, 1 equivalent) in pyridine (4.8 mL). The solution was stirred at 25 °C for 16 h. The solution was diluted with water and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. The solution was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to give (I-38) (468 mg, 73%).

[0930] 1 H NMR(400MHz,DMSO-d6)δppm 10.06(br s,1H)9.66(br s,1H)8.44(s,1H)8.40(s,1H)8.41(d,J=7.4Hz,2H)8.27(s,1H)8.17(d,J=2.0Hz,1H)8.05(d ,J=2.1Hz,1H)7.89(d,J=8.0Hz,1H)6.68(d,J=7.0Hz,1H)3.26(s,3H)1.83(d,J=7.0Hz,3H).

[0931] 19 F NMR (377MHz, DMSO-d6) δppm-59.39 (s, 3F).

[0932] LCMS (Method 4): Retention time: 1.10 min, m / z 493 [M+H] + ].

[0933] Step D: 2-[6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl Preparation of [I-39]-1,2,4-triazol-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazolyl-4-ol (I-39)

[0934]

[0935] 6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl].methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridine-2-thiocarboxamide (I-38, 100 mg, 0.20 mmol, 1 equivalent) was dissolved in N,N-dimethylformamide (2.5 mL). 3-bromo-1,1,1-trifluoroacetone (32.2 μl, 0.30 mmol, 1.5 equivalent) was added to the solution, and the mixture was heated to 60 °C for 2 h. The solution was cooled to 25 °C and diluted with ethyl acetate. It was washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure.

[0936] It was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to give (I-39) (103 mg, 76%, 90% purity).

[0937] 1 H NMR (400MHz, acetonitrile-d3) δppm: 8.52 (d, J = 4.4Hz, 1H) 8.32 (ddd J=12.2,8.6,2.3Hz)8.07-8.15(m,1H)8.06-8.12(m,1H),8.03(s,1H)7.95(dd,J=8. 6,5.1Hz,1H)7.8(d,J=2.3Hz,1H)7.73(d,J=2.2Hz,1H)6.76(t,J=7.6Hz,1H)5.05(br dd,J=16.7,2.6Hz,1H)3.78(dd,J=13.0Hz,10.8Hz,1H)3.61(s,1H)3.47-3.5 5(m,1H)3.12(d,J=7.5Hz,3H)2.09-2.21(m,5H)1.87(dd,J=6.9,1.3Hz,3H).

[0938] LCMS (Method 4): Retention time: 1.17 min, m / z 604 [M+H] + ].

[0939] Step E: 6-Chloro-N-methyl-8-(trifluoromethyl)-N-[(1S)-1-[2-[5-[4-(trifluoromethyl)thiazole-2- Preparation of [2-pyridyl]-1,2,4-triazol-3-yl]ethyl]quinazolin-4-amine (compound P.142)

[0940]

[0941] Triethylamine (58.4 μl, 0.41 mmol, 2.5 equivalents) was added to a solution of 2-[6-[5-[(1S)-1-[[6-chloro-8-(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]-3-pyridyl]-4-(trifluoromethyl)-5H-thiazolyl-4-ol (I-39, 100 mg, 0.17 mmol, 1 equivalent) in tetrahydrofuran (4 mL) and cooled to 0 °C. Trifluoroacetic anhydride (118 μl, 0.83 mmol, 5 equivalents) was added at 0 °C. The reaction mixture was heated to room temperature and stirred for 16 h. It was quenched with saturated NaHCO3 solution and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give a gel. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product P.142 (47 mg, 48% yield).

[0942] 1 H NMR(400MHz, DMSO-d6)δppm 8.65(s,1H)8.55(s,1H)8.50(dd,J=8.5,2.3Hz,1H)8.31(s,1H)8.27-8.30(m,1H)8.06(s,1H)7.97(d,J=8.3Hz 1H)7.85(s,1H)6.65(br d,J=6.8Hz,1H)3.10(s,3H)1.88(d,J=6.8Hz,3H).

[0943] 19 F NMR (377MHz, DMSO-d6) δppm-59.6(s,3F)-62.5(s,3F).

[0944] LCMS (Method 4): Retention time: 1.26 min, m / z 585 [M+H] + ].

[0945] Example 14: N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis ( (trifluoromethyl)- Preparation of 1,2,3-benzotriazine-4-amine (compound P.145)

[0946]

[0947] Step A: Preparation of 2-amino-3,5-bis(trifluoromethyl)benzamide (I-40)

[0948]

[0949] 2-Amino-3,5-bis(trifluoromethyl)benzonitrile (CAS No. 473740-86-2, 1.00 g, 3.94 mmol, 1 equivalent) and potassium carbonate (109 mg, 0.79 mmol, 0.2 equivalent) were dissolved in methanol (15 ml) and water (2 ml). While stirring at 25 °C, urea peroxide (1.14 g, 11.81 mmol, 3 equivalent) was added, and the mixture was stirred for 1 h.

[0950] Next, a second batch of urea peroxide (1.14 g, 11.81 mmol, 3 equivalents) was added and stirred for 16 h. Sodium metabisulfite (1 g) was added and stirred for 5 min. It was then diluted with ethyl acetate. The solid was filtered off and the filtrate was concentrated under reduced pressure. The crude material was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-40) (818 mg, 76%).

[0951] 1 H NMR (400MHz, DMSO-d6) δppm 8.22-8.39 (br s, 1H) 8.18 (s, 1H) 7.78 (s, 1H) 7.50-7.70 (br s, 3H).

[0952] LCMS (Method 3): Retention time: 0.91 min, m / z 273 [M+H] + ].

[0953] Step B: Preparation of 6,8-bis(trifluoromethyl)-3H-1,2,3-benzotriazine-4-one (I-41)

[0954]

[0955] A solution of 2-amino-3,5-bis(trifluoromethyl)benzamide (I-40, 816 mg, 3 mmol, 1 equivalent) in 1N hydrogen chloride (12 ml) was stirred for 20 min at 0 °C. A solution of sodium nitrite (414 mg, 6 mmol, 2 equivalent) in water (10 ml) was added dropwise over 40 min. The mixture was then stirred at 0 °C for 2 h. 4M sodium hydroxide was added to adjust the pH to 8, and the mixture was stirred vigorously for 15 min. The solid was filtered off, and the filtrate was acidified to pH 2-3 with HCl. The solid product was filtered off and dried to give (I-41) (382 mg, 45%).

[0956] 1 H NMR (400MHz, DMSO-d6) δppm 15.56-15.89 (br s, 1H) 8.77 (s, 1H) 8.71 (s, 1H).

[0957] LCMS (Method 3): Retention time: 0.92 min, m / z 284 [M+H]+ ].

[0958] Step C: tert-butyl N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]carbamate (I- Preparation of 42)

[0959]

[0960] Tert-butyl N-[(1S)-2-[(E)-dimethylaminomethyleneamino]-1-methyl-2-oxo-ethyl]carbamate (I-33 from Example 12, 4.23 g, 17.4 mmol, 1 equivalent) pyrimidine 2-hydrazine (2.87 g, 26.1 mmol, 1.5 equivalent) was mixed with 1,4-dioxane (43.5 ml) and glacial acetic acid (43.5 ml). The mixture was heated to 90 °C for 35 min. It was concentrated under reduced pressure and purified by rapid column chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-42) (4.03 g, 80%).

[0961] 1 H NMR (400MHz, CDCl3) δppm 8.89(d,J=4.8Hz,2H)8.03(s,1H)7.37(t,J=5.0Hz,1H)5.91-6.11(m,1H)5.55-5-77(m,1H)1.58(d,J=6.6Hz,3H)1.35-1.47(m,9H).

[0962] LCMS (Method 3): Retention time: 0.73 min, m / z 291 [M+H] + ].

[0963] Step D: [(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]ammonium; 2,2,2-trifluoroacetate Preparation of (I-43)

[0964]

[0965] Tert-butyl N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]carbamate (I-42, 36.0 g, 86.6 mmol, 1 equivalent) was dissolved in dichloromethane (540 mL) and trifluoroacetic acid (180 mL, 2.27 mol, 26.2 equivalents) was added. The mixture was stirred at 25 °C for 2 h. The reaction mixture was concentrated under reduced pressure.

[0966] Add methyl tert-butyl ether (72 ml) to the crude oily product and stir for 5 min. Decant MTBE and add acetonitrile (72 ml). Precipitate the product, filter it and dry it to give (I-43) (22.3 g, 83%).

[0967] 1 H NMR(400MHz, DMSO-d6)δppm 9.02(d,2H)8.55-8.75(br s,3H)8.37(s,1H)7.68(t,1H)5.34(m,1H)3.20-4.40(br s,1H)1.63(d,3H).

[0968] LC-MS (Method 5): Retention time 0.27 min, m / z 191 [M+H] + ].

[0969] Step E: N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)- Preparation of 1,2,3-benzotriazine-4-amine (compound P.145)

[0970]

[0971] 6,8-bis(trifluoromethyl)-3H-1,2,3-benzotriazine-4-one (I-41, 129 mg, 0.45 mmol, 1 equivalent), (1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethylamine; 2,2,2-trifluoroacetic acid (I-43, 180 mg, 0.59 mmol, 1.3 equivalent) and N-ethyl-N-isopropyl-propyl-2-amine (0.325 ml, 1.86 mmol, 4.1 equivalent) were dissolved in dimethyl sulfoxide (4.5 ml).

[0972] After stirring for 5 minutes at room temperature, the mixture of benzotriazol-1-yloxy(tripyrrolidine-1-yl)phosphonium; hexafluorophosphate (662 mg, 1.27 mmol, 2.8 equivalences) was stirred for 16 h at room temperature. It was diluted with water (50 mL) and extracted with EtOAc (3 x 50 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Purification by silica gel rapid chromatography (ethyl acetate in cyclohexane) provided the desired product (P.145) (68 mg, 33% yield).

[0973] 1 H NMR(400MHz,DMSO-d6)δppm 9.64(d,J=7.0Hz,1H)9.34(s,1H)8.98(d,J=4.8Hz,2H)8.61(s,1H)8.17(s,1H)7.64(t,J=5.0Hz,1H)6.57(m,1H)1.82(d,J=7.0Hz,3H).

[0974] 19 F NMR (377MHz, DMSO-d6) δppm-58.5(s,3F)-61.2(s,3F).

[0975] LC-MS (Method 3) retention time 0.92 min, m / z 456 [M+H] + ].

[0976] Example 15: 3-Fluoro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- Preparation of bis(trifluoromethyl)quinoline-4-amine (compound P.176)

[0977]

[0978] Step A: N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoro) Preparation of (methyl)quinoline-4-amine (I-44)

[0979]

[0980] Sodium hydride (60% by mass, 13.2 mg, 0.33 mmol, 1.5 equivalents) was placed in a dry vial and cooled to 0°C. A solution of N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (P.5 Example 1, 100 mg, 0.22 mmol, 1 equivalent) in tetrahydrofuran (0.88 mL) was added. After stirring for 5 minutes, iodomethane (20.8 μl, 0.33 mmol, 1.5 equivalents) was added, and the mixture was stirred at 25°C for 3.5 h. The mixture was quenched with saturated NH4Cl solution (5 mL) and diluted with water (20 mL). It was extracted with ethyl acetate (3 x 20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The desired product (I-44) (41 mg, 40%) was obtained by purification using silica gel rapid chromatography (ethyl acetate in cyclohexane).

[0981] 1 H NMR (400MHz, CDCl3) δppm 8.65(d,J=5.1Hz,1H)8.43(s,1H)8.20(d,J=1.1Hz,1H)8.09(s,1H)8.08(d,J=4.8Hz,2H)6.93 (t, J = 4.8 Hz, 1H) 6.68 (d, J = 5.1 Hz, 1H) 6.25 (q, J = 7.0 Hz, 1H) 2.88 (s, 3H) 2.08 (d, J = 7.0 Hz, 3H).

[0982] LC-MS (Method 3) retention time 1.04 min, m / z 468 [M+H] + ].

[0983] Step B: 3-Fluoro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis Preparation of (trifluoromethyl)quinoline-4-amine (compound P.176)

[0984]

[0985] N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (30 mg, 0.064 mmol, 1 equivalent) was dissolved in acetonitrile (321 μl). Selectfluor (23.7 mg, 0.064 mmol, 1 equivalent) was added and stirred at room temperature for 17 h. A second batch of Selectfluor (12 mg, 0.032 mmol, 0.5 equivalent) was added and stirred for another 7 h. A third batch of Selectfluor (12 mg, 0.032 mmol, 0.5 equivalent) was added and stirred for 17 h. The solution was quenched with MeOH, filtered, and purified on RP18 silica. P.176 (18 mg, 58% yield).

[0986] 1 H NMR (400MHz, CDCl3) δppm 8.68 (d, J = 3.7Hz, 1H) 8.51 (s, 1H) 8.15 (s, 3H) 8.11 (s, 1H) 6.91 (t, J = 4.8Hz, 1H) 6.03 (q, J = 7.0Hz, 1H) 3.09 (d, J = 3.7Hz, 3H) 2.02 (d, J = 7.0Hz, 3H).

[0987] 19 F NMR (377MHz, CDCl3) δppm-60.52(s,3F)-62.51(s,3F)-133.71(s,1F).

[0988] LC-MS (Method 3) retention time 1.10 min, m / z 487 [M+H] + ].

[0989] Example 16: 3-Chloro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8- Preparation of bis(trifluoromethyl)quinoline-4-amine (P.181)

[0990]

[0991] Step A: 3-Chloro-N-methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis (trifluoromethyl)quinoline- 4 -Amine (compound P.181) ) Preparation

[0992]

[0993] N-Methyl-N-[(1S)-1-(2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-6,8-bis(trifluoromethyl)quinoline-4-amine (Example 15, I-44, 41 mg, 0.088 mmol, 1 equivalent) was dissolved in dichloromethane (0.88 mL) and cooled to -19 °C. N-chlorosuccinimide (13 mg, 0.096 mmol, 1.1 equivalent) was added and the mixture was stirred at -19 °C for 1 h. It was then stirred at room temperature for 20 h. Additional N-chlorosuccinimide (13 mg, 0.096 mmol, 1.1 equivalent) and dimethyl sulfoxide (31.5 μL) were added. Complete conversion was achieved after 17 h. The mixture was concentrated under reduced pressure and purified by rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product P.181 (14 mg, 32% yield).

[0994] 1 H NMR(600MHz,DMSO-d6,120℃)δppm 8.86 (s, 1H) 8.41 (d, J = 4.7Hz, 2H) 8.24 (s, 1H) 8.13 (s, 1H) 7.24 (t, J = 4.8Hz, 1H) 5.91 (q, J = 7.0Hz, 1H) 3.15 (s, 3H) 1.86 (d, J = 6.9Hz, 3H).

[0995] LC-MS (Method 3) retention time 1.14 min, m / z 502 [M+H + ].

[0996] Example 17: 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino] ] [Ethyl]-1, Preparation of 2,4-triazol-1-yl]pyridine-3-thiocarboxamide (P.190)

[0997]

[0998] Step A: Preparation of 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridine-3-carboxylonitrile (I-45)

[0999]

[1000] Tert-butyl N-[(1S)-1-[2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate (I-34, 75% purity, 13 g, 31 mmol, 1 equivalent) was dissolved in dichloromethane (195 ml) and trifluoroacetic acid (78 ml, 982 mmol, 31.7 equivalent) was added. The mixture was stirred at 25 °C for 1 h. The reaction mixture was concentrated under reduced pressure.

[1001] Dichloromethane (195 ml) was added to the crude oil and alkalized with saturated Na₂CO₃ solution. The aqueous layer was extracted with dichloromethane (2 × 200 ml). The combined organic layers were dried over anhydrous Na₂SO₄ and evaporated under reduced pressure to give a white solid. It was washed with TBME and dried under reduced pressure to give (I-45) (7 g, 87%, 88% purity).

[1002] 1 H NMR (400MHz, DMSO-d6) δppm 9.06 (s, 1H) 8.55 (d, 1H) 8.23 ​​(s, 1H) 8.06 (d, 1H) 4.67-4.87 (m, 1H) 1.47 (d, 3H).

[1003] Step B: 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-tri Preparation of [1-azolyl]pyridine-3-carboxynitrile (I-46)

[1004]

[1005] 4-Chloro-6,8-bis(trifluoromethyl)quinazoline (I-9 Example 2, 4.0 g, 13.3 mmol, 1 equivalent) was dissolved in acetonitrile (40 mL). 6-[5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridin-3-carboxynitrile (I-45, 85% purity, 3.35 g, 13.3 mmol, 1 equivalent) and cesium carbonate (8.67 g, 26.6 mmol, 2 equivalent) were added and the mixture was stirred at 25 °C for 16 h. The reaction mixture was poured into ice-water and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated under reduced pressure, then purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to provide the desired product (I-46) (5.1 g, 80%).

[1006] 1 H NMR(400MHz,DMSO-d6)δppm 9.47(d,1H)9.27(s,1H)9.04(s,1H)8.58(d,1H)8.44(s,1H)8.36(s,1H)8.21(s,1H)8.09(d,1H)6.42(quin.,1H)1.77(d,3H).

[1007] LC-MS (Method 5) retention time 1.59 min, m / z 479 [M+H] + ].

[1008] Step C: 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino] ] [Ethyl]-1, Preparation of 2,4-triazol-1-yl]pyridine-3-carboxylonitrile (I-47)

[1009]

[1010] A sealable tube was filled with 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]amino]ethyl]-1,2,4-triazol-1-yl]pyridin-3-carboxylonitrile (I-46, 294 mg, 0.61 mmol, 1 equivalent), acetonitrile (4.92 mL), cesium carbonate (601 mg, 1.84 mmol, 3 equivalents), and iodomethane (77.3 μl, 1.23 mmol, 2 equivalents). The vial was sealed and heated to 50 °C for 16 hours. After cooling to 25 °C, it was diluted with water (10 mL) and extracted with ethyl acetate (3 × 10 mL). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, and concentrated under reduced pressure. It was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to give the desired product (I-47) (250 mg, 83%).

[1011] 1 H NMR (400MHz, CDCl3) δppm 8.55 (s, 1H) 8.35 (d, J = 5.9Hz, 2H) 8.24 (s, 1H) 8.11-8.20 (m, 2H) 8.03 (s, 1H) 6.88 (q, J = 6.97Hz, 1H) 1.96 (d, J = 6.97Hz, 3H).

[1012] 19 F NMR (377MHz, CDCl3) δppm-61.33(s,3F)-62.39(s,3F).

[1013] LC-MS (Method 3) retention time 1.11 min, m / z 493 [M+H] + ].

[1014] Step D: 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino] ] [Ethyl]-1, Preparation of 2,4-triazol-1-yl]pyridine-3-thiocarboxamide (P.190)

[1015]

[1016] 6-[5-[(1S)-1-[[6,8-bis(trifluoromethyl)quinazolin-4-yl]-methyl-amino]ethyl]-1,2,4-triazol-1-yl]pyridin-3-carboxynitrile (I-47, 300 mg, 0.61 mmol, 1 equivalent) was dissolved in pyridine (2.4 mL) and ammonium sulfide solution (20 wt%, 1.04 mL, 3.05 mmol, 5 equivalent) was added. The reaction mixture was stirred at 25 °C for 16 h. It was diluted with water and extracted with ethyl acetate (4 times). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. It was purified by silica gel rapid chromatography (ethyl acetate in cyclohexane) to give (P.190) (78 mg, 24%).

[1017] 1 H NMR (400MHz, DMSO-d6) δppm 10.04 (br s, 1H) 9.65 (br s, 1H) 8.55 (s, 1H) 8.27-8.41 (m, 5H) 7.91 (d, J = 8.44Hz, 1H) 6.76 (br d, J = 6.85Hz, 1H).

[1018] 19 F NMR (377MHz, DMSO-d6) δppm-59.74(s,3F)-60.75(s,3F).

[1019] LC-MS (Method 4) retention time 1.12 min, m / z 528 [M+H] + ].

[1020] Table P: Examples of compounds having Formula I

[1021]

[1022]

[1023]

[1024]

[1025]

[1026]

[1027]

[1028]

[1029]

[1030]

[1031]

[1032]

[1033]

[1034]

[1035]

[1036]

[1037]

[1038]

[1039]

[1040]

[1041]

[1042]

[1043]

[1044]

[1045]

[1046]

[1047]

[1048]

[1049]

[1050]

[1051]

[1052]

[1053]

[1054]

[1055]

[1056]

[1057]

[1058]

[1059]

[1060]

[1061]

[1062]

[1063]

[1064]

[1065]

[1066]

[1067]

[1068]

[1069]

[1070]

[1071]

[1072]

[1073]

[1074]

[1075]

[1076]

[1077] Table of compounds having formula III(i):

[1078]

[1079]

[1080]

[1081]

[1082] Table of compounds having formula V(i):

[1083]

[1084]

[1085]

[1086]

[1087] Table of compounds having formula VII(i):

[1088]

[1089]

[1090]

[1091] 1. 1H NMR (400MHz, DMSO) δppm 1.57 (d, J=6.97Hz, 3H) 4.65 (td, J=14.67, 3.30Hz, 2H) 5.10 (q, J=6.85Hz, 1H) 6.34-6.67 (m, 1H) 7.47 (br s,2H)8.30(s,1H)8.85(s,2H);

[1092] 2. 1H NMR (400MHz, DMSO d6) δppm 1.57-1.62(d,3H)5.02-5.33(q,1H)7.28-7.72(t,1H)7.73-7.99(s,2H)8.25-8.44(s,1H)8.93-9.10(s,2H);

[1093] 3. 1H NMR (400MHz, DMSO) δppm 1.54(d,J=6.97Hz,3H)5.04(d,J=6.60Hz,1H)6.97-7.16(m,2H)7.91-7.99(m,1H)8.06-8.15(m,1H)8.65(d,J=2.93Hz,1H); 19F NMR(377MHz,DMSO)δppm-126.89(s,1F)

[1094] The activity of the compositions according to the invention can be significantly broadened and adapted to general conditions by adding other insecticidal, acaricidal, and / or fungicidal ingredients. Mixtures of compounds of Formula I with other insecticidal, acaricidal, and / or fungicidal ingredients can also have additional unexpected advantages, which can be described more broadly as synergistic activity. For example, better plant tolerance, reduced phytotoxicity, control of insects at different developmental stages, or better behavior during their production (e.g., during grinding or mixing, during storage, or during use).

[1095] Here, the appropriate active ingredients are representative of the following categories of active ingredients: organophosphorus compounds, nitrophenol derivatives, thiourea, juvenile hormones, formamidin, benzophenone derivatives, ureas, pyrrole derivatives, carbamates, pyrethroids, chlorinated hydrocarbons, acylurea, pyridylmethylene amino derivatives, macrolides, neonicotinoids, and Bacillus thuringiensis preparations.

[1096] Preferred mixtures are those of compounds having Formula I and the following active substances (the abbreviation "TX" means "a compound selected from the compounds defined in Tables D-1 to D-66 and Table P"):

[1097] The auxiliary agent is selected from the following group of substances: petroleum (alias) (628) + TX.

[1098] Insect-controlling active substances selected from abamectin + TX, miticide quinoline + TX, acetamiprid + TX, acetamiprid + TX, flufenoxuron + TX, acynonapyr + TX, difenoconazole + TX, afralanar + TX, pyrethroid + TX, propargite + TX, α-cypermethrin + TX, cypermethrin + TX, sulfadiazine + TX, cypermethrin + TX, triazophos + TX, chlorpyrifos + TX, benzopyrimoxan + TX, β-cypermethrin + TX, β-cypermethrin + TX, bifenazate + TX, bifenthrin + TX, chlorfenapyr + TX, bio-allethrin + TX, bio-allethrin S-cyclopentyl isomer + TX, and bio-benzalofop-p-ethyl. Ester + TX, Diflubenzuron + TX, Broflanilide + TX, Brofenoxam + TX, Bromothion-Ethyl + TX, Thiamethoxam + TX, Butanil + TX, Thiamethoxam + TX, Carbaryl + TX, Sevin + TX, Thiamethoxam + TX, Butylcarbofuran + TX, Batan + TX, CAS No.: 1472050-04-6+TX, CAS No.: 1632218-00-8+TX, CAS No.: 1808115-49-2+TX, CAS No.: 2032403-97-5+TX, CAS No.: 2044701-44-0+TX, CAS No.: 2128706-05-6+TX, CAS No.: 2249718-27-0 (or CAS No.)2246757-58-2)+TX, CAS No.: 907187-07-9+TX, Chlorantraniliprole+TX, Chlordane+TX, Bromoxynil+TX, Cyclopyralid+TX, Clenbuterol+TX, Cloethocarb+TX, Thiamethoxam+TX, 2-Chlorophenyl N-methylcarbamate (CPMC)+TX, Benzoate+TX, Bromoxynil+TX, Cyclopyralid+TX, Cyclobutrifluram+TX, Pyrethroids+TX, Ethoxyfen+TX, Cyclopyrafen+TX, Cyclobutrifluram+TX, Pyrethroids+TX, Cyclopyralid+TX, Cyclopyrafen+TX, Cyclobutrifluram+TX TX, cypermethrin + TX, cyhalodiamide + TX, deltamethrin + TX, cypermethrin + TX, cypermethrin + TX, cyproflanilide + TX, cyromazine + TX, deltamethrin + TX, acaricide + TX, chlorpyrifos + TX, dibromide + TX, dibromide + TX, flufenoxuron + TX, diflubenzuron + TX, difenoconazole + TX, difenoconazole + TX, difenoconazole + TX, chlorpyrifos + TX, emamectin benzoate + TX, d-enyryl acetate + TX, ε-momfluo rothrin+TX, ε-methoxybenzylfluthrin+TX, cypermethrin+TX, ethion +TX, acetamiprid +TX, etoxazole +TX, chlorpyrifos +TX, quinfenoxam +TX, pendimethalin +TX, fenitrothion +TX, sec-butylcarbide +TX, fenthiocarb +TX, fenoxycarb +TX, cypermethrin +TX, fenpyroxymate +TX, fenpropathrin +TX, fenthion +TX, cypermethrin +TX, fenpropathrin +TX, fipronil +TX, flometoquin +TX, flonicamid +TX, pyrimethanil +TX, fluazaindolizine +TX, pyridaben +TX, Flufenoxuron +TX, Flufenoxuron +TX, Flucitrinum +TX, Fludioxonil +TX, Flufenoxuron +TX, Flufenoxuron +TX, Pyrimethanil +TX, Trifluralin +TX, Butenpyram +TX, Fluhexafon +TX, Flucypermethrin +TX, Flupentiofenox +TX, Flupyrimin +TX, Fluralaner +TX, Flumetamide +TX, Fluxametamide +TX, Thiazolylphosphine +TX, γ-Trifluralin +TX, Gossyplure TM+TX, imidacloprid +TX, chlorfenapyr +TX, chlorfenapyr +TX, Halfenprox +TX, heptafluthrin +TX, thiamethoxam +TX, flufenoxuron +TX, imidacloprid +TX, imidacloprid +TX, indoxacarb +TX, iodomethacin +TX, iprodione +TX, isocycloseram +TX, isopyram +TX, ivermectin +TX, κ-bifenthrin +TX, κ-hyperflufenoxuron +TX, lambda-cyhalothrin +TX, chlorfenapyr +TX, cyfluthrin +TX, metaldehyde +TX, methoxyfenozide +TX, methomyl +TX, methomyl +TX, methoxyfenozide +TX, Methoxyfenozide +TX, Dimethoate +TX, Carbendazim +TX, Acaricide +TX, Momfluorothrin +TX, Dimethoate +TX, Nicofluprole +TX, Acetaminophen +TX, Nitrothiamethoxam +TX, Omethoate +TX, Cypermethrin +TX, Oxazosulfyl +TX, Parathion-ethyl +TX, Permethrin +TX, Dimethoate +TX, Sciroctone +TX, Piperazine +TX, Piperazine +TX, Pyrimethanil-ethyl +TX, Polyhexylvirus +TX, Pyrimethanil +TX, Profenofos +TX, Profenofos +TX, Cypermethrin +TX, Acaricide +TX, Acaricide +TX, Profenofos +TX, Profenofos +TX, Profenofos +TX, Profenofos +TX, Profenofos +TX Protrifenbute + TX, Pyflubumide + TX, Pymetrozine + TX, Pyrafluprole + TX, Pyridaben + TX, Acetaminophen + TX, Pyrifluquinazon + TX, Pyrifen + TX, Pyrifen + TX, Pyrifen + TX, Pyrifen + TX, Pyrifen + TX, Fenoxam + TX, Cypermethrin + TX, Sarolaner + TX, Selamectin + TX, Flumethrin + TX, Spinosad + TX, Spinosad + TX, Spiropidion + TX Spirotetramat + TX, Sulfadiazine + TX, Tebufenozide + TX, Pyridaben + TX, Tebupirimiphos + TX, Heptamethrin + TX, Dimethoate + TX, Tetrachlorantraniliprole + TX, Tetradiphon + TX, Aspergillus + TX, Tebufenozide + TX, Acaricide + TX, Flufenoxuron + TX, θ-Cypermethrin + TX, Thiamethoxam + TX, Thiamethoxam + TX, Cypermethrin + TX, Thiamethoxam + TX, Thiamethoxam + TX, Thiamethoxam + TX, Dichlorvos + TX, Methionine + TX, Pyralid + TX, Tioxazafen + TX, Azoxystrobin + TX, Toxaphene + TXTetrabromopyrethrin + TX, Tetrafluorobenzyl + TX, Azoxystrobin + TX, Triazophos + TX, Trichlorfon + TX, Toxamethonium + TX, Trichlorfon + TX, Triflumezopyrim + TX, Tyclopyrazoflor + TX, ζ-Cypermethrin + TX, Algae extract and glycoyl-derived fermentation products + TX, Algae extract and glycoyl-derived fermentation products (including urea + TX, amino acids + TX, potassium and molybdenum, and EDTA chelated manganese) + TX, Algae extract and fermented plant products + TX, Algae extract and fermented plant products (including plant hormones + TX, vitamins + TX, EDTA chelated copper + TX, zinc + TX, and iron + TX), Azadirachtin + TX, Bacillus aizawai + TX, Bacillus chitinosporus AQ746 (NRRL registration number B-21) 618)+TX, Bacillus sturdier +TX, Bacillus kurstaki +TX, Bacillus mycosis fungoides AQ726 (NRRL accession B-21664)+TX, Bacillus pumilus (NRRL accession B-30087)+TX, Bacillus pumilus AQ717 (NRRL accession B-21662)+TX, Bacillus species AQ178 (ATCC accession 53522)+TX, Bacillus species AQ175 (ATCC accession 55608)+TX, Bacillus species AQ177 (ATCC accession 55609)+TX, Bacillus subtilis (unspecified)+TX, Bacillus subtilis AQ153 (ATCC accession 55614) +TX, Bacillus subtilis AQ30002 (NRRL Registry No. B-50421) +TX, Bacillus subtilis AQ30004 (NRRL Registry No. B-50455) +TX, Bacillus subtilis AQ713 (NRRL Registry No. B-21661) +TX, Bacillus subtilis AQ743 (NRRL Registry No. B-21665) +TX, Bacillus thuringiensis AQ52 (NRRL Registry No. B-21619) +TX, Bacillus thuringiensis BD#32 (NRRL Registry No. B-21530) +TX, Bacillus thuringiensis Kurstaki subsp. BMP 123+TX, Beauveria bassiana +TX, D-limonene +TX, granulovirus +TX, Harpin +TX, bollworm nucleopolyhedrovirus +TX, corn armyworm nucleopolyhedrovirus +TX, tobacco shoot armyworm nucleopolyhedrovirus +TX, Australian bollworm nucleopolyhedrovirus +TX, Metarhizium species +TX, Muscodor albus 620 (NRRL registry number 30547) +TX,Muscodor roseus A3-5 (NRRL registration number 30548) +TX, neem-based products +TX, *Paecilomyces rosé* +TX, *Paecilomyces lilacinus* +TX, *Paecilomyces serrata* +TX, *Paecilomyces serrata* +TX, *Paecilomyces punctata* +TX, *Paecilomyces mycoides* +TX, *Paecilomyces thornei* +TX, *Paecilomyces* +TX, p-cymene +TX, diamondback moth granulovirus +TX, diamondback moth nucleopolyhedrovirus +TX, polyhedrovirus +TX, pyrethrum +TX, QRD 420 (terpene blend) +TX, QRD 452 (terpene blend) +TX, QRD 460 (terpene blend) + TX, *Saponaria spp.* + TX, *Rhodococcus spherulites* AQ719 (NRRL registry number B-21663) + TX, *Fall Armyworm* nucleopolyhedrovirus + TX, *Streptomyces flavus* (NRRL registry number 30232) + TX, *Streptomyces* species (NRRL registry number B-30145) + TX, terpene blend + TX, and *Verticillium* species;

[1099] Algicide selected from the following groups of substances: bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX, copper sulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX, dichlorophenol (232)+TX, fentin (295)+TX, fentin (347)+TX, quicklime [CCN]+TX, sodium mancozeb (566)+TX, quinoclamine (714)+TX, quinonamid (1379)+TX, simazine (730)+TX, tin triphenylacetate (IUPAC name) (347) and tin triphenyl hydroxide (IUPAC name) (347)+TX;

[1100] The anthelmintic is selected from the group of substances consisting of: abamectin (1)+TX, chlorfenapyr (1011)+TX, cyclobutyral+TX, doxorubicin (alias) [CCN]+TX, emamectin (291)+TX, emamectin benzoate (291)+TX, irinotecan (alias) [CCN]+TX, ivermectin (alias) [CCN]+TX, milbemycin oxime (alias) [CCN]+TX, moxicillin (alias) [CCN]+TX, piperazine [CCN]+TX, slakine (alias) [CCN]+TX, spinosad (737) and thiophanate (1435)+TX;

[1101] Bird killers selected from the following groups of substances: chloralose (127) + TX, isodrin (1122) + TX, fenthion (346) + TX, pyridine-4-amine (IUPAC name) (23) and strychnine (745) + TX;

[1102] Bactericides selected from the following groups of substances: 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX, 4-(quinoxalo-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX, 8-hydroxyquinoline sulfate (446)+TX, bromonitrile (97)+TX, copper dioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name) (169)+TX, cresol [CCN]+TX, dichlorophenol (232)+TX, dipyrithione (1105)+TX, doxycycline (1112)+TX, fenaminosulfonate (1144)+TX, formaldehyde (404)+TX, mercaptophenone ( (Alternative names) [CCN]+TX, Kasugamycin (483)+TX, Kasugamycin hydrochloride hydrate (483)+TX, Di(dimethyldithiocarbamate) nickel (IUPAC name) (1308)+TX, Nitropyrin (580)+TX, Octhilinone (590)+TX, Oxytetracycline (606)+TX, Oxytetracycline (611)+TX, Potassium hydroxyquinoline sulfate (446)+TX, Probenazole (658)+TX, Streptomycin (744)+TX, Streptomycin sesquisulfate (744)+TX, Phthalate (766)+TX, and Thimerosal (alternative name) [CCN]+TX;

[1103] Biological reagents, selected from the following groups of substances: Cotton Brown Leaf Roller GV (alias) (12)+TX, *Agrobacterium radiata* (alias) (13)+TX, *Amblyseius spp.* (alias) (19)+TX, Celery Noctuid Moth NPV (alias) (28)+TX, *Anagrus atomus* (alias) (29)+TX, *Aphelinus adominalis* (alias) (33)+TX, Cotton Aphid Parasitic Wasp (Aphidius colemani) (alias) (34)+TX, Aphidoletes aphidimyza (alias) (35)+TX, Alfalfa Silver-striped Noctuid Moth NPV (alias) (38)+TX, *Bacillus firmus* (alias) (48)+TX, *Bacillus sphaericus* Neide)(scientific name)(49)+TX, Bacillus thuringiensis Berliner)(scientific name)(51)+TX, Bacillus thuringiensis subsp. aizawai)(scientific name)(51)+TX, Bacillus thuringiensis subsp. israelensis)(scientific name)(51)+TX, Bacillus thuringiensis subsp. japonensis)(scientific name)(51)+TX, Bacillus thuringiensis subsp. kurstaki)(scientific name)(51)+TX, Bacillus thuringiensis subsp. truncatella)(scientific name)(51)+TX, Bacillus thuringiensis subsp.tenebrionis (scientific name) (51)+TX, Beauveria bassiana (synonym) (53)+TX, Beauveria brongniartii (synonym) (54)+TX, Chrysoperla carnea (synonym) (151)+TX, Cryptolaemus montrouzieri (synonym) (178)+TX, Codling moth GV (synonym) (191)+TX, Dacnusa sibirica (synonym) (212)+TX, Diglyphusisaea (synonym) (254)+TX, Encarsia formosa (scientific name) (293)+TX, Eretmocerus eremicus (alias) (300)+TX, Grainworm NPV (alias) (431)+TX, Heterorhabditis bacteriophora and H. megidis (alias) (433)+TX, Hippodamia convergens (alias) (442)+TX, Leptomastixdactylopii (alias) (488)+TX, Macrophorus caliginosus (alias) (491)+TX, Cabbage moth NPV (alias) (494)+TX, Metaphycus helvolus (alias) (522)+TX, Metarhizium anisopliae var. acridum (scientific name) (523)+TX, Metarhizium anisopliae var. anisopliae (scientific name) (523)+TX, Neodiprionsertifer NPV and Neodiprionsertifer (N.lecontei)NPV (synonyms) (575)+TX, Species of the genus *Lecontei* (synonyms) (596)+TX, *Paecilomyces fumosoroseus* (synonyms) (613)+TX, *Phytoseiulus persimilis* (synonyms) (644)+TX, *Spodopteraexigua multicapsid nuclear polyhedrosis virus* (scientific name) (741)+TX, *Steinernema bibionis* (synonyms) (742)+TX, *Steinernema carpocapsae* (synonyms) (742)+TX, *Steinernema glaseri* (synonyms) (742)+TX, *Steinernema rubescens* (synonyms) (742)+TX, *Steinernema glaseri* (synonyms) (742)+TX, *Steinernema rubescens* riobrave)(synonyms)(742)+TX, Steinernemariobravis(synonyms)(742)+TX, Steinernema scapterisci(synonyms)(742)+TX, Steinernema spp.(synonyms)(742)+TX, Trichogramma spp.(synonyms)(826)+TX, Typhlodromus occidentalis(synonyms)(844) and Verticillium lecanii(synonyms)(848)+TX;

[1104] Soil disinfectant, selected from the following group of substances: iodomethane (IUPAC name) (542) and bromomethane (537) + TX;

[1105] Chemical sterilizing agents are selected from the following groups of substances: apholate [CCN]+TX, bisazir [CCN]+TX, busulfan [CCN]+TX, diflubenzuron (250)+TX, dimatif [CCN]+TX, hemel [CCN]+TX, hempa [CCN]+TX, metepa [CCN]+TX, methyl thiophanate... Methiotepa [CCN]+TX, methylapholate [CCN]+TX, morzid [CCN]+TX, penfluron (alias) [CCN]+TX, tepa [CCN]+TX, thiohempa (alias) [CCN]+TX, thiotepa (alias) [CCN]+TX, tratamine (alias) [CCN], and urethaneimine (alias) [CCN]+TX;

[1106] Insect pheromones are selected from the following groups of substances: (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol (IUPAC name) (222)+TX, (E)-tetadecarbon-4-en-1-yl acetate (IUPAC name) (829)+TX, (E)-6-methylheptane-2-en-4-ol (IUPAC name) (541)+TX, (E,Z)-tetradecane-4,10-dien-1-yl acetate (IUPAC name) (779)+TX, (Z)-dodecane-7-en-1-yl acetate (IUPAC name) (285)+TX, (Z)-hexadecane-11-enal (IUPAC name) (436)+TX, (Z)-hexadecane-11-en-1-yl acetate (IUPAC name) (437)+T X, (Z)-hexadec-13-en-11-yn-1-yl acetate (IUPAC name) (438)+TX, (Z)-eicosero-13-en-10-one (IUPAC name) (448)+TX, (Z)-tetradec-7-en-1-al (IUPAC name) (782)+TX, (Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX, (Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX, (7E,9Z)-dodec-7,9-dien-1-yl acetate (IUPAC name) (283)+TX, (9Z,11E)-tetradec-9,11-dien-1-yl acetate (IUPAC name) (780)+TX, (9Z,12E)-tetradec-9,12-Dien-1-ylacetate (IUPAC name) (781)+TX, 14-Methyloctadec-1-ene (IUPAC name) (545)+TX, 4-Methylnon-5-ol and 4-Methylnon-5-one (IUPAC name) (544)+TX, alpha-multistriatin (alias) [CCN]+TX, brevicomin (alias) [CCN]+TX, codlelure (alias) [CCN]+TX, codlelure (alias) [CCN]+TX, codlelure (alias) mone)(alias)(167)+TX, cuelure)(alias)(179)+TX, disparlure)(277)+TX, dodecano-8-en-1-yl acetate (IUPAC name))(286)+TX, dodecano-9-en-1-yl acetate (IUPAC name))(287)+TX, dodecano-8+TX, 10-dien-1-yl acetate (IUPAC name))(284)+TX, dominicalure(alias)[CCN]+TX, ethyl 4-methyloctanoate (IUPA) C Name)(317)+TX, Eugenol (Alias) [CCN]+TX, Frontalin (Alias) [CCN]+TX, Gossyplure (Alias) (420)+TX, Grandlure (421)+TX, Grandlure I (Alias) (421)+TX, Grandlure II (Alias) (421)+TX, Grandlure III (Alias) (421)+TX, Grandlure IV (Alias) (421)+TX, Hexalure [CCN]+TX, ipsdienol (alias) [CCN]+TX, ipsenol (alias) [CCN]+TX, japonilure (alias) (481)+TX, lineatin (alias) [CCN]+TX, litlure (alias) [CCN]+TX, looplure (alias) [CCN]+TX, medlure (alias) [CCN]+TX, megatomoic acid (alias) [CCN]+TX, methyl eugenol (alias) (540)+TX, muscalure (563)+TX, octadec-2,13-dien-1-yl acetate (IUPAC name) (588)+TX, octadec-3,13-Dien-1-ylacetate (IUPAC name) (589)+TX, Orfralure (alias) [CCN]+TX, Oryctalure (alias) (317)+TX, Ostramone (alias) [CCN]+TX, Siglure (CCN)+TX, Sordidin (alias) (736)+TX, Sulcatol (Alias) [CCN]+TX, tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, Mediterranean fruit fly attractant (839)+TX, Mediterranean fruit fly attractant A (alias) (839)+TX, Mediterranean fruit fly attractant B1 (alias) (839)+TX, Mediterranean fruit fly attractant B2 (alias) (839)+TX, Mediterranean fruit fly attractant C (alias) (839) and trunc-call (alias) [CCN]+TX;

[1107] Insect repellents selected from the group consisting of the following substances: 2-(octylthio)ethanol (IUPAC name) (591)+TX, butopyronoxyl (933)+TX, butoxy (polypropylene glycol) (936)+TX, dibutyl adipate (IUPAC name) (1046)+TX, dibutyl phthalate (1047)+TX, dibutyl succinate (IUPAC name) (1048)+TX, DEET [CCN]+TX, dimethyl carbate [CCN]+TX, dimethyl phthalate [CCN]+TX, ethylhexanediol (1137)+TX, hexourea [CCN]+TX, methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX, oxamate [CCN], and picaridin [CCN]+TX;

[1108] Molluscicides selected from the group consisting of the following substances: di(tributyltin)oxide (IUPAC name) (913)+TX, bromoacetamide [CCN]+TX, calcium arsenate [CCN]+TX, chlorpyrifos (999)+TX, copper acetylacetate [CCN]+TX, copper sulfate (172)+TX, triphenyltin (347)+TX, ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX, cypermethrin (530)+TX, niclosamide (576)+TX, niclosamide-ethanolamine (576)+TX, pentachlorophenol ( 623)+TX, sodium pentachlorophenoxide (623)+TX, tazimcarb (1412)+TX, thiamethoxam (799)+TX, tributyltin oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX, triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide (IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX;

[1109] Nematicides selected from the following groups of substances: AKD-3088 (compound code) + TX, 1,2-dibromo-3-chloropropane (IUPAC / Chemical Abstracts name) (1045) + TX, 1,2-dichloropropane (IUPAC / Chemical Abstracts name) (1062) + TX, 1,2-dichloropropane and 1,3-dichloropropene (IUPAC name) (1063) + TX, 1,3-dichloropropene (233) + TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide (IUPAC / Chemical Abstracts name) Abstract Name)(1065)+TX, 3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX, 5-methyl-6-thio-1,3,5-thiadiazin-3-ylacetic acid (IUPAC name) (1286)+TX, 6-isopentenylaminopurine (synonym) (210)+TX, avermectin (1)+TX, acetaminophen [CCN]+TX, basil (15)+TX, aldicarb (16)+TX, aldicarb (863)+TX, AZ60541 (compound code) + TX, benclothiaz [CCN] + TX, benomyl (62) + TX, butylpyridaben (synonym) + TX, chlorpyrifos (109) + TX, carbofuran (118) + TX, carbon disulfide (945) + TX, thiocarbofuran (119) + TX, chloropicrin (141) + TX, chlorpyrifos (145) + TX, chlorpyrifos (999) + TX, cyclobutyral + TX, cytokinin (synonym) (2 10)+TX, Dazomet (216)+TX, DBCP (1045)+TX, DCIP (218)+TX, Diamidafos (1044)+TX, Diamidafos (1051)+TX, Dicliphos (alias)+TX, Dimethoate (262)+TX, Dolaxidine (alias) [CCN]+TX, Emamectin (291)+TX, Emamectin Benzoate (291)+TX, Irinokine (alias) [CCN]+TX, Dimethoate (312)+TX, Dibromoethane (316)+TX, Benzylphosphonate (326)+TX, Fenpyrad (synonym)+TX, Fenpyrophosphonate (1158)+TX, Thiazolium Phosphate (408)+TX, Butylthionyl Phosphate (1196)+TX, Furfural (synonym) [CCN]+TX, GY-81 (research code) (423)+TX, Phosphorus oxychloride [CCN]+TX, Iodomethane (IUPAC name) (542)+TX, Isamidofos (1230)+TX , Chlorpyrifos (1231)+TX, Ivermectin (synonym) [CCN]+TX, Kinetin (synonym) (210)+TX, Methyl phosmet (1258)+TX, Viprox (519)+TX, Viprox potassium salt (synonym) (519)+TX, Viprox sodium salt (519)+TX, Methyl bromide (537)+TX, Methyl isothiocyanate (543)+TX, Milbex oxime (synonym) [CCN]+TX, Moxifloxacin (synonym) [CCN]+TX, MyrotheciumVerrucaria) Composition (Alias) (565)+TX, NC-184 (Compound Code)+TX, chlorpyrifos (602)+TX, phorate (636)+TX, phosphatidylcholine (639)+TX, phosphatidylcholine [CCN]+TX, chlorpyrifos (Alias)+TX, silachlor (Alias) [CCN]+TX, spinosad (737)+TX, tert-butylcarbate (Alias)+TX, terbufos (773)+TX, tetrachlorothiophene (IUPAC / Chemical) Abstract Name)(1422)+TX, thiafenox (synonym)+TX, nematicide (1434)+TX, triazophos (820)+TX, triazophos (synonym)+TX, xylenol [CCN]+TX, YI-5302 (compound code) and zeatin (synonym) (210)+TX, fluensulfone [318290-98-1]+TX, fluopyram+TX;

[1110] Nitrification inhibitors selected from the group consisting of: potassium ethyl xanthate [CCN] and nitrapyrin (580) + TX;

[1111] Plant activator selected from the following group of substances: acibenzolar (6)+TX, acibenzo-S-methyl (6)+TX, probenazole (658) and Reynoutria sachalinensis extract (synonym) (720)+TX;

[1112] Rodenticides selected from the following groups of substances: 2-isovaleryl indan-1,3-dione (IUPAC name) (1246) + TX, 4-(quinoxalo-2-ylamino)benzenesulfonamide (IUPAC name) (748) + TX, α-chlorool [CCN] + TX, aluminum phosphide (640) + TX, antagonist (880) + TX, arsenic trioxide (882) + TX, barium carbonate (891) + TX, daridin (912) + TX, bromadiolone (89) + TX, bromadiolone ( Including α-bromadiolone (92) + TX, bromadiolone (92) + TX, calcium cyanide (444) + TX, chloralose (127) + TX, chloramine (140) + TX, cholecalciferol (850) + TX, chlorfenapyr (1004) + TX, cyproheptadine (1005) + TX, cyproheptadine (175) + TX, cyproheptadine (1009) + TX, cyproheptadine (246) + TX, cyproheptadine (249) + TX, cyproheptadine (273) + TX, calciferol (301) + TX. Fluroxypyr (357)+TX, Fluoroacetamide (379)+TX, Fluroxypyridine (1183)+TX, Fluroxypyridine hydrochloride (1183)+TX, γ-HCH (430)+TX, HCH (430)+TX, Hydrogen cyanide (444)+TX, Iodomethane (IUPAC name) (542)+TX, Lindane (430)+TX, Magnesium phosphide (IUPAC name) (640)+TX, Methyl bromide (537)+TX, Rattrium (1318)+TX, Ratphos (1 336)+TX, Phosphine (IUPAC name) (640)+TX, Phosphine [CCN]+TX, Warfarin (1341)+TX, Potassium Arsenite [CCN]+TX, Warfarin (1371)+TX, Onion Glycoside (1390)+TX, Sodium Arsenite [CCN]+TX, Sodium Cyanide (444)+TX, Sodium Fluoroacetate (735)+TX, Strychnine (745)+TX, Thallium Sulfate [CCN]+TX, Warfarin (851) and Zinc Phosphide (640)+TX;

[1113] Synergists selected from the group consisting of the following substances: 2-(2-butoxyethoxy)ethyl piperitate (IUPAC name) (934)+TX, 5-(1,3-benzodioxane-5-yl)-3-hexylcyclohex-2-enone (IUPAC name) (903)+TX, farnesol with nerolidol (alias) (324)+TX, MB-599 (research code) (498)+TX, MGK 264 (research code) (296)+TX, piperonyl butoxide (649)+TX, piperonal (1343)+TX, propyl isomer (1358)+TX, S421 (research code) (724)+TX, sesamex (1393)+TX, sesasmolin (1394) and sulfoxide (1406)+TX;

[1114] Animal repellents, which are composed of the following substances: anthraquinone (32)+TX, chloralose (127)+TX, copper naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon (227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine (422)+TX, guazatine (422)+TX, guanidine octate (422)+TX, cypermethrin (530)+TX, pyridine-4-amine (IUPAC name) (23)+TX, silane (804)+TX, trimethacarb (840)+TX, zinc naphthenate [CCN] and zinc thiram (856)+TX;

[1115] The antiviral agent is selected from the following group of substances: Imanin (also known as CCN) and Ribavirin (also known as CCN) + TX;

[1116] The wound protectant is selected from the following group of substances: mercuric oxide (512) + TX, octhilinone (590) and methyl thiophanate (802) + TX;

[1117] Bioactive substances selected from 1,1-bis(4-chlorophenyl)-2-ethoxyethanol + TX, 2,4-dichlorophenylbenzenesulfonate + TX, 2-fluoro-N-methyl-N-1-naphthylacetamide + TX, 4-chlorophenylphenyl sulfone + TX, acetamiprid + TX, aldicarb + TX, cypermethrin + TX, phosmet + TX, methamidophos + TX, ammonium oxalate + TX, amitraz + TX, chlorpyrifos + TX, arsenic trioxide + TX, azobenzene + TX, azophos + TX, benomyl + TX, benzyl benzoate + TX, bifenthrin + TX, bromopyridaben + TX, bromothion + TX, bromopyridaben + TX, bromothion + TX, bromopyridaben + TX, bromothion + TX, bromopyridaben Acaricide + TX, Thiamethoxam + TX, Butanone + TX, Butanone Sulfonate + TX, Butylpyridinium + TX, Calcium Polysulfide + TX, Camphene + TX, Chlorpyrifos + TX, Trithion + TX, Acaricide + TX, Acaricide + TX, Acaricide + TX, Acaricide + TX, Acaricide Hydrochloride + TX, Acaricide + TX, Acaricide + TX, Acaricide + TX, Difenoconazole + TX, Ethyl Acetate + TX, Chlormebuform + TX, Difenoconazole + TX, Propyl Acetate + TX, Chlorpyrifos + TX, Ciprofloxacin I + TX, Ciprofloxacin II + TX, Ciprofloxacin + TX, Clofenoxam + TX, Phoxim + TX, Clomidon + TX, Phoxim + TX TX, Thiazol + TX, Fruitworm Phosphate + TX, DCPM + TX, DDT + TX, Demeton-S-methyl + TX, Demeton-O + TX, Demeton-O-methyl + TX, Demeton-S+TX, Demeton-S-methyl + TX, Demeton-S-methylsulfon + TX, Antibacterial + TX, Dichlorvos + TX, Dichlorvos + TX, Acaricide + TX, Mefenoxam + TX, Dinex + TX, Dinex-diclexine + TX, Difenoconazole-4 + TX, Difenoconazole-6 +TX, acaricides including: chlorpyrifos +TX, amyl nitrate +TX, octyl nitrate +TX, nitrate +TX, dichlorvos +TX, sulfadiazine +TX, disulfiram +TX, DNOC +TX, dofenapyn +TX, dofenapyn +TX, phosmet +TX, phosmet +TX, ethirimol +TX, fenbutatin +TX, fenthion +TX, fenthiocarb +TX, fenpyrad +TX, pyridaben +TX, pyridaben +TX, fentrifanil +TX, flufenoxuron +TX, flufenoxuron +TX, fenfluramide +TX, fentrifanil +TX, fenfluramide +TX, fenfluramide +TX, fenfluramide +TX, FMC 1137 +TX, fenfluramide +TX, fenfluramide hydrochloride +TX, formparanate +TX, γ-HCH +TX, fenfluramide +TXBenzyl ether + TX, cetylcyclopropane carboxylate + TX, methamidophos + TX, jasmine ester I + TX, jasmine ester II + TX, iodophos + TX, lindane + TX, propiconazole + TX, pymetrozine + TX, dithiamethoxam + TX, methiophene + TX, chlorfenapyr + TX, methyl bromide + TX, methamidophos + TX, milbemime + TX, propanil + TX, phosmet + TX, methamidophos + TX, moxifloxacin + TX, dibromophos (naled) + TX, 4-chloro-2-(2-chloro-2-methyl-propyl)-5-[(6-iodo-3-pyridyl)methoxy]pyridazine-3-one + TX, flufenoxuron + TX, nicotinamide + TX, cyanamide + TX, cyanamide 1:1 zinc chloride complex TX + phosmet, omethoate + phosmet, sulfadiazine + phosmet, pp'-DDT + TX, parathion + TX, permethrin + TX, fenthion + TX, phosmet + TX, thiophanate-methyl + TX, phosphamidon + TX, polychloroterpenes + TX, polynactins + TX, prochloraz + TX, pymetrozine + TX, propoxur + TX, ethiophanate-methyl + TX, phosmet + TX, pyrethroid + TX, pyrethroid + TX, pyrethroid + TX, pyrethroid + TX, pyridaben + TX, pyrethroid + TX, pyrimethanil + TX, pyrethroid + TX, quinalphos + TX, quintiofos + TX, R-1 492+TX, glyphosate+TX, rotenone+TX, octamethrin+TX, chlorpyrifos+TX, silachlor+TX, thiophanate-methyl+TX, SSI-121+TX, sulphurin+TX, fipronil+TX, thiophanate-methyl+TX, sulfur+TX, flufenoxam+TX, t-flufenoxam+TX, TEPP+TX, terbufos+TX, tetrachlorfon+TX, chlorfenapyr+TX, thiafenoxam+TX, chlorpyrifos+TX, methyl methamidophos+TX, chlorpyrifos+TX, thiamethoxam+TX, chlorpyrifos+TX, fenpyroxetine+TX, triazophos+TX, triazolium+TX, trichlorfon+TX, chlorpyrifos+TX, chlorpyrifos+TX TX, vaniliprole + TX, bethoxazin + TX, copper dioctanoate + TX, copper sulfate + TX, cybutryne + TX, dichloronaphthoquinone + TX, dichlorophenol + TX, cypermethrin + TX, triphenyltin + TX, quicklime + TX, sodium mancozeb + TX, cymoxanil + TX, quinoline + TX, simazine + TX, triphenyltin acetate + TX, triphenyltin hydroxide + TX, pyrazine + TX, piperazine + TX, thiophanate-methyl + TX, chloralose + TX, fenthion + TX, pyridine-4-amine + TX, strychnine + TX, 1-hydroxy-1H-pyridine-2-thione + TX, 4-(quinoxalo-2-ylamino)benzenesulfonamide + TX,8-Hydroxyquinoline sulfate + TX, bromonitol + TX, copper hydroxide + TX, cresol + TX, dipyrithione + TX, dodexamethasone + TX, sodium dichloroisocyanurate + TX, formaldehyde + TX, mercuroquinone + TX, kasugamycin + TX, kasugamycin hydrochloride hydrate + TX, nickel di(dimethyldithiocarbamate) + TX, trichloromethylpyridine + TX, octathione + TX, oxorubicin + TX, potassium hydroxyquinoline sulfate + TX, thiabendazole + TX, streptomycin + TX, streptomycin sesquisulfate + TX, chlorothalonil + TX, thimerosal + TX, cotton brown belt moth GV + TX, *Agrobacterium radiata* + TX, *Amblyseius spp.* + TX, celery cutworm NPV + TX, *Anagrus atomus* + TX, *Aphelinus abdominalis* + TX, cotton aphid parasitoid wasp * *Aphidoletes aphidimyza* + TX, *Alfalfa Silver-striped Noctuidae* NPV + TX, *Bacillus sphaericus Neide* + TX, *Beauveria brongniartii* + TX, *Chrysoperla carnea* + TX, *Cryptolaemus montrouzieri* + TX, *Codling moth* GV + TX, *Dacnusa sibirica* + TX, *Diglyphus isaea* + TX, *Encarsia formosa* + TX, *Eretmocerus eremicus* + TX, *Heterorhabditis* bacteriophora and H. megidis +TX, Hippodamia convergens +TX, Leptomastix dactylopii +TX, Macrorolophus caliginosus +TX, cabbage looper NPV +TX, Metaphycus helvolus +TX, Metarhizium anisopliae var. acridum +TX, Metarhizium anisopliae var. anisopliae +TX, Neodiprion sertifer NPV and N. lecontei NPV +TX,Species of the genus *Sterculia* + TX, *Paecilomyces fumosoroseus* + TX, *Phytoseiulus persimilis* + TX, *Steinernema bibionis* + TX, *Steinernema carpocapsae* + TX, *Steinernema glaseri* + TX, *Steinernema riobrave* + TX, *Steinernema riobravis* + TX, *Steinernema scapterisci* + TX, species of the genus *Steinernema* + TX, species of the genus *Trichogramma* + TX, *Typhlodromus* occidentalis)+TX, Verticillium lecanii+TX, apholate+TX, bisazir+TX, busulfan+TX, dimatif+TX, hemel+TX, hempa+TX, metepa+TX, methiotepa+TX, methyl pyrazophosphorus apholate + TX, morzid + TX, penfluron + TX, tepa + TX, thiohempa + TX, thiohempa + TX, tratamine + TX, urethaneimine + TX, (E)-dec-5-en-1-yl acetate and (E)-dec-5-en-1-ol + TX, (E)-tetrate-4-en-1-yl acetate + TX, (E)-6-methylhept-2-en-4-ol + TX, (E,Z)-tetradec-4,10-dien-1-yl acetate + TX, (Z)-dodec-7-en-1-yl acetate + TX, (Z)-hexadecyl C11-enal + TX, (Z)-hexadec-11-en-1-yl acetate + TX, (Z)-hexadec-13-en-11-yn-1-yl acetate + TX, (Z)-eicosero-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, (7E,9Z)-dodec-7,9-dien-1-yl acetate + TX, (9Z,11E)-tetradec-9,11-dien-1-yl acetate + TX, (9Z,12E)-tetradec-9,12-dien-1-yl acetate + TX14-Methyloctadec-1-ene + TX, 4-Methylnon-5-ol and 4-Methylnon-5-one + TX, α-polystyrin + TX, western pine bark beetle aggregate pheromone + TX, dodecadienol (codlelure) + TX, codlemone + TX, cuelure + TX, nonadecane oxide + TX, dodecadien-8-en-1-yl acetate + TX, dodecadien-9-en-1-yl acetate + TX, dodecadien-8 + TX, 10-dien-1-yl acetate + TX, dominicalure + TX, ethyl 4-methyloctanoate + TX, eugenol + TX, southern pine bark beetle aggregate pheromone (f Rontalin + TX, Grandlure + TX, Grandlure I + TX, Grandlure II + TX, Grandlure III + TX, Grandlure IV + TX, Hexalure + TX, Ipsdienol + TX, ...

Claims

1. Compounds of formula Iaa or Iab: wherein R1 is hydrogen, methyl, ethyl, cyanomethyl, methoxymethyl, cyclopropyl-methyl, allyl, propargyl, benzyloxycarbonyl, or benzyl; R 2a is hydrogen, halogen, C3-C4 cycloalkyl, C3-C4 cycloalkylcarbonyl, C3-C4 cycloalkyl-C1-C2 alkyl optionally substituted with one to two substituents selected from oxo, halogen, C1-C3 alkyl and C1-C3 haloalkyl, C1-C3 haloalkyl, C1-C3 haloalkylsulfanyl, C1-C3 haloalkylsulfonyl, C1-C3 alkoxy, C1-C3 haloalkoxy, or CN; R 2b is chloro, fluoro, bromo, iodo, difluoromethyl, trifluoromethyl, trifluoromethylsulfanyl or trifluoromethylsulfonyl; R3 is methyl, and Q1 is selected from Q aa To Q ag and Q ba To Q bf : or an agrochemically acceptable salt or stereoisomer of the compound of formula Iaa or Iab.

2. A compound according to claim 1, wherein the stereoisomers are enantiomers.

3. A composition comprising a compound as defined in claim 1 or 2, one or more adjuvants and diluents and optionally one or more other active ingredients.

4. A method for combating and controlling insects, mites, nematodes or molluscs for non-therapeutic purposes, the method comprising applying an insecticidal, acaricidal, nematicidal or molluscicidal effective amount of a compound as defined in claim 1 or 2 or a composition as defined in claim 3 to a pest, a location of a pest, or a plant susceptible to attack by a pest.

5. A method for protecting plant propagation materials from attack by insects, mites, nematodes or molluscs, the method comprising treating the propagation materials or the site in which the propagation materials are planted with an effective amount of a compound as defined in claim 1 or 2 or a composition as defined in claim 3.

6. Use of a compound as defined in claim 1 or 2 or a composition as defined in claim 3 for the preparation of a medicament for controlling parasites in or on an animal in need thereof.

7. A compound having formula XI(i) XI(i) Wherein A1, A2 and A3 are independently N or CH, provided that no more than two of the three are N; A4 and A5 are both CH; And R1, R 2a , R 2b and R3 is as defined in claim 1.

8. A compound having formula XIV (i) XIV(i) wherein A1, A2 and A3 are independently N or CH, provided that no more than two of the three are N; A4 and A5 are both CH; And R1, R 2a , R 2b and R3 is as defined in claim 1.

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