CN117715523A - Methods for controlling diamide-resistant pests and compounds thereof - Google Patents

Abstract

A method for combating and controlling diamide resistant insects to effect the following: (i) Reducing damage to plants, the method comprising applying to the insects, to the locus of the insects, or to plants susceptible to attack by the insects an effective amount of a compound having formula (I); or (ii) protecting plant propagation material, the method comprising treating the propagation material or the locus in which the propagation material is grown with an effective amount of a compound of formula (I); wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, pairs of those compounds of formula IEnantiomers, tautomers and N-oxides may be used as insecticides.

Description

Methods for controlling diamide-resistant pests and compounds thereof

The present invention relates to methods of controlling diamide-resistant pests by using certain pesticidally active (particularly insecticidally active) diamide compounds. Further, the invention also relates to certain pesticidally active (in particular insecticidal) diamide compounds, processes for their preparation, compositions comprising those compounds, and their use for controlling animal pests (including arthropods and in particular insects or representatives of the order lepidoptera, in particular diamide-resistant lepidoptera insects).

Bicyclic diamide (or bisamide) derivatives having insecticidal action are known and described, for example, in WO 2007/093402, WO 2009/010260 and WO 2009/024341.

Bisamide insecticidal derivatives have been widely used for over ten years and some insect populations have developed a level of resistance such that they are not readily adequately controlled by commercially available bisamides. The result of this evolution is that higher doses of protective agents have to be used and/or that the protection of crops may be inadequate.

Diamide insecticides target the Raney base receptor in insects and result in the depletion of intracellular calcium stores (Ebbinghaus-Kintscher et al 2006; sattelle, cordova and Cheek 2008; cordova et al 2006). Commercially available diamides can be categorized into two classes: the only representatives of which are fipronamide and anthranilamide include chlorantraniliprole, cyantraniliprole, cycloxaprid and tetrazolium-chlorantraniliprole. Other examples of phthalic acid carboxamides and anthranilamides are cyhalodiamide, fluchlorantraniliprole and tetrachlorethamide. All diamides share the same mode of action and are therefore grouped in IRAC MoA group 28.

Diamides represent a rapidly growing class of insecticides introduced to the market since the commercialization of neonicotinoids (Sparks and Nauen 2015; richardson et al 2020; troczka et al 2017) and are extremely valuable insect control agents, especially because they exhibit little or no cross-resistance to the older insecticidal class, which presents significant resistance problems. However, reports on insect resistance to diamide insecticides are increasing.

Thus, the increased resistance of such insects to diamide insecticides poses a significant threat to the planting of many important crops, fruits and vegetables, and there is a need to find alternative insecticides that are capable of better controlling diamide resistant insects (e.g., to find insecticides that do not exhibit any cross resistance with diamides).

Resistance may be defined as "heritable changes in sensitivity of pest populations reflected in repeated failure of a product to achieve a desired level of control when that product is used for those pest species according to the label recommendations" (IRAC 2009).

Cross-resistance occurs when resistance to one insecticide imparts resistance to another insecticide via the same biochemical mechanism. This may occur within the group of insecticide chemicals or between groups of insecticide chemicals. Cross-resistance can occur even if resistant insects have never been exposed to one of the chemical classes of insecticides.

Two of the main mechanisms for diamide resistance include:

(i) Target site resistance, whereby resistance is associated with substitution of one or more amino acids in the insecticidal target protein (i.e., the ranitidine receptor); and

(ii) Metabolic resistance, such as enhanced oxidative detoxification of diamides due to over-expression of cytochrome P450 monooxygenase (P450), or conjugation to diamides due to over-expression of UDP-dependent glycosyltransferase (UGT).

Target site resistance has been described in a variety of lepidopteran species including: plutella xylostella (Plutella xylostella) (Troczka et al 2012; steinbach et al 2015; guo et al 2014), tomato leaf miner (Tuta absorber) (Roditakis et al 2017; zimmer et al 2019), spodoptera frugiperda (Spodoptera frugiperda) (Bolzan et al 2019), spodoptera exigua (Spodoptera exigua) (Zuo et al 2020,2017), chilo suppressalis (Chilo suppressalis) (Yao et al 2017; yang et al 2017). Parallel evolution with two mutations frequently described between species, i.e., I4970M and G4946E (plutella xylostella numbering), can also be observed for diamide resistance (Richardson et al 2020), similar to that described for target site resistance of other insecticides, e.g., organic chlorides affecting GABA receptors (ffrench-Constant et al 1998). However, this does not exclude that mutations at different positions in the target site may cause a high level of diamide resistance.

Cytochrome P450 monooxygenases are an important metabolic system involved in the detoxification (i.e.modification) of xenobiotics in stage I (Dermauw, van Leeuwen and Feyereisen2020; bard 2000). Thus, P450 monooxygenases play an important role in insecticide resistance. P450 monooxygenases have such a surprisingly large array of metabolizable substrates, since numerous P450 species (about 26-261 species) are present in arthropod species and some P450 have a broad substrate specificity (Dermauw, van Leeuwen and Feyereisen 2020). Studies of monooxygenase mediated resistance have shown that resistance may be due to increased gene expression (quantitative) of one of the P450 genes involved in insecticide detoxification, and also to mutations in the gene itself that alter amino acid composition (qualitative) (Feyeresen, dermauw and Van Leeuwen 2015). Thus, metabolic cross-resistance mechanisms affect not only insecticides from a given class (e.g., neonicotinoids), but also what appears to be irrelevant. For example, cross-resistance relationships between neonicotinoids and pymetrozine in Bemisia tabaci (Bemisia tabaci) have been reported (Gorman et al 2010; nauen et al 2013).

In addition to cytochrome P450, other enzymes and transporter families (e.g., oxidases, hydrolases, transferases, and ABC transporters) can also result in insecticide resistance (Dermauw and Van Leeuwen 2014; feyereen, dermauw and Van Leeuwen 2015; bass et al 2014). P450 and other oxidases, transferases and ABC transporters have been implicated in diamide resistance (Li et al 2017; mallott et al 2019; li et al 2018; shin et al 2021).

It is therefore highly desirable to find a class of compounds that provides better control over resistant insects.

It has now surprisingly been found that certain bicyclic diamide derivatives are better able to control diamide resistant insects as well as other related insects.

Accordingly, the present invention in a first aspect relates to a method for combating and controlling diamide resistant insects to effect the following:

(i) Reducing damage to plants, the method comprising applying to the insects, to a locus of the insects, or to plants susceptible to attack by the insects an effective amount of a compound of formula I and/or an agronomically acceptable salt, isomer, enantiomer, tautomer and/or N-oxide of a compound of formula I; or (b)

(ii) Protecting plant propagation material, the method comprising treating the propagation material or the locus where the propagation material is grown with an effective amount of a compound of formula I and/or an agronomically acceptable salt, isomer, enantiomer, tautomer and/or N-oxide of a compound of formula I;

wherein the compound of formula I is

Wherein the method comprises the steps of

A is O or S;

R ₁ is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Haloalkyl, or C ₃ -C ₆ Cycloalkyl;

G ₁ 、G ₂ and G ₃ And G ₁ And G ₃ The two carbon atoms attached together form a heteroaromatic or partially saturated ring system, wherein G ₁ 、G ₂ And G ₃ Selected from nitrogen, sulfur, oxygen and carbon, the bond between two consecutive G's being a single bond, a double bond or an aromatic bond, wherein at least one G represents nitrogen, sulfur or oxygen, and no more than two G's may be oxygen or sulfur, and where two G's are oxygen and/or sulfur they are separated by one carbon atom;

from G ₁ 、G ₂ 、G ₃ And the five-membered ring formed by the two carbon atoms to which they are attached is substituted with one to three groups independently selected from X1-Z, with the proviso that

X1 is a direct bond, Z is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, (C) ₁ -C ₆ Alkyl) C (=O), (C ₃ -C ₆ Cycloalkyl) C (=o), (C ₁ -C ₆ Alkoxy) C (=o), (C ₃ -C ₆ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkyl sulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, or C ₁ -C ₄ A haloalkylsulfonyl group; or X1 is C ₁ -C ₆ Alkyldiyl, Z is halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, (C) ₁ -C ₆ Alkyl) C (=O), (C ₃ -C ₆ Cycloalkyl) C (=o), (C ₁ -C ₆ Alkoxy) C (=o), (C ₃ -C ₆ Cycloalkoxy) C (=o), benzyl, halobenzyl Radical, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkyl sulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, C ₁ -C ₄ Haloalkyl sulfonyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₆ Cycloalkyl carbonyloxy;

R ₃ is phenyl, or a 6 membered heteroaromatic ring, each of which is unsubstituted or is one to three independently selected from R ₆ Is substituted by a substituent of (a);

R ₄ is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, C ₃ -C ₆ Cyanocycloalkyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, or X2-Y, wherein X2 is C ₁ -C ₆ Alkyldiyl or C ₁ -C ₆ Haloalkyl-di-and

y is cyano, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkylsulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, C ₁ -C ₄ Haloalkylsulfonyl, benzyloxy, halobenzyloxy, 5-or 6-membered heteroaromatic ring which is unsubstituted or is selected from one to three independently R ₇ Substituted, or 9-or 10-membered heteroaromatic bicyclic systems, which are not takenSubstituted or independently selected from one to three R ₇ Substitution;

R ₆ independently selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Haloalkylthio, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, (C) ₁ -C ₃ Alkyl) NHC (=o), (C ₁ -C ₃ Alkyl group ₂ NC(＝O)、(C ₃ -C ₆ Cycloalkyl) NHC (=o), and (C ₃ -C ₆ Cycloalkyl) (C) ₁ -C ₃ Alkyl) NC (=o);

R ₇ independently selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₆ Cycloalkyl, (C) ₁ -C ₃ Alkyl) NHC (=o), (C ₁ -C ₃ Alkyl group ₂ NC(＝O)、(C ₃ -C ₆ Cycloalkyl) NHC (=o), and (C ₃ -C ₆ Cycloalkyl) (C) ₁ -C ₃ Alkyl) NC (=o), phenyl (which may be one to three independently selected from halogen, cyano, C ₁ -C ₄ Alkyl, C ₁ -C ₃ Alkoxy and C ₁ -C ₃ Haloalkyl), and a 6 membered heteroaromatic ring (which may be substituted with one to three substituents independently selected from halogen, cyano, C ₁ -C ₄ Alkyl, C ₁ -C ₃ Alkoxy and C ₁ -C ₃ Halo substituent).

It has now further been found that certain novel bicyclic bisamide derivatives provide improved control of these bisamide resistant insects. Accordingly, a second aspect of the present invention relates to a compound of formula I as defined in the first aspect, provided that (I) when R ₃ R in the case of 3-chloro-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In the second aspectIn the examples of (1), the following compounds are excluded (i) when R ₃ R is monochloro-pyridin-2-yl ₄ Is CF (CF) ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ And (ii) when R ₃ Is mono-chloro-pyridin-2-yl and X1-Z is different from hydrogen, R ₄ Is OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the Preferably for both (i) and (ii), R ₃ Is monohalo-pyridin-2-yl, more preferably R for both (i) and (ii) ₃ Is a monohalo-pyridyl group, and is preferably a halogen,

by using the compounds of formula I according to each aspect of the invention, damage caused by diamide-resistant insects on plants, especially on plants and ornamental plants useful in agriculture, in horticulture and in forestry, or on organs such as fruits, flowers, leaves, stems, tubers or roots of such plants, and in some cases even on plant organs formed at a later point in time, is controlled, reduced.

Compound I having at least one basic center may for example form for example an acid addition salt with: strong mineral acids (e.g. mineral acids, such as perchloric acid, sulfuric acid, nitric acid, nitrous acid, phosphoric acid or hydrohalic acid), strong organic carboxylic acids (e.g. C, unsubstituted or substituted, for example, by halogen ₁ -C ₄ An alkanoic acid, for example acetic acid, such as a saturated or unsaturated dicarboxylic acid, for example oxalic acid, malonic acid, succinic acid, maleic acid, fumaric acid or phthalic acid, such as hydroxycarboxylic acid, for example ascorbic acid, lactic acid, malic acid, tartaric acid or citric acid, or such as benzoic acid), or an organic sulphonic acid (such as C which is unsubstituted or substituted, for example by halogen) ₁ -C ₄ Alkanesulfonic or arylsulfonic acids, for example methanesulfonic acid or p-toluenesulfonic acid). Compound I having at least one acidic group may form, for example, a salt with a base, for example a mineral salt, such as an alkali metal or alkaline earth metal salt, for example a sodium, potassium or magnesium salt; or with ammonia or an organic amine (such as morpholine, piperidine, pyrrolidine, mono-, di-or tri-lower alkylamine, for example ethylamine, diethylamine, triethylamine or dimethylpropylamine, or mono-, di-or tri-hydroxy lower alkylamine, for example monoethanolamine, diethanolamine or triethanolamine). In the appropriate caseIn addition, the corresponding internal salts can be formed. Preferred within the scope of the invention are agrochemically advantageous salts; however, the invention also covers salts which are disadvantageous for agrochemical use, for example salts which are toxic to bees or fish, and which are used, for example, for the isolation or purification of the free compounds I or their agrochemically usable salts. Due to the close relationship between the free form and the salt form of compound I, for the purposes of the present invention, free compound I or a salt thereof in the foregoing and in the following is understood to include the corresponding salt or free compound I, respectively, where appropriate. This applies analogously to the tautomers of compound I and its salts. In general, the free form is preferred in each case.

The N-oxide is an oxidized form of a tertiary amine or an oxidized form of a nitrogen-containing heteroaromatic compound. They are described, for example, in the books "Heterocholic N-oxides [ Heterocyclic N-oxides ]", CRC Press [ CRC Press ], boca Raton [ Bokaraton ]1991 by A.Albini and S.Pietra.

The compounds of formula I according to the invention also include hydrates which may form during salt formation.

As used herein, the term "C ₁ -C _n Alkyl "refers to a saturated straight or branched hydrocarbon group having 1 to n carbon atoms attached via any carbon atom, such as any of the following groups: methyl, ethyl, n-propyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2-dimethylpropyl, 1-ethylpropyl, n-hexyl n-pentyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl 1, 1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-dimethylbutyl, 2, 3-dimethylbutyl, 3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1, 2-trimethylpropyl, 1, 2-trimethylpropyl, 1-ethyl-1-methylpropyl, or 1-ethyl-2-methylpropyl.

As used herein, the term "C ₁ -C _n Haloalkyl "refers to a straight or branched saturated alkyl group having 1 to n carbon atoms attached via any one carbon atom (as mentioned above), wherein some of these groupsOr all hydrogen atoms may be replaced by groups independently selected from fluorine, chlorine, bromine and iodine, i.e., for example, any of the following groups: chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl 2-iodoethyl, 2-difluoroethyl, 2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2, 2-difluoroethyl 2, 2-dichloro-2-fluoroethyl, 2-trichloroethyl, pentafluoroethyl, 2-fluoropropyl 3-fluoropropyl group, 2-difluoropropyl group, 2, 3-difluoropropyl group, 2-chloropropyl group, 3-chloropropyl group 2, 3-dichloropropyl, 2-bromopropyl, 3-trifluoropropyl, 3-trichloropropyl 2, 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 "C ₁ -C ₂ Fluoroalkyl will mean C with 1,2, 3, 4 or 5 fluorine atoms ₁ -C ₂ An alkyl group, such as any of the following: difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-difluoroethyl 2, 2-trifluoroethyl, 1, 2-tetrafluoroethyl or pentafluoroethyl.

As used herein, the term "C ₁ -C _n Alkoxy "refers to a straight or branched saturated alkyl group (as mentioned above) having 1 to n carbon atoms attached via an oxygen atom, i.e., for example, any one of the following groups: methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy or 1, 1-dimethylethoxy. The term "halo C", as used herein ₁ -C _n Alkoxy "means C ₁ -C _n Examples of alkoxy groups in which one or more hydrogen atoms on the alkyl group are replaced by one or more identical or different halogen atoms include trifluoromethoxy, 2-fluoroethoxy, 3-fluoropropoxy, 3-trifluoropropoxy, 4-chlorobutoxy.

As used herein, the term "C ₃ -C _n Cycloalkyl "means a 3-n membered cycloalkyl group, such as cyclopropane, cyclobutane, cyclopentane and ringHexane.

As used herein, the term "C ₃ -C _n Halocycloalkyl "means C substituted by one or more halogen atoms which may be the same or different ₃ -C _n Cycloalkyl moieties.

As used herein, the term "C ₃ -C _n Cyanocycloalkyl "means C substituted with one or more cyano groups, preferably one cyano group ₃ -C _n Cycloalkyl moieties.

As used herein, the term "C ₁ -C _n Alkyldiyl "refers to a saturated straight or branched hydrocarbon group attached via two single bonds from one or more of its carbon atoms to two other groups, e.g., acting as a spacer between the two groups. Examples are methylene (or-CH ₂ (-) and ethylene (-CH) ₂ CH ₂ -)。

As used herein, the term "C ₁ -C _n Haloalkyl-di-groups "refer to C substituted with one or more halogen atoms which may be the same or different ₁ -C _n An alkanediyl moiety.

As used herein, the term "C ₃ -C _n Cycloalkyl carbonyloxy "means attached to carbonyloxy (C (O) ₂ ) A 3-n membered cycloalkyl group of the group, and the oxygen atom of the carbonyloxy group is attached to the remainder of the molecule. Similarly, as used herein, the term "C ₁ -C _n Alkylcarbonyloxy "refers to an alkyl group attached to carbonyloxy (C (O) ₂ ) An alkyl group of the group, and an oxygen atom of the carbonyloxy group is attached to the remainder of the molecule.

As used herein, the term "C ₁ -C _n Alkylsulfanyl "refers to C linked through a sulfur atom ₁ -C _n An alkyl moiety. Similarly, as used herein, the term "C ₁ -C _n Haloalkylthio "or" C ₁ -C _n Haloalkylsulfanyl "refers to C attached through a sulfur atom ₁ -C _n A haloalkyl moiety.

As used herein, the term "C ₁ -C _n Alkylsulfinyl "refers to a linkage through the sulfur atom of the S (=o) groupC of the junction ₁ -C _n An alkyl moiety. Similarly, as used herein, the term "C ₁ -C _n Haloalkyl sulfinyl "or" C ₁ -C _n Haloalkyl sulfinyl "refers to C linked through the sulfur atom of the S (=o) group ₁ -C _n A haloalkyl moiety.

As used herein, the term "C ₁ -C _n Alkylsulfonyl "means by S (=o) ₂ C linked to sulfur atoms of radicals ₁ -C _n An alkyl moiety. Similarly, as used herein, the term "C ₁ -C _n Haloalkylsulfonyl "or" C ₁ -C _n Haloalkylsulfonyl "refers to a compound obtained by reacting S (=o) ₂ C linked to sulfur atoms of radicals ₁ -C _n A haloalkyl moiety.

As used herein, the term "C ₂ -C _n Alkenyl "refers to a straight or branched alkenyl chain having from two to n carbon atoms and one or two double bonds, such as vinyl, prop-1-enyl, but-2-enyl.

As used herein, the term "C ₂ -C _n Alkynyl "refers to a straight or branched alkynyl chain having from two to n carbon atoms and one triple bond, such as ethynyl, prop-2-ynyl, but-3-ynyl.

Halogen or "halo" is typically fluoro, chloro, bromo or iodo. This applies correspondingly to halogens, e.g. haloalkyl, in combination with other meanings

The term "6 membered heteroaromatic" refers to a 6 membered aromatic ring having 1 to 3 carbon atoms independently replaced by nitrogen, sulfur, or oxygen. Examples are pyridinyl (or pyridinyl), pyridazinyl, pyrimidinyl, and pyrazinyl.

Examples of "5-or 6-membered heteroaromatic" refer to 5-or 6-membered aromatic rings having 1 to 3 carbon atoms independently replaced by nitrogen, sulfur, or oxygen. Examples are pyridinyl (or pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (e.g., 1,2, 4-triazolyl), furanyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl and thiadiazolyl.

Examples of "9-or 10-membered heteroaromatic" refer to 9-or 10-membered aromatic rings, which consist of two rings in which 1 to 4 carbon atoms are independently replaced by nitrogen, sulfur, or oxygen (these heteroatoms may be in one ring or distributed in both rings). Examples are purinyl, quinolinyl, cinnolinyl, quinoxalinyl, indolyl, indazolyl, benzimidazolyl, benzothienyl, benzoxazolyl, benzothiazolyl, imidazo [1,2-a ] pyridinyl, and imidazo [4,5-b ] pyridinyl.

As used herein, the term "control" refers to reducing the number of pests (or insects), eliminating pests, and/or preventing further pest damage such that damage to a plant or to a plant derived product is reduced. Insects cover all phases of the insect life cycle.

As used herein, the term "effective amount" refers to an amount of a compound or salt thereof that provides a desired effect upon single or multiple applications.

The staggered lines as used herein, for example in Ya1 to Ya17, represent the connection/attachment points to the remainder of the compound.

The effective amount is readily determined by one skilled in the art by using known techniques and by observing results obtained in similar circumstances. In determining an effective amount, a number of factors are considered, including but not limited to: the type of plant or derivative product to be applied; the pests to be controlled and their life cycle; the particular compound administered; type of application; and other related conditions.

In a preferred embodiment of each aspect of the invention, the compound having formula I is represented by formula Ia

Wherein R is ₁ 、R ₃ 、R ₄ 、G ₁ 、G ₂ 、G ₃ X1 and Z are as defined in the first aspect.

In a further preferred embodiment of each aspect of the invention, the compound of formula I is represented by formula Ib, ic, id, ie, if or Ig

Wherein R is ₁ 、R ₃ 、R ₄ X1 and Z are as defined in the first aspect.

As listed below, embodiments according to the present invention are provided.

In an embodiment of each aspect of the invention, A is

A. Sulfur; or (b)

B. Oxygen.

In an embodiment of each aspect of the invention, G ₁ 、G ₂ And G ₃

A. (i) nitrogen, nitrogen and carbon, respectively, or (ii) nitrogen, nitrogen and nitrogen, respectively, or (iii) oxygen, carbon and oxygen, respectively; or (b)

B. Nitrogen, nitrogen and carbon, respectively; or (b)

C. Nitrogen, nitrogen and nitrogen, respectively; or (b)

D. Oxygen, carbon and oxygen, respectively.

In embodiments of each aspect of the invention, X1-Z

A. Independently selected from X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, and X1 is C ₁ -C ₃ Alkyldiyl and Z is halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₄ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, C ₁ -C ₃ Haloalkyl sulfonyl, C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy; or (b)

B. Independently selected from X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, and X1 is methylene and Z is halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₄ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, C ₁ -C ₃ Haloalkyl sulfonyl, C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy; or (b)

C. Independently selected from X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy; or (b)

D. Independently selected from X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano; or (b)

E. Independently selected from X1 is a direct bond and Z is hydrogen, halogen, or benzyl; or (b)

F. Independently selected from X1 is a direct bond and Z is hydrogen, fluoro, or benzyl.

In embodiments of each aspect of the invention, R ₁ Is that

A. Hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Haloalkyl, or C ₃ -C ₄ Cycloalkyl; or (b)

B. Halogen, or C ₁ -C ₃ An alkyl group; or (b)

C. Methyl, F, cl, br, or I; or (b)

D. Methyl, cl, or Br; or (b)

E. Methyl or chlorine.

In embodiments of each aspect of the invention, R ₃ Is that

A. Phenyl, or a 6 membered heteroaromatic ring, each independently selected from R by one to three ₆ Is substituted by a substituent of (a); or (b)

B.6 membered heteroaromatic rings each independently selected from R by one to three ₆ Is substituted by a substituent of (a); or (b)

C. A pyridine ring, which is unsubstituted or one to three are independently selected from R ₆ Is substituted by a substituent of (a); or (b)

D. A pyridine ring, one or two of which are independently selected from halogen, cyano, and C ₁ -C ₃ Substituent substitution of alkyl; or (b)

E. A pyridine ring substituted with one or two substituents independently selected from chlorine, bromine, iodine, cyano, and methyl; or (b)

F. A pyridine ring substituted with one or two substituents independently selected from chlorine, bromine, and iodine; or (b)

G. A pyridine ring substituted with one or two substituent chlorides; or (b)

H. Pyridin-2-yl ring substituted with one or two substituents chloro; or (b)

3-chloro-pyridin-2-yl ring or 3, 5-dichloro-pyridin-2-yl ring.

In embodiments of each aspect of the invention, R ₄ Is that

A. Hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y; or (b)

B. Halogen, C ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y; or (b)

C. Trifluoromethyl, bromo, chloro, methoxy, difluoromethoxy, fluoromethoxy, or X2-Y; or (b)

D. Trifluoromethyl; or (b)

E. Bromine; or (b)

F. Chlorine; or (b)

G. Methoxy; or (b)

H. Difluoromethoxy; or (b)

I. Trifluoromethoxy; or (b)

J.X2-Y。

In an embodiment of each aspect of the invention,

A. (i) When R is ₃ R in the case of 3-chloro-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the Or (b)

B. (i) When R is ₃ R in the case of 3-halo-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-halo-2-pyridinyl and X1-Z are different from hydrogen, R ₄ Not OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the Or (b)

C. (i) When R is ₃ R in the case of 3-halo-2-pyridinyl ₄ Not halogen, trifluoromethyl, difluoromethyl, methoxy, 2-trifluoroethoxy, or trifluoromethoxy; and (ii) when R ₃ Is 3-halo-2-pyridinyl and X1-Z are different from hydrogen, R ₄ Not difluoromethoxy; or (b)

D. (i) When R is ₃ R in the case of halo-2-pyridinyl ₄ Not halogen, trifluoromethyl, difluoromethyl, methoxy, 2-trifluoroethoxy, or trifluoromethoxy; and (ii) when R ₃ R when is halo-2-pyridinyl and X1-Z are different from hydrogen ₄ Not difluoromethoxy

E. When R is ₃ R in the case of 3-halo-2-pyridinyl ₄ Not halogen, C ₁ Haloalkyl, C ₁ Haloalkoxy or C ₁ An alkoxy group; or (b)

F. When R is ₃ R in the case of halo-2-pyridinyl ₄ Not halogen, C ₁ Haloalkyl, C ₁ Haloalkoxy or C ₁ An alkoxy group;

in an embodiment of each aspect of the invention, X2 is

A.C ₁ -C ₃ Alkyldiyl, or C ₁ -C ₃ A haloalkadiyl group; or (b)

B.CH ₂ Or CF (CF) ₂ The method comprises the steps of carrying out a first treatment on the surface of the Or (b)

C.CH ₂ 。

In an embodiment of each aspect of the invention, Y is

A. Cyano, C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, C ₃ -C ₄ Halogenated cycloalkyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ HaloalkylsulfanesRadicals, C ₁ -C ₃ Haloalkyl sulfinyl, C ₁ -C ₃ Haloalkylsulfonyl, benzyloxy, halobenzyloxy, 5-or 6-membered heteroaromatic ring, which is unsubstituted or one to three independently selected from R ₇ Substituted with groups of (2), or 9-or 10-membered heteroaromatic bicyclic ring systems, unsubstituted or substituted with one to three groups independently selected from R ₇ Is substituted by a group of (2); or (b)

B. Cyano, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, C ₃ -C ₄ Halogenated cycloalkyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkylsulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, C ₁ -C ₃ Haloalkylsulfonyl, benzyloxy, halobenzyloxy, 5-or 6-membered heteroaromatic ring, which is unsubstituted or one to three independently selected from R ₇ Substituted with groups of (2), or 9-or 10-membered heteroaromatic bicyclic ring systems, unsubstituted or substituted with one to three groups independently selected from R ₇ Is substituted by a group of (2); or (b)

C.C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, halobenzyloxy, 5-or 6-membered heteroaromatic ring which is unsubstituted or one to three independently selected from R ₇ Substituted with groups of (2), or 9-or 10-membered heteroaromatic bicyclic ring systems, unsubstituted or substituted with one to three groups independently selected from R ₇ Is substituted by a group of (2); or (b)

D.C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or any one of Ya to Yj; or (b)

E. Selected from Ya to Yj; or (b)

F. Selected from Ya to Yh; or (b)

Yb, yc, yd, ye, yf, yg, or Yh; or (b)

Yb, yc, yd, ye or Yg, or Yh, wherein, independently of Y, R ₇ Selected from chlorine, bromine, fluorine, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl; or (b)

I. Selected from Ya1 to Ya17; or (b)

J. Selected from Ya1 to Ya9; or (b)

K. Selected from Ya1 to Ya6, and Ya9.

In embodiments of each aspect of the invention, R ₆

A. Independently selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Haloalkylthio, C ₁ -C ₃ Alkoxy, and C ₁ -C ₃ Haloalkoxy groups; or (b)

B. Independently selected from halogen, cyano, and C ₁ -C ₃ An alkyl group; or (b)

C. Independently selected from halogen; or (b)

D. Chlorine.

In embodiments of each aspect of the invention, R ₇

A. Independently selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₆ Cycloalkyl, substituted by one or more members selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Alkoxy, and C ₁ -C ₃ Phenyl substituted by a haloalkyl group, and optionally substituted by one or more groups selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Alkoxy, and C ₁ -C ₃ A haloalkyl group-substituted pyridyl group; or (b)

B. Halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₆ Cycloalkyl and substituted by chlorine, bromine, trifluoromethyl or difluoromethylPhenyl of (2); or (b)

C. Halogen, C ₁ -C ₃ Haloalkyl, C ₃ -C ₆ Cycloalkyl and phenyl substituted with chloro, bromo, trifluoromethyl or difluoromethyl; or (b)

D. Chlorine, bromine, fluorine, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl.

Thus, the present invention makes it possible to obtain compounds of formula I having substituents A, R as defined above in all combinations/arrangements ₁ 、R ₃ 、R ₄ 、G ₁ 、G ₂ 、G ₃ X1 and Z. Thus, for example, compounds having formula I wherein a is the first aspect (i.e., a is oxygen or sulfur) may be obtained; g ₁ 、G ₂ And G ₃ Is embodiment a (i.e., (i) nitrogen, and carbon, respectively, or (ii) nitrogen, and nitrogen, respectively, or (iii) oxygen, carbon, and oxygen, respectively); r is R ₁ Is example D (i.e., methyl, cl, or Br); r is R ₃ Is embodiment F (i.e., a pyridine ring substituted with one or two substituents independently selected from chlorine, bromine, and iodine); r is R ₄ Is example C (i.e., trifluoromethyl, bromo, chloro, methoxy, difluoromethoxy, fluoromethoxy, or X2-Y); wherein X1-Z are embodiment B (i.e., X1-Z are one to three substituents independently selected from the group consisting of X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, and X1 is methylene and Z is halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₄ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, C ₁ -C ₃ Haloalkyl sulfonyl, C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy); and X2 is embodiment C (i.e., X2 is methylene) and Y is embodiment D (i.e., Y is C) ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or any of Ya to Yj, wherein R ₇ Having embodiment B (i.e., R ₇ Is halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₆ Cycloalkyl, and phenyl substituted with chloro, bromo, trifluoromethyl, and difluoromethyl).

In embodiments of each aspect of the invention, the insect is a class 28 IRAC insecticidehttps://irac- online.org>moa-classification) Those that are resistant, such insecticides act on the Raney receptor of the insect-such insecticides are commonly referred to as diamide or phthalimide insecticides.

In embodiments, the compound having formula I controls insects that exhibit resistance to at least one compound selected from chlorantraniliprole, cyantraniliprole (cycloaniprole), chlorflufenamide, tetrachlorantraniliprole, tetrazolium chlorflufenamide, flubendiamide and cyhalodiamide.

Insects have developed target site resistance and have, for example, mutations, i.e., at least one of I4970M and G4946E (switzerland woodstar numbering). However, the skilled person does not exclude that mutations at different positions in the target site may also cause a high level of diamide resistance.

The diamide resistant insect is preferably from the order lepidoptera.

Preferred species are plutella xylostella (Troczka et al 2012; steinbach et al 2015; guo et al 2014), tomato leaf miner (Roditakis et al 2017; zimmer et al 2019), spodoptera frugiperda (Bolzan et al 2019), beet armyworm (Zuo et al 2020,2017), chilo suppressalis (Yao et al 2017; yang et al 2017).

In an embodiment of the first aspect, the method for combating and controlling diamide-resistant insects is in a defined plant area/field, wherein the ratio of diamide-resistant insects to their corresponding sensitive lines is greater than 1:20 (based on the number of insects), preferably greater than 1:10, in particular greater than 1:5.

In an embodiment of the first aspect, the compound having formula I controls diamide resistant insects better than the secondary amide analogue of the compound having formula I. The improvement in control may be greater than 20%, preferably greater than 30%, more preferably greater than 40%, and most preferably greater than 50%. The improvement in control is evaluated at the same level, for example at 5 ppm.

In an embodiment of the first aspect, the method for combating and controlling diamide resistant insects is by applying to insect-susceptible plants an effective amount of a compound having formula I; or by treating the propagation material with an effective amount of a compound of formula I.

In an embodiment, the compounds of formula I are represented by compounds of formulae Ia, ib, ic, id, ie, if and Ig, wherein the corresponding substituents are as defined for formula I in the first aspect.

In an embodiment of the first aspect of the invention, the compound of formula Ia has as R ₁ Or C ₁ -C ₃ An alkyl group; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); g ₁ 、G ₂ And G ₃ And G ₁ And G ₃ The two carbon atoms attached together form a heteroaromatic or partially saturated ring system, wherein G ₁ 、G ₂ And G ₃ Selected from nitrogen, sulfur, oxygen and carbon, the bond between two consecutive G's being a single bond, a double bond or an aromatic bond, wherein at least one G represents nitrogen, sulfur or oxygen, and no more than two G's may be oxygen or sulfur, and where two G's are oxygen and/or sulfur they are separated by one carbon atom; from G ₁ 、G ₂ 、G ₃ And the five-membered ring formed by the two carbon atoms to which they are attached is substituted with one to three groups independently selected from X1-Z, with the proviso that X1 is a direct bond, Z is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, (C) ₁ -C ₆ Alkyl) C (=O), (C ₃ -C ₆ Cycloalkyl) C (=o), (C ₁ -C ₆ Alkoxy) C (=o), (C ₃ -C ₆ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkyl sulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, or C ₁ -C ₄ A haloalkylsulfonyl group; or X1 is C ₁ -C ₆ Alkyldiyl, Z is halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, (C) ₁ -C ₆ Alkyl) C (=O), (C ₃ -C ₆ Cycloalkyl) C (=o), (C ₁ -C ₆ Alkoxy) C (=o), (C ₃ -C ₆ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkyl sulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, C ₁ -C ₄ Haloalkyl sulfonyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₆ Cycloalkyl carbonyloxy.

In an embodiment of the first aspect of the invention, the compound of formula Ia has as R ₁ Or C ₁ -C ₃ An alkyl group; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); g ₁ 、G ₂ And G ₃ And G ₁ And G ₃ The two carbon atoms attached together form a heteroaromatic or partially saturated ring system, wherein G ₁ 、G ₂ And G ₃ Selected from nitrogen, sulfur, oxygen and carbon, the bond between two consecutive G's being a single bond, a double bond or an aromatic bond, wherein at least one G represents nitrogen, sulfur or oxygen, and no more than two G's may be oxygen or sulfur, and where two G's are oxygen and/or sulfur they are separated by one carbon atom; from G ₁ 、G ₂ 、G ₃ And the five-membered ring formed by the two carbon atoms to which they are attached is substituted with one to three groups independently selected from X1-Z, with the proviso that X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, or X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy.

In an embodiment of the first aspect of the invention, the compound of formula Ia has as R ₁ Or C ₁ -C ₃ An alkyl group; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); g ₁ 、G ₂ And G ₃ (i) nitrogen, nitrogen and carbon, respectively, or (ii) nitrogen, nitrogen and nitrogen, respectively, or (iii) oxygen, carbon and oxygen, respectively; from G ₁ 、G ₂ 、G ₃ And the five-membered ring formed by the two carbon atoms to which they are attached is substituted with one to three groups independently selected from X1-Z, with the proviso that X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano.

In the first aspect of the inventionIn embodiments, a compound having formula Ib, ic, id, ie, if or Ig has as R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y, wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl; and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, or X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy.

In an embodiment of the first aspect of the invention, the compound of formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y, wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chlorine,Bromine, fluorine, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl; and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano.

In an embodiment of the first aspect of the invention, the compound of formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y, wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6; and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano.

Preferred compounds of formula I in the first aspect are those in table X, table Xa and table P and have the following CAS numbers: 1064904-77-3;1064904-66-0;1064904-87-5;1064900-97-5;1064867-45-3;1064867-33-9;1064862-35-6;1064867-57-7;1064867-09-9;1132938-77-2;1132938-59-0;1132902-80-7;1132892-69-3;1132902-71-6;1132892-60-4;1064889-97-9;1132938-95-4;1064904-98-8;1132902-89-6;1132892-78-4;1132975-68-8;1132975-59-7;1132910-53-2;1132938-19-2;1132926-55-6;1132975-77-9;1132910-72-5;1132910-33-8;1132902-43-2;1132892-42-2;1132926-64-7;1132926-46-5;1132926-28-3;1132986-09-4;1132944-57-0;1132909-83-1;1132986-00-5;1132975-41-7;1132906-69-4;1132895-64-7;1064871-21-1;1132986-18-5;1132978-76-7;1064904-57-9;1132993-87-3;1132993-78-2;1132914-44-3;1132985-82-0;1132930-20-1;1132941-55-9;1132993-96-4;1132904-49-4;1132894-04-2;1132989-09-3;1132977-05-9;1132939-13-9;1132993-52-2;1132902-98-7;1132892-87-5;1132912-88-9;1132975-86-0;1132927-91-3;1064867-21-5;1132996-92-9;1132926-73-8;1132987-47-3;1132910-96-3;1132986-27-6;1132995-34-6;1132938-39-6;1132902-61-4;1132892-51-3;1132994-05-8;1132975-50-8;1132926-37-4;1132910-06-5;1132985-91-1;1132993-69-1;1064909-61-0;1064909-51-8;1064909-71-2;1064905-10-7;1064871-69-7;1064871-57-3;1064862-21-0;1064871-81-3;1132939-84-4;1064871-32-4;1132903-34-4;1132893-23-2;1132939-66-2;1132903-25-3;1132893-14-1;1064889-73-1;1132976-24-9;1064909-82-5;1132940-06-7;1132903-43-5;1132893-32-3;1132927-09-3;1132911-75-1;1132976-15-8;1132927-00-4;1132911-57-9;1132939-30-0;1132927-18-4;1132911-93-3;1132903-07-1;1132892-96-6;1132976-33-0;1132986-63-0;1132926-82-9;1132986-54-9;1132944-73-0;1132911-21-7;1132975-95-1;1132906-78-5;1132895-73-8;1064871-93-7;1064905-13-0;1132994-42-3;1132978-84-7;1132986-72-1;1132994-32-1;1132930-29-0;1132986-36-7;1132914-53-4;1132941-69-5;1132994-51-4;1132904-67-6;1132894-13-3;1132989-18-4;1132977-15-1;1132940-27-2;1132903-52-6;1132893-41-4;1132994-14-9;1132928-00-7;1064871-45-9;1132976-42-1;1132912-97-0;1132997-01-3;1132927-27-5;1132987-56-4;1132912-11-8;1132986-81-2;1132995-43-7;1132939-48-0;1132903-16-2;1132893-05-0;1132994-60-5;1132976-06-7;1132926-91-0;1132911-40-0;1132986-45-8;1132994-23-0;1064910-11-7;1064914-64-2;1064914-74-4;1064909-93-8;1064875-80-4;1064875-93-9;1064862-29-8;1064876-06-7;1132940-83-0;1064875-57-5;1132903-79-7;1132893-68-5;1132941-01-5;1132903-95-7;1132893-77-6;1064889-84-4;1132976-69-2;1064914-86-8;1132941-19-5;1132976-78-3;1132904-13-2;1132893-86-7;1132927-54-8;1132912-52-7;1132927-63-9;1132912-61-8;1132940-48-7;1132927-72-0;1132912-70-9;1132903-61-7;1132893-50-5;1132976-87-4;1132987-11-1;1132927-36-6;1132987-20-2;1132944-85-4;1132912-29-8;1132976-51-2;1132906-87-6;1132895-87-4;1064876-17-0;1064909-99-4;1132994-87-6;1132978-93-8;1132987-29-1;1132994-96-7;1132930-38-1;1132986-93-6;1132914-63-6;1132941-87-7;1132995-05-1;1132904-85-8;1132894-22-4;1132989-27-5;1132977-27-5;1132941-37-7;1132904-31-4;1132893-95-8;1132994-69-4;1132928-09-6;1064875-66-6;1132976-96-5;1132913-06-4;1132997-10-4;1132927-82-2;1132987-65-5;1132912-79-8;1132987-38-2;1132995-52-8;1132940-66-9;1132903-70-8;1132893-59-4;1132995-14-2;1132976-60-3;1132927-45-7;1132912-43-6;1132987-02-0;1132994-78-5;1132946-04-3;1132907-58-4;1132896-32-2;1132945-95-9;1132907-49-3;1132896-14-0;1132946-13-4;1132907-67-5;1132896-51-5;1132915-19-5;1132980-76-7;1132915-10-6;1132915-28-6;1132980-67-6;1132945-77-7;1132907-31-3;1132895-78-3;1132980-85-8;1132931-95-3;1132932-04-7;1132931-86-2;1132914-92-1;1132931-68-0;1132989-89-9;1132949-28-0;1132911-51-3;1132901-13-3;1132989-80-0;1132980-49-4;1132989-98-0;1132984-78-1;1132918-18-3;1133000-29-9;1133000-19-7;1132989-62-8;1133000-41-5;1132947-39-7;1132935-12-6;1132908-96-3;1132898-81-7;1132993-14-6;1132999-73-5;1132982-36-5;1132946-22-5;1132916-55-2;1132907-76-6;1132896-67-3;1133006-76-4;1132933-31-3;1132980-94-9;1132915-37-7;1132991-48-0;1132932-13-8;1132990-07-8;1133003-24-3;1132945-86-8;1132907-40-4;1132895-96-5;1133000-55-1;1132980-58-5;1132931-77-1;1132915-01-5;1132989-71-9;1132999-98-4;1132946-58-7;1132908-14-5;1132897-40-5;1132946-49-6;1132908-04-3;1132897-22-3;1132915-73-1;1132981-29-3;1132946-67-8;1132908-24-7;1132897-58-5;1132915-64-0;1132932-49-0;1132981-20-4;1132915-82-2;1132932-40-1;1132946-31-6;1132907-86-8;1132896-85-5;1132932-59-2;1132981-38-4;1132990-47-6;1132932-22-9;1132915-46-8;1132990-38-5;1132949-39-3;1132911-68-2;1132901-30-4;1132981-03-3;1133001-17-8;1132990-56-7;1132984-95-2;1133001-01-0;1132918-26-3;1132990-16-9;1132935-20-6;1133001-35-0;1132947-48-8;1132909-05-7;1132898-90-8;1132993-24-8;1132982-45-6;1132946-76-9;1133000-69-7;1132908-33-8;1132897-76-7;1132916-64-3;1132933-40-4;1133006-96-8;1132981-48-6;1132932-68-3;1132915-91-3;1132991-59-3;1132990-65-8;1133003-53-8;1132946-40-7;1132907-95-9;1132897-03-0;1133001-60-1;1132981-11-3;1132932-31-0;1132915-55-9;1132990-29-4;1133000-84-6;1132947-03-5;1132908-60-1;1132898-30-6;1132947-12-6;1132908-69-0;1132898-48-6;1132916-18-7;1132981-93-1;1132947-21-7;1132908-78-1;1132898-63-5;1132916-27-8;1132982-09-2;1132932-95-6;1132933-04-0;1132916-36-9;1132946-85-0;1132908-42-9;1132897-94-9;1132933-13-1;1132982-18-3;1132991-00-4;1132932-77-4;1132916-00-7;1132991-09-3;1132949-52-0;1132911-86-4;1132901-48-4;1132981-59-9;1133002-29-5;1132991-27-5;1133002-47-7;1132985-13-7;1132918-35-4;1132990-74-9;1132935-29-5;1133002-69-3;1132947-57-9;1132909-14-8;1132898-99-7;1132993-33-9;1132982-54-7;1132947-30-8;1133001-86-1;1132908-87-2;1132898-72-6;1132916-73-4;1132933-49-3;1133007-15-4;1132982-27-4;1132933-22-2;1132916-45-0;1132991-68-4;1132991-36-6;1133003-80-1;1132946-94-1;1132908-51-0;1132898-12-4;1133002-96-6;1132981-75-9;1132932-86-5;1132916-09-6;1132990-90-9;1133002-09-1;1114234-66-0;1114230-63-5;1114230-52-2;1114230-44-2;1114230-36-2;1114230-25-9;1114230-16-8;1114229-82-1;1114225-78-3;1114225-71-6;1114225-60-3;1114225-51-2;1114225-40-9;1114225-33-0;1114226-16-2;1114226-07-1;1114226-23-1;1114229-62-7;1114225-89-6;1114231-02-5;1114230-94-2;1114226-32-2;1114231-10-5;1114234-48-8;1114230-75-9;1114231-21-8;1114225-98-7;1114230-83-9;1114226-65-1;1114226-76-4;1114226-87-7;1114229-71-8;1114226-43-5;1114231-54-7;1114231-63-8;1114226-98-0;1114231-74-1;1114234-57-9;1114231-32-1;1114231-85-4;1114226-54-8;1114231-43-4;1064960-93-5;1064960-87-7;1064960-98-0;1064933-81-8;1064933-76-1;1064934-72-0;1064960-77-5;1064938-31-3;1064938-25-5;1064938-34-6;1064933-64-7;1064944-59-7;1064938-13-1;1064937-94-5;1064974-25-9;1064961-03-0;1064934-80-0;1064938-42-6;1064960-82-2;1064933-70-5;1064938-19-7;1064960-01-5;1064959-95-0;1064935-01-8;1064938-65-3;1064973-77-8;1064934-97-9;1064938-61-9;1064959-83-6;1064935-10-9;1064938-71-1;1064934-85-5;1064944-47-3;1064938-48-2;1064937-81-0;1064978-19-3;1064960-14-0;1064935-14-3;1064938-78-8;1064959-89-2;1064934-91-3;1064938-53-9;1064955-75-4;1064955-80-1;1064955-85-6;1064935-31-4;1064976-24-4;1064935-35-8;1064955-65-2;1064971-76-1;1064935-41-6;1064944-53-1;1064971-82-9;1064930-87-5;1064938-83-5;1064937-88-7;1064965-07-6;1064955-93-6;1064935-47-2;1064971-88-5;1064955-70-9;1064935-25-6; and 1064938-89-1 (hereinafter referred to as list Q).

Certain compounds of list Q are disclosed in WO 2009024341, WO 2007093402 and WO 2009010260.

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Halogen or C of (2) ₁ -C ₃ An alkyl group; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); and X1 is a direct bondAnd Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, or X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy, provided that (i) when R ₃ R in the case of 3-chloro-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Halogen or C of (2) ₁ -C ₃ An alkyl group; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, or X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy, provided that (i) when R ₃ R in the case of monohalo-pyridin-2-yl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is monohalo-pyridin-2-yl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, or X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy, provided that (i) when R ₃ R in the case of 3-chloro-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, C ₃ -C ₄ Halogenated cycloalkyl, (C) ₁ -C ₃ Alkyl) C (=O), (C ₃ -C ₃ Cycloalkyl) C (=o), (C ₁ -C ₃ Alkoxy) C (=o), (C ₃ -C ₄ Cycloalkoxy) C (=o), benzyl, halogenSubstituted benzyl, C ₁ -C ₃ Alkyl sulfanyl, C ₁ -C ₃ Alkylsulfinyl, C ₁ -C ₃ Alkylsulfonyl, C ₁ -C ₃ Haloalkyl sulfanyl, C ₁ -C ₃ Haloalkyl sulfinyl, or C ₁ -C ₃ Haloalkylsulfonyl, or X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₄ Cycloalkyl carbonyloxy, provided that (i) when R ₃ R in the case of monohalo-pyridin-2-yl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is monohalo-pyridin-2-yl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano, provided that (i) when R ₃ R in the case of 3-chloro-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya to Yj, and R ₇ Is chloro, bromo, fluoro, difluoromethyl, trifluoromethyl, cyclopropyl or phenyl substituted by trifluoromethyl); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano, provided that (i) when R ₃ R in the case of monohalo-pyridin-2-yl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is monohalo-pyridin-2-yl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl、C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano, provided that (i) when R ₃ R in the case of 3-chloro-2-pyridinyl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Halogen, C of (2) ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or X2-Y (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano, provided that (i) when R ₃ R in the case of monohalo-pyridin-2-yl ₄ Not CF ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is monohalo-pyridin-2-yl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ Trifluoromethyl, bromine, chlorine,Methoxy or X2-Y (wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano, provided that (i) when R ₃ R in the case of monohalo-pyridin-2-yl ₄ Not OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is monohalo-pyridin-2-yl and X1-Z is different from hydrogen, R ₄ Not OCHF ₂ 。

In embodiments of each aspect of the invention, the compound having formula Ib, ic, id, ie, if or Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ X2-Y of (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9); and X1 is a direct bond and Z is hydrogen, halogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano.

In an embodiment of each aspect of the invention, the compound of formula Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ X2-Y of (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya 17), methoxy or OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the And X1 is a direct bond and Z is halogen.

In an embodiment of each aspect of the invention, the compound of formula Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as a means ofR ₄ X2-Y of (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9), methoxy or OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the And X1 is a direct bond and Z is halogen.

In an embodiment of each aspect of the invention, the compound of formula Ig has the formula R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ X2-Y of (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9), methoxy or OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the And X1 is a direct bond and Z is fluoro-)

In an embodiment of each aspect of the invention, the compound having formula Ib has as R ₁ Methyl, chlorine or bromine; as R ₃ 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; as R ₄ X2-Y of (wherein X2 is CH) ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9), trifluoromethyl, methoxy or OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the And X1 is a direct bond and Z is fluoro-)

In a third aspect, the present invention makes available a composition comprising a compound having formula I as defined in the second aspect, one or more adjuvants and diluents, and optionally one or more other active ingredients.

In a fourth aspect, the present invention makes available a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound as defined in the second aspect or a composition as defined in the third aspect.

In a fifth aspect, the present invention makes available a method for protecting plant propagation material from attack by insects, acarines, nematodes or molluscs, which comprises treating the propagation material or the locus in which the propagation material is planted with an effective amount of a compound of formula I as defined in the second aspect or a composition as defined in the third aspect.

In a sixth aspect, the present invention makes available a plant propagation material, such as a seed, comprising a compound of formula I as defined in the second aspect or a composition as defined in the third aspect, or treated with the compound or the composition, or having the compound or the composition attached thereto.

The compounds of formula I may be prepared by methods known to those skilled in the art. More specifically, compounds and intermediates having formula I can thus be prepared as described in schemes and examples below. For clarity, certain stereocenters are not indicated and are not intended to limit the teachings of these schemes in any way.

The process according to the invention for preparing the compounds of formula I is carried out by methods known to the person skilled in the art. In particular, WO 2007/093402 or WO 2009/024441 describes a process for preparing certain bicyclic diamide compounds.

The compounds of formula I (when A is S) can be prepared from compounds of formula Ia, for example, as depicted in scheme 1, by reaction with a sulfiding agent such as, for example, lawson' S reagent or phosphorus sulfide (P) ₂ S ₅ ) Treatment to prepare. The vulcanization of amides is well known and many examples are found in the literature. If the regioselectivity of the sulphide is insufficient, the compounds of formula I may have to be separated from the regioisomers.

Reaction scheme 1: preparation of a compound having formula I:

compounds of formula Ia (wherein R ₁ 、G ₁ 、G ₂ 、G ₃ 、X ₁ 、Z、R ₃ And R ₄ As defined in formula Ia) can be obtained from a benzoxazinone compound having formula II as depicted in reaction scheme 2 by treatment with ammonia or an equivalent of ammonia such as, for example, ammonium acetate or ammonium hydroxide. Various solvents may be used, such as, for example, ethers, such as tetrahydrofuran, or polar aprotic solvents, such as acetonitrile, or alcohols, such as methanol or ethanol, or aqueous solutions or combinations thereof. Reverse-rotationIt should be possible to carry out advantageously with an excess of ammonia or equivalent at elevated temperature or pressure, generally between 20 ℃ and 80 ℃.

Reaction scheme 2: ammonolysis of a compound having formula II:

compounds of formula II (wherein R ₁ 、G ₁ 、G ₂ 、G ₃ 、X ₁ 、Z、R ₃ And R ₄ As defined in formula Ia) are particularly useful for preparing compounds having formula Ia. They are key intermediates for the preparation of compounds of formula I and are also part of the present invention.

Benzoxazinones of formula II (wherein R ₁ 、G ₁ 、G ₂ 、G ₃ 、X ₁ 、Z、R ₃ And R ₄ As defined in formula Ia) may be prepared by reacting an anthranilic acid-type compound having formula III (wherein R ₁ 、G ₁ 、G ₂ 、G ₃ 、X ₁ And Z is as defined in formula I) with a pyrazolecarboxylic acid compound of formula IV (wherein R ₃ And R ₄ As defined in formula I) by using dehydration conditions such as the reaction depicted in reaction scheme 3

Reaction scheme 3: preparation of benzoxazinones having formula II:

similar reactions have been described in the literature and can be carried out by first activating the pyrazolecarboxylic acid (e.g. as an acid halide or anhydride) and then coupling it with anthranilic acid under further dehydration conditions. A common method of carrying out this conversion is to combine the compound of formula III and the compound of formula IV in one step in the presence of, for example, an acid chloride such as an alkyl-or arylsulfonyl chloride (preferably but not limited to methanesulfonyl chloride). Many similar examples of this type of transformation are described in the literature, as for example in WO 2007093402, WO 2009010260, WO 2009024341, WO 2014128136.

Many bis-anthranilic acids are described in the literature, and compounds having formula III can be prepared by those skilled in the art as already described or in a similar manner.

Likewise, a number of pyrazolecarboxylic acids are described in the literature, and compounds of the formula IV can be prepared as already described or in a similar manner by a person skilled in the art (for example in WO 04/067528, WO 10069502, WO 2011/157664, WO 04046129). Some of which are also commercially available.

Reaction scheme 3a: alternative preparation of compounds having formula I (wherein a is sulfur):

an alternative method for obtaining a compound having formula I (wherein a is sulfur) is depicted in reaction scheme 3 a.

Anthranilic acid having formula III can be converted to anthranilic acid amides having formula IIIa. Many conditions for such transformation are described in the literature. For example, anthranilic acid may be treated with carbonyldiimidazole or with 1-hydroxybenzotriazole and 1-ethyl-3- (3' -dimethylaminopropyl) carbodiimide hydrochloride in a polar aprotic solvent such as dimethylformamide, followed by treatment with ammonia (as described in Nathubhai Amit et al, J. Med. Chem. [ J. Pharmaceutical J ] (2017), 60 (2), 814-820).

In the following step, the compound having formula IIIa may be treated with a sulfiding agent to produce a thioamide having formula IIIb. Examples of sulfiding agents are Lawson's reagent or phosphorus sulfide (P ₄ S ₁₀ ). The reaction may be carried out in toluene or an ether solvent, typically at elevated temperature.

Finally, treatment of the compound of formula IIIb with a carboxylic acid of formula IV can be converted to a compound of formula I wherein A is sulfur. In order to carry out the amidation reaction, the acid must be activated. Examples of activation are conversion to an acid halide (e.g. an acid chloride), or to an anhydride or mixed anhydride, or by using a coupling agent. The formation of amide bonds from amines and carboxylic acids is a very common reaction in organic chemistry.

A compound having formula IVb (wherein R ₃ Having the meaning given for formula I and Y0 being Y as defined for formula I) is generally known or can be prepared by a person skilled in the art. A typical example of such a synthesis is shown in reaction scheme 3 b.

Reaction scheme 3b

For example, a compound of formula IVb can be prepared by reacting a compound of formula V (wherein Y0 is as defined above and M is an alkali metal such as lithium, sodium, potassium) with a compound of formula IVa (wherein R ₃ Having the meaning given for formula I and X0 is chlorine, bromine or iodine) in a suitable solvent which may comprise, for example, acetone or tetrahydrofuran, optionally in the presence of potassium iodide as catalyst.

A compound having formula IVa (wherein R ₃ Having the meaning given for formula I and X0 is chlorine, bromine or iodine) can be prepared from compounds of the formula VI (wherein R ₃ Having the meaning given for formula I, R ₉ Is C ₁ -C ₃ Alkyl and X0 is chloro, bromo or iodo) in a suitable solvent such as tetrahydrofuran, methanol or dioxane under basic conditions which may include, for example, lithium hydroxide or sodium hydroxide. Such methods have been described previously in, for example, WO 2011073101. The compounds of formula VI are generally known or can be readily prepared by one skilled in the art. A typical example of such a synthesis is described in WO 2011073101.

When one or more groups G in the compound of formula Ia are nitrogen, the compound of formula X on the nitrogen atom ₁ The group of-Z may be present already in the stage of the intermediate anthranilic acid of formula III, but may also be introduced in a subsequent stage, as described in scheme 4. When defined above, the group G is N-X ₁ -Z andthis is particularly valuable when the subsequent chemical reaction conditions are too unstable.

Reaction scheme 4: substitution at the ring nitrogen atom in a subsequent stage

For subsequent functionalization of the heterocyclic nitrogen atom, the unsubstituted bicyclic core of the compounds of formulae Ib and Ic (tautomeric forms) and formulae Id, ie and If (also tautomeric forms) may be used with a compound of formula Z-X ₁ Compound treatment of LG wherein X ₁ -Z is as defined in the compound of formula I and LG is a leaving group, for example a halide, preferably chloro, bromo or iodo, acyloxy or alkyl-or arylsulfonyloxy, preferably tosyloxy or mesyloxy. Of course, other leaving groups may be used depending on the ease of access and the reactivity. Preferably, the reaction is carried out in an inert solvent and in the presence of a base such as, but not limited to, a huning base or pyridine or a metal alkoxide such as t-BuOK or a metal carbonate such as Cs ₂ CO ₃ Or a metal hydride such as NaH. Depending on the compound involved, the reaction can also be carried out in the absence of a base. The reaction may produce one or more regioisomers that may be separated. In some cases, conditions may be found in which one of the product regioisomers predominates.

Depending on the procedure or reaction conditions, the reactants may 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, alkylenediamines, free or N-alkylated saturated or unsaturated cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Examples which may be mentioned are sodium hydroxide, sodium hydride, sodium amide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis (trimethylsilyl) amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-cyclohexyl-N, N-dimethylamine, N-diethylaniline, pyridine, 4- (N, N-dimethylamino) pyridine, quinuclidine, N-methylmorpholine, benzyltrimethylammonium hydroxide and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU).

These reactants may be reacted with each other as they are, i.e., without the addition of solvents or diluents. However, in most cases it is advantageous to add inert solvents or diluents or mixtures of these. If the reaction is carried out in the presence of a base, the base employed in excess (e.g., triethylamine, pyridine, N-methylmorpholine or N, N-diethylaniline) may also act as a solvent or diluent.

These reactions are advantageously carried out at temperatures ranging from about-80 ℃ to about +140 ℃, preferably from about-30 ℃ to about +100 ℃, in many cases between ambient temperature and about +80 ℃.

Depending on the reaction conditions and the choice of starting materials which are suitable for the respective case, it is possible, for example, to replace only one substituent with another substituent according to the invention in one reaction step, or to replace a plurality of substituents with other substituents according to the invention in the same reaction step.

Salts of the compounds of formula I may be prepared in a manner known per se. Thus, for example, the acid addition salts of the compounds of formula I are obtained by treatment with a suitable acid or a suitable ion exchanger reagent, and the salts with bases are obtained by treatment with a suitable base or with a suitable ion exchanger reagent.

Salts of the compounds of formula I may be converted in a conventional manner into the free compounds I, acid addition salts (e.g. by treatment with suitable basic compounds or with suitable ion exchanger reagents) and salts with bases (e.g. by treatment with suitable acids or with suitable ion exchanger reagents).

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

These compounds of formula I having salifying properties may be obtained in free form or in salt form, depending on the procedure or reaction conditions.

Depending on the number, absolute and relative configuration of the asymmetric carbon atoms present in the molecule and/or on the configuration of the non-aromatic double bonds present in the molecule, the compounds of the formula I and, where appropriate, the tautomers thereof (in each case in free form or in salt form) may be present in the form of one of the possible isomers or as a mixture of these, for example in the form of pure isomers, such as enantiomers and/or diastereomers, or as an isomeric mixture, such as an enantiomeric mixture, for example a racemate, a diastereomeric mixture or a racemic mixture; the present invention relates to the pure isomers and also to all possible isomer mixtures and should be understood as such in each case above and below even if stereochemical details are not explicitly mentioned in each case.

Diastereomeric mixtures or racemate mixtures of compounds of the formula I in free form or in salt form, which may be obtained depending on the starting materials and procedures chosen, can be separated into the pure diastereomers or racemates in a known manner on the basis of the physicochemical differences of these components, for example by fractional crystallization, distillation and/or chromatography.

Mixtures of enantiomers (e.g., racemates) that can be obtained in a similar manner can be resolved into the optical enantiomers by known methods, for example by recrystallization from optically active solvents; by chromatography on chiral adsorbents, for example High Performance Liquid Chromatography (HPLC) on acetyl cellulose; by cleavage with a specific immobilized enzyme by means of a suitable microorganism; by forming an enveloping compound, for example using a chiral crown ether, wherein only one enantiomer is complexed; or by conversion to a salt of a diastereomer, for example by reaction of the basic end product racemate with an optically active acid, such as a carboxylic acid, for example camphoric acid, tartaric acid or malic acid, or a sulfonic acid, for example camphorsulfonic acid, and separation of the diastereomeric mixture which can be obtained in this way, for example by fractional crystallization on the basis of their different solubilities, to give the diastereomer from which the desired enantiomer can be brought to the free form by the action of a suitable reagent, for example an alkaline reagent.

Pure diastereomers or enantiomers can be obtained according to the invention not only by separation of suitable isomer mixtures but also by generally known methods of diastereoselective or enantioselective synthesis, for example by carrying out the method according to the invention with starting materials having suitable stereochemistry.

By reacting a compound of formula I with a suitable oxidizing agent (e.g., H ₂ O ₂ Urea adducts) are reacted in the presence of an anhydride (e.g., trifluoroacetic anhydride) to produce an N-oxide. Such oxidation is described in the literature, for example, in J.Med.chem. [ J.pharmaceutical chemistry]Known from 32 (12), 2561-73,1989 or WO 2000/15615.

If the individual components have different biological activities, it is advantageous to separate or synthesize in each case the biologically more effective isomers, for example enantiomers or diastereomers or isomer mixtures, for example enantiomer mixtures or diastereomer mixtures.

If appropriate, the compounds of the formula I and, where appropriate, the tautomers thereof (in each case in free form or in salt form) can also be obtained in the form of hydrates and/or include other solvents, for example those which can be used for crystallizing compounds which are present in solid form.

The compounds of formula I represented in table X and table Xa can be prepared according to the methods described above. The following examples are intended to illustrate the invention and illustrate preferred compounds of formula I.

Table X: compounds of formula I

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_Xa Table Xa: compounds of formula I represented by formula I

Wherein the method comprises the steps of

The compounds of formula I according to the invention are active ingredients of prophylactic and/or therapeutic value in the field of pest control, have a very favourable biocidal spectrum and are well tolerated by warm-blooded species, fish and plants, even at low application rates. These active ingredients according to the invention act on all or individual developmental stages of normally sensitive and also resistant animal pests, such as insects or representatives of the order acarina. The insecticidal or acaricidal activity of the active ingredient according to the invention can manifest itself directly, i.e. the destruction of the pest occurs immediately or only after some time has elapsed (for example during molting); or indirectly, e.g., reducing spawning and/or hatching rate.

Examples of animal pests mentioned above are:

from the order Acarina (Acarina), for example,

the species of the genus goiter (Acalitus spp), the species of the genus goiter (Aculus spp), the species of the genus goiter (Aculilus spp), the species of the genus Oncomelania (Aceria spp), the species of the genus Talaromyces (Acarus siro), the species of the genus Blumeria (Amblyomma spp.), the species of the genus Alternaria (Argus spp.), the species of the genus Bopyrilus (Boohilus spp.) Brevipira species (Brevipalpus spp.), porphyra species (Bryoba spp.), celopharum species (Calipilimus spp.), dermatophagoides species (Choriopes spp.), dermatophagoides pteronyssinus (Dermanyssus gallinae), epidermomyces species (Dermatophagoides spp), tetranychus species (Eotetranychus spp), celopyrus species (Eriopneus spp.), cycloparatus species (Eriophtalmus spp.), the species of the genus Tarsonius (Hemitarsonemus spp), the species of the genus Hyalomma (Hyalomma spp.), the species of the genus hard tick (Ixodes spp.), the species of the genus Rhagoraphis (Olygonchatus spp.), the species of the genus Blumeria (Ornithiodoros spp.), the species of the genus Tarsonius (Polyphagotarsone latus), the species of the genus Pannychus (Pannychus spp.), the species of the species Rhapontici (Phyllocoptruta oleivora), the species of the species Phytophagus (Phytoxus spp), the species of the genus Tarsonii (Polyphagotarsonemus spp), the species of the genus Porphyra (Psoropsis spp), the species of the species Rhipicephalus (Rhipicephalus spp.), the species of the species Rhizoctophagus spp), the species of the genus Rhizoctopus spp, the species of the genus Sarcops (Sarcops spp), the species of the genus Tarsonius (Steneotarsonemus spp), tarsonemus species (Tarsonemus spp.);

From the order of the lice (anoplus), for example,

the species of the genus sanguinea (haematoplus spp.), the species of the genus ulna (lingnathus spp.), the species of the genus Pediculus (Pediculus spp.), the species of the genus gomphrena (pepphigus spp.), and the species of the genus rhizobium (Phylloxera spp.);

from Coleoptera (Coleoptera), for example,

the species of kowtow (agriosphaera spp.), delphinidia (Amphimallon majale), eastern ali tortoise (Anomala orientalis), hupezium species (Anthonomus spp.), hupezium species (Aphodius spp), corn pseudoflower (Astylus atromaculatus), chafer species (Ataenius spp), beet cryptotaenia (Atomaria linearis), beet tibiala (Chaetocnema tibialis), lucida species (Cerotoma spp), amethyst species (Conoderus spp), root neck species (Cosmopolites spp.), green flower tortoise (cotinida), curvularia species (Curvulio spp.), rhinocerotis species (Cyclocopa spp), dermestes spp the species of the genus rhododendron (Diabrotica spp), argentina (Diloboderus abderus), ladybug species (Epilochna spp), coleoptera (Eremus) species, hemioga (Heteronychus arator), coffee bean beetle (Hypothenemus hampei), lagria virusta (Lagria vilosa), solanum tuberosum (Leptinotarsa decemlineata), oryza species (Liogenys) species, megasporapus (Maecaaspis) species, williams (Maladera castanea), comama species (Megasgis spp), saponaria species (Melighetes aeneus), himalayana species (Melongena spp), mecanella parviflora (Myochrous armatus), orychalimax species (Orychips spp), the species of the genus euonymus (Otiorhynchus spp.), the species of the genus Tortomium (Phyllophaga spp.), the species of the genus Popilia (Phyllophaga spp.), the species of the genus Tortomium (Popilia spp.), the species of the genus Poplides (Psylliosp.), the species of Rasche Ma Tusi Oibuja (Rhyssomatus aubtilis), the species of the species Rhizopus hijacking (Rhizopertha spp.), the family scarabaeidae (Scarabidae), the species of the genus Michelia (Sitophilus spp.), the species of the genus Fatoga (Sitotrop spp.), the species of the genus pseudoradices (Somaticus spp.), the species of the species Cryptocaryophyllus, the species of the species Glycine (Sternechus subsignatus), the species of the species Poneium (Tenebrio spp), the species of the species Rhizoctopus sp);

From Diptera (Diptera), for example,

aedes species (Aedes spp.), anopheles species (Anopheles spp), chinese sorghum mosquito (Antherigona soccata), olive fruit fly (Bactrocea oleae), garden Mao Wen (bieo hortollanus), bradysia species (Bradysia spp), red head fly (Calliphora erythrocephala), bactrocera species (Ceratitis spp.), chrysomyia species (Chrysomyia spp.), culex species (Culex spp.), huang Ying species (Cuterebra spp.), oligochaeta spp.), geotrichia species (Deltaa spp), black abdomen fruit fly (Drosophila melanogaster), toilet species (Fannia spp.), gastric fly species (Gastrohilus spp), ji Mi Zasan (Geomyza tripunctata), glossa species (Glospp); the species of dermatophagoides (Hypoderma spp.), the species of lupulus (hyppoboca spp.), the species of Liriomyza (Liriomyza spp.), the species of green fly (Lucilia spp.), the species of black fly (Melanagromyza spp.), the species of family fly (Musca spp.), the species of crazy fly (Oestrus spp.), the species of gomphora (Orseolia spp.), the species of swedish straw fly (oscilliella frat), the species of chenopodium (Pegomyia hyoscyami), the species of tspecia spp (phonbia spp.), the species of round fruit fly (rhagomphsis spp), the species of Ravela tetra vaccum (Rivelia quadrifasciata), the species of Scatagla (Scatella), the species of Musca (Sciara spp.), the species of stina sting fly (Stomomyza spp.) Tabanus species (Tabanus spp.), taenia species (Tannia spp.), and Davida species (Tipula spp.);

From the order Hemiptera (Hemiptera), for example,

oncorhynchus (Acanthocoris scabrator), apostigma species (Acrosternum spp), apostigma lucorum (Adelphocoris lineolatus), aleurodes species, apostigma turcicum (Amblypelta nitida), apostigma glabra (Bathycoelia thalassina), apostigma species, ainsus species, pogostemon cablin (Clavigralla tomentosicollis), apostigma species (Cronemades spp), theobroma cacao, apostigma species, lepidus species, edssa species (Edessa spp), aleurodes species (Eucheulus spp), hexabanus (Eurydema pulchrum), aleurus species, theobroma sinensis, aleurus maculatus (Horcias nobilellus) the species of the genus stinkbug, lygus species, tropical major species, cabbage plant bug (Murgantia histrionic), neo-lygus species, lygus (Nesidiocoris tenuis), green plant bug species, lygus (Nysius simulis), sea-island plant bug, lygus species, red plant bug species, cocoa plant bug, chestnut plant bug (Scaptocoris castanea), black plant bug species (scotinopyhara spp.), thebaita (thyantta) species, trypanosoma species, tapioca (vactillus);

Aldazus (Acyrthosium pisum), aldage (Adalges) species, algancicla (Agalliana ensigera), talargevein psylla, aleurodicus species (Aleurodicus spp.), aleuroculus species (Aleuroculus spp.), saccharum officinarum, aleurodera (Aleurothrixus floccosus), aleurodera (Aleyrodes brassicae), otophus gossypii (Amarasca biguttula), aleurodera (Citrus aurantifolia), pianotus species, aleurodera species, aphis aphidae, aphis species, aleurodera species (Aspirpus spp.), aleurodera solanacea, solanum/Lycopersicum (Bactericera cockerelli), aleurodicus species (Brachypymadus spp), brassica oleracea, aphis, pieri (Cavariella aegopodii Scutella), lepidium species, philis, philippica, aleuropaea the species of Emblica, emblica (Cofana spp), cryptotaenia, emblica, phanerochaete, zea mays Huang Chi, bemisia, citrus psyllium, mylabris, cephalotaxus, emblica, gastrodia, eucalyptus (Glycaspis brimblecombei), sinonotus, aphis (Hyadaphis pseudobrassicae), hyalocephalus (Hyalterus spp), ulmus (Hyperomyzus pallidus), emblica (Idioscopus clypealis), africa, latifolia, gecko, pleuropus, lopa aphis, lagerstroemia, lygenei, okaki, okava, hypsida, hypsizygus, the plant species may be selected from the group consisting of Cerrididae (Metcalfa pruinosa), mylabris, oenomyzus, neotoxoptera sp, nilaparvata lugens (Nilapia spp.), nilaparvata lugens, aldorus Ji Lasi (Odonaus rutha), saccharum sinensis, aleurites graminis, phyllostachys kaki, ericerus, zea maydis, alternaria, bullera, rhapontica, phylloxera spp, pediococcus, sang Baidun, lecania, leucocerus, and Leucocerus gossypii (Pseudatomoscelis seriatus) the plant species may be selected from the group consisting of Phyllostachys species, ericerus (Pulvinaria aethiopica), leptoradix species, quesada gigas (Quesada gigas), electro-optic leafhoppers (Recilia dorsalais), sinonotus species, hemizus species, eyema species, aphis species, myzus species (Sitobion spp.): white flea, trickpis (Spissistilus festinus), brown planthopper (Tarophagus Proserpina), aphis species, aleyrodid species, tricks taboli (Tridiscus sporoboli), mealybugs species (Trionymus spp), african psylli, cerclage, leafhoppers, sagradares (Zyginidia scutellaris);

From Hymenoptera (Hymenoptera), for example,

the genus acrophyllomyrmex (Acromyrmex), trichium species (range spp.), phyllomyrmen species (Atta spp.), phyllomyrtus species (Cephus spp.), melissa species (Diprionidus spp.), apriona (Gilpinia polytoma), apriona species (Hoplocalyxpa spp.), mao Yi species (Lasius spp.), yellow ant (Monomorium pharaonis), neophyllomyrtus species (neodopteran spp.), agricultural species (Pogonomomyrmem spp), red fire ants, water ant species (Solenopsis spp.), and wasp species (Vespa spp.);

from the order isoptera, for example,

coptermes spp, termites Corniternes cumulans, jacaragonis spp, macrotermes spp, australis spp, microctermes spp, rottermes spp, reticletes spp; fire ant tropical (Solenopsis geminate)

From the order Lepidoptera (Lepidoptera), for example,

the species of Philips, spodoptera, cotton leaf worm, amylois, spodoptera, yellow leaf roller, agrocybe (Argyresthia spp), philips, spodoptera, cotton leaf roller, corn earworm, pink moth, peach moth, gramineae, chrysosporium, etc cranberry grass moth (Chrysoteuchia topiaria), grape fruit moth, leaf roller, sphaerella, hedgehog (Colias lesbia), red bean powder butterfly (Colias lesbia) Spodoptera frugiperda (Cosmoshila flava), orthosiphon aristatus, plutella xylostella, apocynum venetum, buxarus chinensis, plutella species, buxarus chinensis, leptoradix Tripterygii Wilfordii species, and Leptoradix Tripterygii Wilfordii species the plant species selected from the group consisting of cotton bollworms, spodoptera sp, southern corn leaf rollers (Elasmopalpus lignosellus), sweet potato stem rollers, pink leaf rollers, leaf rollers (epiothia spp), salt eupatorium acrea (Estigmene acrea), bean pod rollers (Etiella zinckinella), plutella sp, ring needle roller, huang Due, cut root worm, fei Di jacket particle non (Feltia jaculiferia), small borer sp (Grapholita spp.), white-wing plutella xylostella, spodoptera sp, cabbage caterpillar, cut She Yeming sp (Herpetogramma spp), fall webworm, tomato moth, la Ma Pali Sirocco (Lasmopalpus lignosellus), leaf rollers, grape leaf rollers, luo Sidi ratio (Loxostege bifidalis), diamond back moth sp, sphaera sp, curtain moth sp, cabbage looper, tobacco looper, spodoptera species (Mythimna spp), spodoptera species, fall armyworm species, ornithogali (Ornites indica), european corn borer, ultra-small leaf roller species, and tobacco leaf roller Phaeodactyla species, spodoptera exigua, hedyotis, and Leptopetalum one-star armyworm, potato moths, cabbage butterflies, pink butterflies, plutella xylostella, and the like Cellula species, leptopetalum species, mentha spicata (Rachiplus nu), geotrichum sibiricum (Richia albicosta), bai He Orthosiphon species (Scirpophaga spp.), spodoptera species, spodoptera frugiperda, cynoma, and Cynoma the species of the genus Leptopetalum, the species of the genus Leptopetalum the species of the genus heteronavirus, the species of the genus strongylonia, the species of the genus spodoptera;

From the order of the pileata (Mallophaga), for example,

beasts species (Damalinea spp.) and trichomadillidium species (trichomadactes spp.);

from the order Orthoptera (Orthoptera), for example,

a Periplaneta species (Blatta spp.), a Periplaneta species (blattalla spp.), a mole cricket species (grylotalpa spp.), a madagago (Leucophaea maderae), a migratory locust species (Locusta spp.), north cricket (Neocurtilla hexadactyla), a Periplaneta species (Periplaneta spp.), a nevus cricket species (Scapteriscus spp), and a desert locust species (Schistocerca spp.);

from the order of the rodentia (pseudoaltera), for example,

a species of the genus bezoa (Liposcelis spp.);

from the order of the fleas (Siphonaptera), for example,

a flea species (Ceratophyllus spp.), a Ctenocephalides spp, a queen flea (Xenopsylla cheopis);

from the order Thysanoptera (Thysanoptera), for example,

ke Lichu Phillips (Calliothrips phaseoli), frankliniella species (Frankiniella spp.), mallotus species (Helithps spp), philippia species (Hercothrips spp.), monophila species (Parthenothrips spp), scirpus africanus (Scirtothrips aurantii), soy Thrips (Sericothrips variabilis), pethrips species (Taeniothrips spp.), thrips species (Thips spp);

From the order of the Thysanora, for example, tuna (Lepisma saccharina).

In another aspect, the invention may also relate to a method of controlling damage to plants and parts thereof by plant parasitic nematodes (endoparasitic-, semi-endoparasitic-, and ectoparasitic nematodes), in particular plant parasitic nematodes such as root-knot nematodes (root knot nematodes), northern root-knot nematodes (Meloidogyne hapla), southern root-knot nematodes (Meloidogyne incognita), javaroot-knot nematodes (Meloidogyne javanica), arachnids (Meloidogyne arenaria), and other root-knot nematode species; cyst forming nematodes (cyst-forming nematodes), golden-potato nematodes (Globodera rostochiensis), and other species of the genus saccharis (Globodera); cereal cyst nematodes (Heterodera avenae), soybean cyst nematodes (Heterodera glycines), beet cyst nematodes (Heterodera schachtii), heterodera rubra (Heterodera trifolii), and other Heterodera species; goiter species (Seed gall nematodes), caenorhabditis species (Anguina); stem and leaf nematodes (Stem and foliar nematodes), aphelenchoides (Aphelenchoides) species; trichina (Sting nemades), long tail nematodes (Belonolaimus longicaudatus) and other trichina (Belonolaimus) species; pine nematodes (Pine nemades), pine nematodes (Bursaphelenchus xylophilus) and other Bursaphelenchus (Bursaphelenchus) species; a species of the genus strongylus (Ring nematodes), a species of the genus strongylus (crimonema), a species of the genus strongylus (crimonemella), a species of the genus strongylus (crimonemeides), a species of the genus strongylus (mesomonema); stem and caenorhabditis elegans (Stem and bulb nematodes), rotting stem nematodes (Ditylenchus destructor), caenorhabditis elegans (Ditylenchus dipsaci) and other stem nematode (Ditylenchus) species; a Willonema (Awl nematodos), conus (Dolichodorus) species; spiralis (Spiral nematodes), multi-headed spiralis (Heliocotylenchus multicinctus), and other spiralis (spiralyenchus) species; sheath and sheath nematodes (Sheath and sheathoid nematodes), sheath nematode (hemacyclora) species and hemiwheel nematode (hemcicontoides) species; a submerged root nematode (hirschmanniella) species; a nematode (Lance nematodes), a Corona (Hoploaimus) species; pseudoroot knot nematode (false rootknot nematodes), pearl nematode (nacobus) species; needle nematodes (Needle nematodes), long-shank nematodes (Longidorus elongatus) and other long-shank nematode (longidolus) species; a Pratylenchus species; rotten nematodes (Lesion nematoddes), pratylenchus variabilis (Pratylenchus neglectus), pratylenchus prallensis (Pratylenchus penetrans), pratylenchus curvulus (Pratylenchus curvitatus), pratylenchus colognes (Pratylenchus goodeyi) and other brachyotus species; citrus perforins (Burrowing nematodes), radopholus (Radopholus similis) and other introgressing nematode (Radopholus) species; reniform nematodes (Reniform nematodes), luo Baishi spiral nematodes (Rotylenchus robustus) reniform nematodes (Rotylenchus reniformis) and others a species of the genus stromelitemia (Rotylenchus); a scenedema (Scutellonema) species; a root-worm (Stubby root nematodes), a primitive Bursaphelenchus (Trichodorus primitivus), and other Bursaphelenchus (Trichodorus) species, a Bursaphelenchus (Paratrix dorus) species; stunting nematodes (Stunt nemades), purslane stunting nematodes (Tylenchorhynchus claytoni), cis-trans stunting nematodes (Tylenchorhynchus dubius) and other stunting nematode (tylenchormchus) species; citrus nematodes (Citrus nematodes), piercing nematode (tyrenchus) species; a species of the genus xiphides (Xiphinema); other plant parasitic nematode species, such as the subtrenia species (subunguina spp.), the root knot nematode species (hypsomycete spp.), the macrocyclic nematode species (Macroposthonia spp.), the dwarf nematode species (Melinius spp.), the point cyst species (Punctodera spp.), and the pentadactyla species (quinsulcus spp.).

The compounds of the invention may also have activity against molluscs. Examples thereof include, for example, the family of Pomacea canaliculata; slug family (aris) (black slug (a. Ter), annular slug (a. Circumscript), brown brave slug (a. Hortinsis), red slug (a. Rufus)); barbaceae (Bradybaenidae) (Bush snail (Bradybaena fruticum)); spring onions (Cepaea) (garden spring onions (c.hortens), forest spring onions (c nemorolia)); oxklodina (ochlopdina); wild slug genus (Derocera) (wild ash slug (D. Agrestis), D. Empiricorum, smooth wild slug (D. Laeve), reticulate wild slug (D. Reticum)); disc snail (Discus) (circular disc snail); from wood not (Euomphalia); soil snail (Galba) (kerf soil snail (g.trunk); snails (helicobacter) (itara snail (h.itala), buwei snail (h.obvia)); snail (Helicidae) Helicigona arbustorum); black knot disco (helicodus); snail (Helix) (open snail (h.aperta)); slug genus (Limax) (Li Maike slug (l. Cinereoniger), huangyu (l. Flavus), edge slug (l. Marginalis), large slug (l. Maximus), flexible slug (l. Tenellus)); the genus cone (Lymnaea); milax (minor slug family) (black minor slug (m. Gagates), edge minor slug (m. Marginalis), major minor slug (m sowerbyi)); oncomelania (Opeas); the genus conch (Pomacea) (ampullaria gigas (p.canaticum)); vanilla snail (Vallonia) and zanitodes (Zanitoides).

The active ingredients according to the invention can be used for controlling, i.e. suppressing or destroying, pests of the above-mentioned type, which are present in particular on plants, especially on plants and ornamental plants which are useful in agriculture, in horticulture and in forestry, or on organs such as fruits, flowers, leaves, stems, tubers or roots of such plants, and in some cases plant organs which form even at a later point in time remain protected against these pests.

In particular, suitable target plants or crops are cereals, such as wheat, barley, rye, oats, rice, maize or sorghum; beet, such as sugar beet or fodder beet; fruits, such as pomes, stone fruits or stone-less fruits, such as apples, pears, plums, peaches, apricots, cherries or berries, such as strawberries, raspberries or blackberries; leguminous crops, such as beans, lentils, peas or soybeans; oil crops, such as rape, mustard, poppy, olives, sunflowers, coconuts, castor beans, cocoa beans or groundnuts; melon crops, such as pumpkin, cucumber or melon; fiber plants, such as cotton, flax, hemp or jute; citrus fruits, such as orange, lemon, grapefruit or tangerine; vegetables, such as spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell peppers; lauraceae, such as avocado, cinnamon or camphor; and also tobacco, nuts, coffee, eggplant, sugar cane, tea, pepper, grape vine, hops, plantain, and latex plants.

The compositions and/or methods of the present invention may also be used on any ornamental and/or vegetable crop, including flowers, shrubs, broad-leaved trees and evergreens.

For example, the invention may be used for any of the following ornamental plant species: agastache species, pseudoptera species (Alonsoa spp.), silver lotus species, south africa (Anisodontea capsenisis), chamomile species, chrysosporium species, aster species, begonia species (e.g., begonia, b. Tub reux)), phyllanthus species, yangher species (brachyosome spp.), brassica species (ornamental plant), cattail species, capsicum, vinca, cannabis species, cornflower species, chrysanthemum species, melon species (silver stevia (c. Maritimum)), chrysanthemum species, rhodiola (Crassula coccinea), red calyx flowers (Cuphea ignea), dahlia species, cudweed species, nettle, peonies, balloonflower species (gordonia) fructus forsythiae species, herba Pogostemonis species, herba Erodii murine Aspergillus (Geranium gnaphalium), herba Geranii species, flos Gomphrenae, geranium species, semen Brassicae Junceae species, helianthus species, hibiscus species, and herba Pogostemonis hydrangea species, henbane species (impatiens balsamina), acalypha species (irestines spp.), glabrous species, lantana camara, marshmallow, marjoram, and so forth lion, lily, pine, gourmet, spearmint, longicorn, marigold, carnation (carnation), canna, oxalis, bellflower, pelargonium (pelargonium scum, pelargonium elegans), viola (pansy), pansy (pansy), the plant species may be selected from the group consisting of petunia species, oleander species, bergamot species (plectranthus spp.), poinsettia species, reptile species (petunia, reptile), primula species, buttercup species, azalea species, rose species (rose), flaveria species, african cordierite species, sage species, echinacea (Scaevola aemia), mottlea flowers (Schizanthus wisetonensis), sedum species, solanum species, su Feini petunia species (Surfinia spp.), tagetes species, nicotiana species, verbena species, zinnia species, and other flower pot plants.

For example, the invention may be used with any of the following vegetable species: allium (garlic, onion, allium sativum (A. Oschaninii), allium tuberosum, allium fistulosum), coral, parsley, asparagus, beet, brassica (cabbage, chinese cabbage, turnip), capsicum, peacock, chicory (chicory, endive), watermelon, cucumber (cucumber, melon), pumpkin (pumpkin, indian pumpkin), cynara (artichoke ), carrot, fennel, hypericum, lettuce, tomato (tomato, cherry tomato), boehmeria, basil, parsley, phaseolus (bean, string bean), pea, radish, rheum officinale, rosemary, sage, black salubrion, eggplant, spinach, new valerian (lettuce valerian, V.eriocapa).

Preferred ornamental species include African violet, begonia, dahlia, dadingcha, sparassis, verbena, rosa, kalanchoe, yifuchsin, aster, cornflower, tamarinus, taverum, cuphinia, america, nerium, flabella, crassularia, pelargonium, viola, impatientis, geranium, july, ranunculus, sage, salvia, rosmarinus, salvia, st. Johnswort, peppermint, sweet pepper (sweet peppers), tomato, and cucumber.

These active ingredients according to the invention are particularly suitable for controlling hyacinth bean aphids, cucumber leaf beetles, tobacco budworms, peach aphids, plutella xylostellas and sea ash wing noctuid on cotton, vegetable, maize, rice and soybean crops. These active ingredients according to the invention are furthermore particularly suitable for controlling cabbage loopers (preferably on vegetables), codling moths (preferably on apples), leafhoppers (preferably in vegetables, vineyards), potato leaf beetles (preferably on potatoes) and striped rice borers (preferably on rice).

Compounds having formula I are particularly suitable for control:

pests of the order lepidoptera, for example one or more of the following species: spodoptera littoralis, spodoptera frugiperda, plutella xylostella, cnaphalocrocis medinalis (Cnaphalocrocis medinalis), codling moth, soybean looper (Chrysodeixis includes), chilo suppressalis, corn borer (Elasmopalpus lignosellus), spodoptera frugiperda (Pseudoplusia includens), and tomato leaf miner (preferably on vegetables and corn).

The term "crop" is to be understood as also including crop plants which have been so transformed by the use of recombinant DNA technology that they are capable of synthesizing one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus bacillus.

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 d-endotoxins, e.g., cry1Ab, cry1Ac, cry1F, cry Fa2, cry2Ab, cry3A, cry Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), e.g., vip1, vip2, vip3 or Vip3A; or insecticidal proteins of nematode-parasitic bacteria, such as the species Photorhabdus (Photorhabdus spp.) or Xenorhabdus (Xenorhabdus spp.), such as the species Photorhabdus (Photorhabdus luminescens), xenorhabdus nematophilus (Xenorhabdus nematophilus); toxins produced by animals, such as scorpions, spider toxins, bee toxins, and other insect-specific neurotoxins; toxins produced by fungi, such as streptomycin, lectins (lecins), such as pea lectin, barley lectin or vanishing lotus lectin; lectin (agglutinin); protease inhibitors such as trypsin inhibitor, serine protease inhibitor, patatin, cysteine protease inhibitor, papain inhibitor; ribosome Inactivating Proteins (RIP), such as ricin, maize-RIP, abrin, luffa seed toxin, saporin or curcin; steroid metabolizing enzymes such as 3-hydroxysteroid oxidase, ecdysteroid-UDP-glycosyl-transferase, cholesterol oxidase, ecdysone inhibitor, 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.

In the context of the present invention, d-endotoxins, such as Cry1Ab, cry1Ac, cry1F, cry Fa2, cry2Ab, cry3A, cry Bb1 or Cry9C, or vegetative insecticidal proteins (Vip), such as Vip1, vip2, vip3 or Vip3A, are understood to obviously also include mixed toxins, truncated toxins and modified toxins. Hybrid toxins are recombinantly produced by a new combination of different domains of those proteins (see, e.g., WO 02/15701). Truncated toxins, such as truncated Cry1 abs, are known. In the case of modified toxins, one or more amino acids of the naturally occurring toxin are replaced. In such amino acid substitutions, it is preferred to insert non-naturally occurring protease recognition sequences into the toxin, such as, for example, in the case of Cry3A055, cathepsin-G-recognition sequences into the Cry3A toxin (see WO 03/018810).

Examples of such toxins or transgenic 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.

Methods for preparing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above. CryI-type deoxyribonucleic acids and their preparation are known, for example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO 90/13651.

Toxins contained in transgenic plants render the plants tolerant to harmful insects. Such insects may be present in any insect taxa, but are particularly common in beetles (coleoptera), diptera (diptera), and moths (lepidoptera).

Transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are known and some of them are commercially available. Examples of such plants are:(maize variety, table)To Cry1Ab toxin); YIELdGard->(maize variety, expressing Cry3Bb1 toxin); YIELdGard->(maize variety, expressing Cry1Ab and Cry3Bb1 toxins); />(maize variety, expressing Cry9C toxin); herculex->(maize variety, enzyme phosphinothricin N-acetyl transferase (PAT) expressing Cry1Fa2 toxin and obtaining tolerance to herbicide glufosinate); nuCOTN->(cotton variety, expressing Cry1Ac toxin); bollgard->(cotton variety, expressing Cry1Ac toxin); bollgard->(cotton varieties expressing Cry1Ac and Cry2Ab toxins); />(cotton variety, expressing Vip3A and Cry1Ab toxins); />(potato variety, expressing Cry3A toxin); GT Advantage (GA 21 resistant to glyphosatePhosphine trait)/(l)>CB Advantage (Bt 11 Corn Borer (CB) trait) >

Further examples of such transgenic crops are:

bt11 maize from the seed company of Fangzha (Syngenta Seeds SAS), path Huo Bite (Chemin de l' Hobit) 27, F-31 st. Su Weier (St. Sauveur), france accession number C/FR/96/05/10. Genetically modified maize is rendered resistant to attack by european corn borer (corn borer and cnaphalocrocis medinalis) by transgenic expression of truncated Cry1Ab toxins. Bt11 maize also transgenically expresses the enzyme PAT to obtain tolerance to the herbicide glufosinate.

Bt176 corn from seed of Fangzha, huo Bite, line 27, F-31 790 san Su Weier, france accession number C/FR/96/05/10. Genetically modified maize, genetically expressed as a Cry1Ab toxin, is resistant to attack by european corn borers (corn borers and cnaphalocrocis medinalis). Bt176 maize also transgenically expresses the enzyme PAT to obtain tolerance to the herbicide glufosinate.

MIR604 corn from seed of Fangda, huo Bite, line 27, F-31 790, sheng Su Weier, france, accession number C/FR/96/05/10. Corn that is rendered insect-resistant by transgenic expression of the modified Cry3A toxin. This toxin is Cry3A055 modified by insertion of a cathepsin-G-protease recognition sequence. The preparation of such transgenic maize plants is described in WO 03/018810.

MON 863 corn from Monsanto Europe S.A.), 270-272 Teflon (Avenue DE Tervuren), B-1150 Brussels, belgium, accession number C/DE/02/9.MON 863 expresses a Cry3Bb1 toxin and is resistant to certain coleopteran insects.

IPC 531 cotton from Mengshan European company, 270-272 Teflon, B-1150 Brussels, belgium, accession number C/ES/96/02.

6.1507 maize, from pioneer overseas company (Pioneer Overseas Corporation), tedelsco, avenue Tedesco, 7B-1160 Brussels, belgium, accession number C/NL/00/10. Genetically modified maize, expressing the protein Cry1F to obtain resistance to certain lepidopterans, and PAT protein to obtain tolerance to the herbicide glufosinate.

NK603×MON 810 maize from Mengshan European company 270-272 Teflon, B-1150 Brussels, belgium under accession number C/GB/02/M3/03. By crossing the genetically modified varieties NK603 and MON 810, it is composed of a conventionally bred hybrid maize variety. NK603 xMON 810 maize transgenically expresses the protein CP4 EPSPS obtained from Agrobacterium strain CP4, rendering it herbicide resistant (containing glyphosate) and also Cry1Ab toxins obtained from Bacillus thuringiensis subspecies kurstaki, render them resistant to certain lepidopteran insects, including European corn borers.

Transgenic crops of insect-resistant plants are also described in BATS (biosafety and sustainable development center (Zentrum f u r Biosicherheit und Nachhaltigkeit), BATS center (Zentrum BATS), classification Cui She (Clarastrasse) 13, 4058 Basel (Basel), switzerland) report 2003%http://bats.ch) Is a kind of medium.

The term "crop" is understood to also include crop plants which have been transformed in such a way by using recombinant DNA techniques that they are capable of synthesizing selectively acting antipathogenic substances, such as, for example, so-called "disease-associated proteins" (PRP, see, for example, EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesizing such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818 and EP-A-0 353191. Methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

Crops can also be modified to increase resistance to fungal (e.g., fusarium, anthracnose, or phytophthora), bacterial (e.g., pseudomonas), or viral (e.g., potexvirus, tomato spotted wilt virus, cucumber mosaic virus) pathogens.

Crops also include those having increased resistance to nematodes (e.g., heterodera glycines).

Crops with tolerance to abiotic stress include those with increased tolerance to drought, high salt, high temperature, cold, frost or light radiation, for example by expression of NF-YB or other proteins known in the art.

The anti-pathogenic substances that can be expressed by such transgenic plants include, for example, ion channel blockers, such as blockers of sodium and calcium channels, e.g., viral KP1, KP4 or KP6 toxins; stilbene synthase; bibenzyl synthase; chitinase; glucanase; so-called "disease process related proteins" (PRP; see e.g.EP-A-0 392 225); an anti-pathogenic substance produced by a microorganism, such as a peptide antibiotic or a heterocyclic antibiotic (see, e.g., WO 95/33818) or a protein or polypeptide factor involved in plant pathogen defense (so-called "plant disease resistance gene", as described in WO 03/000906).

Further areas of use of the compositions according to the invention are the protection of stored articles and storage compartments and of raw materials such as wood, textiles, floors or buildings, and also in the hygiene sector, in particular the protection of humans, domestic animals and productive livestock from pests of the type mentioned.

The present invention provides a compound of the second aspect for use in therapy. The present invention provides a compound of the first aspect for controlling parasites in or on an animal. The invention further provides a compound of the first aspect for controlling ectoparasites in animals. The present invention further provides a compound of the first aspect for use in the prevention and/or treatment of diseases transmitted by ectoparasites.

The present invention provides the use of a compound of the second aspect for the manufacture of a medicament for controlling parasites in or on an animal. The invention further provides the use of a compound of the first aspect for the manufacture of a medicament for controlling ectoparasites in animals. The invention further provides the use of a compound of the first aspect for the manufacture of a medicament for the prevention and/or treatment of diseases transmitted by ectoparasites.

The present invention provides the use of a compound of the first aspect for controlling parasites in or on an animal. The invention further provides the use of a compound of the second aspect for controlling ectoparasites in animals.

The term "control" when used in the context of parasites in or on animals means to reduce the number of pests or parasites, eliminate pests or parasites and/or prevent further pest or parasite infestation.

The term "treating" when used in the context of parasites in or on an animal is meant to inhibit, slow, stop or reverse the progression or severity of an existing symptom or disease.

The term "preventing" when used in the context of parasites in or on animals refers to avoiding developing symptoms or diseases in the animal.

The term "animal" when used in the context of parasites in or on animals may refer to mammals and non-mammals, such as birds or fish. In the case of a mammal, it may be a human or non-human mammal. Non-human mammals include, but are not limited to, livestock animals and pets. Livestock animals include, but are not limited to, cattle, camels, pigs, sheep, goats, and horses. Pets include, but are not limited to, dogs, cats, and rabbits.

A "parasite" is a pest that lives in or on the body of a host animal and benefits by harvesting nutrients at the expense of the host animal. An "endoparasite" is a parasite that lives within the body of a host animal. An "ectoparasite" is a parasite that lives on the surface of a host animal. Ectoparasites include, but are not limited to ticks, insects, and crustaceans (e.g., sea lice). The subclasses ticks (or acarina) include ticks and mites. Ticks include, but are not limited to, members of the following genera: rhipicephalus (rhipicephalus), such as rhipicephalus (Rhipicaphalus microplus) (rhipicephalus (Boophilus microplus)) and rhipicephalus hemangiocarpus (Rhipicephalus sanguineus); chlorpyrifos (amblyomra); leather tick (Dermacentor); haemaphysalis (Haemaphysalis); glehnia (Hyalomma); hard ticks (Ixodes); rhipicephalus (Rhipicer); cattle ticks (Margaropus); the genus Alnus (Argas); otobius (Otobius); the genus tick (Ornithiodoros). Mites include, but are not limited to, members of the following genera: dermatophagoides, such as, for example, dermatophagoides pteronyssinus (chord bovis); itch mite genus such as, for example, itch mite of sheep (Psoropates ovis); agaricus (cheyletidella); dermatophagoides (dermanssus); such as dermatophagoides pteronyssinus (Dermanyssus gallinae); avian tetranychus (Ortnithonyssus); demodex mite (Demodex anis); scabies, such as human scabies (Sarcoptes scabiei); sore mite genus (Psorergates). Insects include, but are not limited to, members of the following objectives: flea, diptera, pubic, lepidoptera, coleoptera, and homoptera. Members of the order of the flea include, but are not limited to, chlamydia felis (Ctenocephalides felis) and Chlamydia canis (Ctenocephatides canis). Members of diptera include, but are not limited to, the genus Musca spp; skin flies, such as horse flies (Gasterophilus intestinalis) and sheep flies (Oestrus ovis); chelating flies; tabanus species, such as Tabanus spp (haematopta spp.) and Tabunus species; black horn flies, such as bot flies (haematobia irritans); stings genus (Stomoxys); green flies (Lucilia); midges; and (3) mosquitoes. Members of the class of pubescens include, but are not limited to, sucking lice and chewing lice (ovicola lice), such as ovicola Ovis (Bovicola Ovis) and bovine lupulus (Bovicola Ovis).

The term "effective amount" when used in the context of parasites in or on an animal means the amount or dose of a compound of the invention or a salt thereof which, when administered to the animal in a single dose or multiple doses, provides the desired effect in or on the animal. The effective amount can be readily determined by the attending diagnostician (as one skilled in the art) by the use of known techniques and by observing results obtained under analogous circumstances. In determining an effective amount, the attending diagnostician considers a number of factors, including, but not limited to: species of mammal; its body shape, age and general health; the parasite and the degree of infestation to be controlled; the particular disease or condition involved; the extent or severity of the disease or condition; individual response; the particular compound being administered; mode of administration; bioavailability characteristics of the administered formulation; the selected dosing regimen; concomitant use of a drug; and other related conditions.

The compounds of the invention may be administered to animals by any route having the desired effect, including but not limited to topical, oral, parenteral and subcutaneous. Topical application is preferred. Formulations suitable for topical application include, for example, solutions, emulsions and suspensions, and may take the form of pouring, dispensing, spraying, spray bar (spray pattern) or dipping. In the alternative, the compounds of the invention may be administered via an ear tag or collar.

Salt forms of the compounds of the invention include both pharmaceutically acceptable salts and veterinarily acceptable salts, which may be different from agrochemically acceptable salts. Pharmaceutically and veterinarily acceptable salts and common methods for preparing them are well known in the art. See, e.g., gould, P.L. "Salt selection for basic drugs [ salt selection of base drug ]", international Journal of Pharmaceutics [ J.International pharmacy ],33:201-217 (1986); bastin, R.J. et al, "Salt Selection and Optimization Procedures for Pharmaceutical New Chemical Entities [ salt selection and optimization procedure for New pharmaceutical chemical entity ]", organic Process Research and Development [ organic Process research and development ],4:427-435 (2000); and Berge, S.M. et al, "Pharmaceutical Salts [ pharmaceutically acceptable salts ]", journal of Pharmaceutical Sciences [ journal of pharmaceutical science ],66:1-19, (1977). Those skilled in the art of synthesis will appreciate that the compounds of the present invention are readily converted to salts and can be isolated as salts, such as hydrochloride salts, using techniques and conditions well known to those of ordinary skill in the art. In addition, one skilled in the art of synthesis will appreciate that the compounds of the present invention are readily converted to the corresponding free base and can be isolated as the corresponding free base from the corresponding salt.

The invention also provides a method for controlling pests (such as mosquitoes and other disease vectors; see also http:// www.who.int/malaria/vector_controls/irs/en /). In one embodiment, the method for controlling pests includes applying the composition of the invention to the target pests, to their locus, or to a surface or substrate by brushing, rolling, spraying, spreading or dipping. By way of example, IRS (indoor hold-up spray) application of a surface (such as a wall, ceiling or floor surface) is contemplated by the method of the present invention. In another embodiment, it is contemplated that such compositions are applied to a substrate, such as a nonwoven or fabric material in the form of a netting, a coating, bedding, curtains, and tents (or may be used in the manufacture of such articles).

In one embodiment, a method for controlling such pests comprises applying to the target pests, to their locus, or to a surface or substrate a pesticidally effective amount of a composition of the invention so as to provide effective residual pesticidal activity on the surface or substrate. Such application may be by brushing, rolling, spraying, spreading or dipping the pesticidal composition of the present invention. By way of example, IRS application to a surface (e.g., a wall, ceiling or floor surface) is contemplated by the methods of the present invention to provide effective residual pesticidal activity on the surface. In another embodiment, application of such compositions for residual control of pests on substrates such as textile materials in the form of netting, coverings, bedding, curtains, and tents (or may be used in the manufacture of such articles) is contemplated.

The substrate to be treated (including nonwoven, woven or netting) may be made of natural fibers such as cotton, raffia leaf fibers, jute, flax, sisal, hemp or wool, or synthetic fibers such as polyamide, polyester, polypropylene, polyacrylonitrile, or the like. Polyesters are particularly suitable. Methods of textile treatment are known, for example WO 2008/151984, WO 2003/034823, US 5631072, WO 2005/64072, WO2006/128870, EP 1724392, WO 2005113886 or WO 2007/090739.

Further areas of use of the composition according to the invention are in the field of tree injection/trunk treatment for all ornamental trees and all kinds of fruit trees and nut trees.

In the field of tree injection/trunk treatment, the compounds according to the invention are particularly suitable for combating wood-boring insects from the orders lepidoptera and from the order coleoptera as mentioned above, in particular the woodworms listed in tables a and B below:

table a. Examples of extraneous woodworms of economic importance.

Table b. examples of local woodworms of economic importance.

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The invention can also be used to control any insect pest that may be present in turf grass, including, for example, beetles, caterpillars, fire ants, ground pearls (ground pearls), armyworms, hygrophilas, mites, mole cricket, scale, mealybugs, ticks, cicada, southern wheat bugs, and grubs. The present invention can be used to control insect pests, including eggs, larvae, nymphs, and adults, at various stages of their life cycle.

In particular, the invention may be used to control insect pests that are fed with roots of turf grass, including grubs (e.g., round head turtles (cyclopla spp.) (e.g., labeled turtles, c. Lurida), rhizomotgus (e.g., european turtles, european root-cutting turtles (r. Majalis)), cotinus (e.g., green june beetles (Green June beetle), c. Nitida), arctic turtles (poillia spp.) (e.g., japanese beetles, tortoise beetles (p. Japonica)), gill hornworms (Phyllophaga spp.) (e.g., five month/six month beetles), ataenis (e.g., turtles (Black turfgrass Ataenius), a. Return), metal (Maladera spp.) (e.g., asia beetle (Asiatic garden beetle), m. Castanera) and cricket (cricket) and yellow mosquito, and yellow mosquito (sepia spp.) (yellow mosquito) and yellow mosquito species (yellow mosquito) and yellow mosquito (yellow mosquito) spp. (yellow mosquito sp.) and yellow mosquito spp.35).

The invention can also be used to control insect pests of turf grass in couch houses including armyworms such as Qiu Yee (fall armyworm) spodoptera frugiperda, and the common armyworm Pseudaletia unipuncta, root-cutting worms such as the species cryptosporidium spinosum, such as the species s.ventus verstinus and the species beak of forage grass (s.parvulus), and meadow moth such as the species Crambus spp and tropical meadow moth Herpetogramma phaeopteralis.

The invention can also be used to control insect pests in turf grass living on the ground and feeding turf grass leaves, including wheat bugs (such as southern wheat bugs, southern lygus (Blissus insularis)), bermuda mites (Bermudagrass mite) (Eriophyes cynodoniensis), meadow grass meadow (Antonina graminis)), swamp hoppers (Propsapia bicincta), leafhoppers, rootworm (nocturnal), and wheat binary aphids.

The invention can also be used to control other pests in turf grass, such as exotic solenopsis invicta (Solenopsis invicta) which creates a formicary in the turf.

In the hygiene sector, the compositions according to the invention are effective against ectoparasites such as hard ticks, soft ticks, scabies, autumn mites, flies (biting and licking), parasitic fly larvae, lice, hair lice, bird lice and fleas.

Examples of such parasites are:

nits order: the genus psyllium, the genus nit (lineginaphus spp.), the genus pediculus, the genus pubescent (phthirus spp.), the genus pediculus.

Food order: hairiness species, short hairiness species, duck species, bovine hairiness species, virNickela (Werneckiella spp.), lai Pi Kente Rollen species (Lepikentron spp.), beast species, chouioia species (Felicola spp.).

Diptera and longicotina (Nematomyces) and Brevibacterium (Brachymyces), such as Aedes spp, analae, culex spp, simian, eusium, juglans, jutser, phlebotomus, lutzomyces, jutswing, jutshellia, jutser, tabanus, huang Meng, tabanus, nubanus, jutsca, apostica, periomyza, and Musca spp the plant species may be selected from the group consisting of a odontophaga species (hydraea spp.), a chelating species, a black horn species (haemaggl spp.), a mophaga species (Morellia spp.), a toilet spp., a bennia spp., a Glossina spp, a blowfly species (calphos spp.), a green fly species (Lucilia spp.), a Chrysomyia spp), a chrysomya spp, a sedge spp, a mackeromya spp, a crazy fly species (oerstripe spp), a dermatophagomya spp, a Hypoderma spp, a gaster spp, a hippcopp, a hippcopsis spp, a copperus spp, a coppica spp, and a coppica spp Sheep lice species (lipotenea spp.) and tick fly species (Melophagus spp.).

The order of the fleas (Siphonapterida), for example, the genus flea (Pulex spp.), the genus flea, the genus chebya (xenopsyla spp.), the genus flea.

Heteroptera (Heteropterida), such as, for example, a bed bug species, a trypanosoma species, a red stinkbug species, a trypanosoma species (panstrongyles spp.).

Blattaria (blattaria), such as blattaria orientalis (Blatta orientalis), periplaneta americana (Periplaneta americana), german cockroach (blattelagermannia), and blattaria species (Supella spp.) of Xia Baila.

Acarina (Acaria) and Bactrocera (Meta-stingmata) and Strophaga (Meema-stingmata) such as, for example, the species of Ornithina (Argas spp.), the species of Bluntouche (Ornithovorus spp.), the species of Auricularia (Otobius spp.), the species of hard tick (Ixodes spp.), the species of Blumeria (Amblyomma spp.), the species of Bopyris (Boophulus spp.), the species of Derman (Dermacor spp.), the species of Rhemophilus (Haemophilus spp.), the species of Hyaloma (Hyaloma spp.), the species of Rhipicephalus (Rhipophagus spp.), the species of Dermatophagus (Dermatophagus spp.), the species of Rhipicephalus spp. And the species of Vaccinum spp.

The order axomedes (Actinedida) (Prostigmata) and the order anatida (anamata), such as the species of the genus Aphanus (Acarapis spp.), the species of the genus Acarina (Cheylella spp.), the species of the genus Acarina (Ornithecyleta spp.), the species of the genus Myrobia (Myobasphp.), the species of the genus Pythagoreae (Psorergates spp.), the species of Demodex spp, the species of the genus Acalycemia (Trogrip spp.), the species of the genus Yak (Litrophos spp.), the species of the genus Acarina (Acarina spp.), the species of the genus Tyrophagus (Tyrochanus spp), the species of the genus Trichophytosis (Caloglyphiphus spp), the species of the species under the neck (Hypodects spp.), the species of the genus Pterosphaerella (Pterosphaerosphp), the species of the genus Demodex spp (Psorophylus spp), the species of the genus Demodex, the species of the genus Demodex (Cyclopentas spp), the species of the genus Cyclopyra (Cyclopentas spp), the species of the genus Cyclopentades (Cytophagus spp), the species of the genus Cyclopentanus, the species of the genus Cytophagus (Cytophagus spp).

The compositions according to the invention are also suitable for protecting against insect infestation in the case of materials such as wood, textiles, plastics, adhesives, glues, lacquers, papers and cards, leather, floors and buildings.

The composition according to the invention can be used, for example, against the following pests: beetles, such as North America beetles (Hylotrupes bajulus), length Mao Tianniu (Chlorophorus pilosis), amomum tsugae (Anobium punctatum), red Mao Qie beetles (Xestobium rufovillosum), amomum combinarum (Ptilinusci), dendrobium pertinex, amomum pinnata (Ernobius molllis), priobium carpini, broccoli (Lyctus brunneus), amomum africanum (Lyctus africanus), amomum southern (Lyctus planicollis), amomum oak (Lyctus lineris), amomum japonicum (Lyctus pubescens), amomum chest (Trogoxylon aequale), lepidium (Minthesrugilis), amomum species (Xylebos spec), amomum species (Trypodendron spec), coffee longus (Apate monaus), amomum melegueta (Bostrychus capucins), amomum heteropterus (Lepidium), amomum (Flex longum) and Siberian (Dinoderus minutus), and also membranous species such as, for example, black wasps (Sirex juntus), hornet (Urocerus gigas), taenius (Urocerus gigas taignus) and Urocerus augu, and termites such as, for example, european wood termites (Kalotermes flavicollis), max-tip sand termites (Cryptotermes brevis), indonesia (Heterotermes indicola), yellow-chest termites (Reticulitermes flavipes), sang Tesan termites (Reticulitermes santonensis), european termites (Reticulitermes lucifugus), dahlculture termites (Mastotermes darwiniensis), neHuada termites (Zootermopsis nevadensis) and domestic termites (Coptotermes formosanus), and moths, such as tuna (Lepisma saccharina).

The compounds having formula I or salts thereof are particularly suitable for controlling one or more pests selected from the order lepidoptera, in particular one or more of the following species: spodoptera littoralis, spodoptera frugiperda, plutella xylostella, cnaphalocrocis medinalis, codling moth, geometrid on beans, chilo suppressalis, corn borer on south america, spodoptera frugiperda, and spodoptera frugiperda (preferably on vegetables and corn). In a preferred embodiment of each aspect, compound TQ (wherein the abbreviation "TQ" means "one compound selected from the group consisting of list Q and the compounds defined in table X, table Xa and table P") controls one or more of the following species of pest selected from: spodoptera littoralis, spodoptera frugiperda, plutella xylostella, cnaphalocrocis medinalis, codling moth, geometrid on beans, chilo suppressalis, corn borer on south america, spodoptera frugiperda, and spodoptera frugiperda (preferably on vegetables and corn).

The compounds of formula I or salts thereof are particularly suitable for controlling one or more of diamide-resistant insects selected from the group consisting of: spodoptera littoralis, spodoptera frugiperda, plutella xylostella, cnaphalocrocis medinalis, codling moth, geometrid of soybean, chilo suppressalis, corn borer of south america, spodoptera frugiperda, and leaf miner of tomato. In a preferred embodiment of each aspect, compound TQ (wherein the abbreviation "TQ" means "one compound selected from the group consisting of list Q and the compounds defined in table X, table Xa and table P") controls one or more of the diamide resistant insects: spodoptera littoralis, spodoptera frugiperda, plutella xylostella, cnaphalocrocis medinalis, codling moth, geometrid of soybean, chilo suppressalis, corn borer of south america, spodoptera frugiperda, and leaf miner of tomato.

The compounds of formula I or salts thereof are particularly suitable for controlling one or more of diamide-resistant insects selected from the group consisting of: plutella xylostella, chilo suppressalis, and tomato leaf miner.

In a preferred embodiment of each aspect, compound TQ (where the abbreviation "TQ" means "one compound selected from the group consisting of list Q and the compounds defined in table X, table Xa and table P") controls one or more insects selected from the group consisting of plutella xylostella, chilo suppressalis and tomato leaf miner, which insects exhibit resistance to IRAC MoA group 28 insecticides such as plutella xylostella+tq, chilo suppressalis+tq, and tomato leaf miner+tq.

The compounds according to the invention may have any number of benefits, including in particular advantageous levels of biological activity towards protecting plants against insects or superior properties for use as agrochemical active ingredients (e.g. higher biological activity, advantageous activity profile, increased safety (against non-target organisms (such as fish, birds and bees) above and below ground), improved physico-chemical properties, or increased biodegradability). In particular, it has been unexpectedly found that certain compounds having formula I can exhibit advantageous safety against non-target arthropods, particularly pollinators (such as bees, solitary bees and bumblebees). Most particularly, it is relative to italian bees (Apis mellifera).

The compounds according to the invention can be used as pesticides in unmodified form, but they are generally formulated into compositions in a variety of ways using formulation aids such as carriers, solvents and surface-active substances. These formulations may be in different physical forms, for example, in the following forms: dust, gels, wettable powders, water dispersible granules, water dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifyable concentrates, oil-in-water emulsions, flowable oils, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water soluble concentrates (with water or water miscible organic solvents as a carrier), impregnated polymeric films or in other forms known, for example, from Manual on Development and Use of FAO and WHO Specifications for Pesticides [ handbook of FAO and WHO standards for pesticides ], united nations, 1 st edition, second revision (2010). Such formulations may be used directly or may be diluted before use for reuse. Dilution may be performed with, for example, water, liquid fertilizer, micronutrients, biological organisms, oil or solvents.

These formulations can be prepared, for example, by mixing the active ingredient with formulation auxiliaries in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. These active ingredients may also be formulated with other adjuvants such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.

These active ingredients may also be contained in very fine microcapsules. The microcapsules contain the active ingredient in a porous carrier. This enables the active ingredient to be released (e.g., slowly released) into the environment in controlled amounts. The microcapsules typically have a diameter of from 0.1 to 500 microns. They contain the active ingredient in an amount of from about 25% to 95% by weight of the capsule. These active ingredients may be in the form of monolithic solids, in the form of fine particles in solid or liquid dispersions, or in the form of suitable solutions. The encapsulated film may comprise, for example, natural or synthetic rubber, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyester, polyamide, polyurea, polyurethane or chemically modified polymer, or other polymers known to those skilled in the art. Alternatively, very fine microcapsules may be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of the base material, but these microcapsules are not themselves encapsulated.

Formulation auxiliaries suitable for preparing the compositions according to the invention are known per se. As the liquid carrier, use can be made of: water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1, 2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol rosinate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N, N-dimethylformamide, dimethyl sulfoxide, 1, 4-dioxane, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, dipropylene glycol, alkylpyrrolidones, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isopentyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, N-hexane, N-octylamine, stearic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, and the like.

Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cotton seed hulls, wheat flour, soybean flour, pumice, wood flour, ground walnut hulls, lignin and the like.

A large amount of surface-active substances can be advantageously used in both solid and liquid formulations, especially those formulations which can be diluted by a carrier before use. The surface-active substances may be anionic, cationic, nonionic or polymeric and they may be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium dodecyl sulfate; salts of alkylaryl sulfonates such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products such as ethoxylated nonylphenols; alcohol/alkylene oxide addition products, such as ethoxylated tridecyl alcohol; soaps, such as sodium stearate; salts of alkyl naphthalene sulfonates such as sodium dibutyl naphthalene sulfonate; salts of dialkyl sulfosuccinates, such as sodium di (2-ethylhexyl) sulfosuccinate; sorbitol esters such as sorbitol oleate; quaternary amines 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 mono-and di-alkyl phosphates; and also other substances, such as described in: mcCutcheon' sDetergents and Emulsifiers Annual [ Mascin cleaner and emulsifier yearbook ], MC Publishing company (MC Publishing Corp.), richwood, N.J. (Ridgewood New Jersey) (1981).

Additional adjuvants that may be used in the pesticide formulation include crystallization inhibitors, viscosity modifiers, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, substances and buffers that neutralize or alter the pH, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, glidants, lubricants, dispersants, thickeners, anti-freezing agents, microbiocides, and liquid and solid fertilizers.

The composition according to the invention may comprise additives comprising oils of vegetable 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 composition according to the invention is generally from 0.01% to 10% based on the mixture to be applied. For example, the oil additive may be added to the spray tank at the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral or vegetable-derived oils, such as rapeseed oil, olive oil or sunflower oil; emulsified vegetable oil; alkyl esters of oils of vegetable origin, such as methyl derivatives; or oils of animal origin, such as fish oil or tallow. Preferred oil additives include C ₈ -C ₂₂ Alkyl esters of fatty acids, especially C ₁₂ -C ₁₈ Methyl derivatives of fatty acids, such as methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are derived from Compendium of Herbicide Adjuvants [ herbicide adjuvant outline ]]Edition 10, university of south illinois, 2010.

The composition of the invention generally comprises from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of a compound of the invention and from 1 to 99.9% by weight of a formulation aid, preferably comprising from 0 to 25% by weight of a surface-active substance. Whereas commercial products may preferably be formulated as concentrates, the end user will typically employ a dilute formulation.

The application rate varies within a wide range and depends on the nature of the soil, the application method, the crop plant, the pests to be controlled, the prevailing climatic conditions, and other factors which are governed by the application method, the application time and the target crop. Generally, the compounds may be applied at a rate of from 1l/ha to 2000l/ha, especially from 10l/ha to 1000 l/ha.

Preferred formulations may have the following composition (in weight%):

Emulsifiable concentrate：

Active ingredients: 1% to 95%, preferably 60% to 90%

And (2) a surfactant: 1% to 30%, preferably 5% to 20%

A liquid carrier: 1% to 80%, preferably 1% to 35%

Dust agent：

Active ingredients: 0.1% to 10%, preferably 0.1% to 5%

Solid carrier: 99.9% to 90%, preferably 99.9% to 99%

Suspension concentrate:

active ingredients: 5% to 75%, preferably 10% to 50%

Water: 94% to 24%, preferably 88% to 30%

And (2) a surfactant: 1% to 40%, preferably 2% to 30%

Wettable powder：

Active ingredients: 0.5% to 90%, preferably 1% to 80%

And (2) a surfactant: 0.5% to 20%, preferably 1% to 15%

Solid carrier: 5% to 95%, preferably 15% to 90%

The granule comprises the following components:

active ingredients: 0.1% to 30%, preferably 0.1% to 15%

Solid carrier: 99.5% to 70%, preferably 97% to 85%

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

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The combination is thoroughly mixed with these adjuvants and the mixture is thoroughly ground in a suitable mill to give a wettable powder which can be diluted with water to give a suspension of the desired concentration.

Powder for dry seed treatment	a)	b)	c)
				Active ingredient	25％	50％	75％
Light mineral oil	5％	5％	5％
				Highly dispersed silicic acid	5％	5％	-
Kaolin clay	65％	40％	-
				Talc	-		20％

The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable grinder to give a powder which can be used directly for seed treatment.

Emulsifiable concentrate
		Active ingredient	10％
Octyl phenol polyglycol ether (4-5 mol of ethylene oxide)	3％
		Dodecyl benzene sulfonic acid calcium salt	3％
Castor oil polyglycol ether (35 mol of ethylene oxide)	4％
		Cyclohexanone	30％
Xylene mixture	50％

Emulsions with any desired dilution that can be used in plant protection can be obtained from such concentrates by dilution with water.

Dust agent	a)	b)	c)
				Active ingredient	5％	6％	4％
Talc	95％	-	-
				Kaolin clay	-	94％	-
Mineral filler	-	-	96％

The ready-to-use dust is obtained by mixing the combination with a carrier and grinding the mixture in a suitable grinder. Such powders may also be used for dry dressing of seeds.

Extruder granule
		Active ingredient	15％
Sodium lignin sulfonate	2％
		Carboxymethyl cellulose	1％
Kaolin clay	82％

The combination is mixed and ground with these adjuvants and the mixture is moistened with water. The mixture is extruded and then dried in an air stream.

Coated granule
		Active ingredient	8％
Polyethylene glycol (molecular weight 200)	3％
		Kaolin clay	89％

This finely ground combination is applied uniformly in a mixer to kaolin wet with polyethylene glycol. In this way dust-free coated granules are obtained.

Suspension concentrate

Active ingredient	40％
		Propylene glycol	10％
Nonylphenol polyethylene glycol ether (15 mol of ethylene oxide)	6％
		Sodium lignin sulfonate	10％
Carboxymethyl cellulose	1％
		Silicone oils (in the form of a 75% emulsion in water)	1％
Water and its preparation method	32％

The finely ground combination is intimately mixed with the adjuvants to give a suspension concentrate from which any desired dilution of the suspension can be obtained by dilution with water. With such dilutions, living plants and plant propagation material can be treated and protected against microbial infestation by spraying, watering or dipping.

Flowable concentrate for seed treatment

The finely ground combination is intimately mixed with the adjuvants to give a suspension concentrate from which any desired dilution of the suspension can be obtained by dilution with water. With such dilutions, living plants and plant propagation material can be treated and protected against microbial infestation by spraying, watering or dipping.

Sustained release capsule suspension

28 parts of the combination are mixed with 2 parts of aromatic solvent and 7 parts of 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 defoamer and 51.6 parts of water until the desired particle size was reached. To this emulsion was added 2.8 parts of a 1, 6-hexamethylenediamine mixture in 5.3 parts of water. The mixture was stirred until the polymerization was completed. The capsule suspension obtained is stabilized by adding 0.25 parts of thickener and 3 parts of dispersant. The capsule suspension formulation contains 28% active ingredient. The diameter of the media capsule is 8-15 microns. The resulting formulation is applied as an aqueous suspension to seeds in a device suitable for the purpose.

Formulation types include Emulsion Concentrates (EC), suspension Concentrates (SC), suspoemulsions (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 (oil miscible flowable) (OF), oil-soluble solutions (OL), soluble concentrates (SL), ultra-low volume Suspensions (SU), ultra-low volume solutions (UL), parent drugs (TK), dispersible Concentrates (DC), wettable Powders (WP), soluble Granules (SG) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

Preparation example:

"Mp" means the melting point in degrees Celsius. The radical represents a methyl group. Recording on a Brucker400MHz spectrometer ¹ H NMR measurements give chemical shifts in ppm relative to TMS standard. The spectra were measured in deuterated solvents as indicated. These compounds were characterized using any of the following LC-MS methods. The characteristic LC-MS values obtained for each compound are the retention time ("Rt", recorded in minutes) and the molecular ion (M+H) measured ⁺ 。

LC-MS and GC-MS methods:

LC-MS method 1:

spectra were recorded on a mass spectrometer (SQD, SQDII single quadrupole mass spectrometer) from Waters, equipped with an electrospray source (polarity: positive and negative ions, capillary: 3.00kV, cone aperture range: 30V, extractor: 2.00V, source temperature: 150 ℃, desolvation temperature: 350 ℃, cone aperture gas flow: 50l/h, desolvation gas flow: 650l/h, mass range: 100 to 900 Da) and Acquity UPLC from Waters: binary pumps, heated column chambers, diode array detectors, and ELSD detectors. Column: waters UPLC HSS T3,1.8 μm,30x 2.1mm, temperature: 60 ℃, 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, within 1.2 min; flow (ml/min) 0.85

LC-MS method 2:

spectra were recorded on an acquisition mass spectrometer (SQD or SQDII single quadrupole mass spectrometer) from waters company equipped with electrospray source (polarity: positive or negative ions), capillary: 3.0kV, taper hole: 30V, extractor: 3.00V, source temperature: desolvation temperature at 150 ℃): 400 ℃, taper hole gas flow: 60L/hr, desolvation gas flow: 700L/hr, mass range: 140 to 800 Da) and an acquisition UPLC from waters, with solvent degasser, binary pump, heated column chamber, and diode array detector. Column: waters UPLC HSS T3,1.8 μm,30x 2.1mm, temperature: 60 ℃, DAD wavelength range (nm): 210 to 400, solvent gradient: a = water/methanol 9:1+0.1% formic acid, B = acetonitrile+0.1% formic acid, gradient: 0% -100% B, within 2.5 min; the flow rate (ml/min) was 0.75.

GC-MS method 3:

GC-MS was performed on the following: sammer (Thermo), MS: ISQ, and GC: trace GC 1310 with a column from Saiff Long Feiluo door company (Zebron phenomenex): phase ZB-5ms 15m, diameter: 0.25mm,0.25 μm, he flow 1.5ml/min, syringe temperature: 250 ℃, detector temperature: 220 ℃, the method comprises the following steps: maintaining at 60deg.C for 0.7min,80 deg.C/min up to 320 deg.C, and maintaining at 320 deg.C for 2min for 6min. CI reagent gas: methane flow rate 1ml/min, ionization mode CI, positive polarity, scan time 0.2 seconds, scan mass range 50-650amu

LC-MS method 4:

spectra were recorded on a mass spectrometer (single quadrupole mass spectrometer) from Agilent corporation (Agilent) equipped with multimode electrospray and APCI (polarity: positive and negative ions), capillary: 4.00KV, corona current 4.0 mu A, charging voltage 2.00KV and nitrogen flow rate: 9.0L/min, atomizer pressure: 40psig, mass range: 100 to 1000 m/z), dry gas temperature 250 ℃, evaporator temperature 200 ℃ and spectra were recorded on LCMS from agilent: quaternary pump, heated column chamber, variable wavelength detector. Column: eclipse XDB C18,5.0 μm,150X 4.6mm, column temperature: environment, wavelength (nm): 220nm, solvent: a=0.05% TFA in water and b=0.05% TFA in acetonitrile. Gradient: time/%b: 0/5, 0.5/5, 3.5/90, 5/90, 5.1/5, 7/5; flow rate: 1.0ml/min.

Example 1:6- [ [5- [ (4-chlorophenyl) methoxymethyl ]]-2- (3-chloro-2-pyridinyl) -pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.1)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazol-3-yl]-5-methyl-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.331 mL,4.18mmol,2.00 eq.) in acetonitrile (3.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carboxylic acid (prepared as described in WO 2009/24341 A2) (0.531 g,2.09mmol,1.00 eq.) in acetonitrile (7.0 mL) and pyridine (0.17 mL,2.09mmol,1.0 eq.) at 0 ℃. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (prepared as described in WO 2009/24341 A2) (0.400 g,2.09mmol, 1.00) in acetonitrile (10.9 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.34 mL,4.18mmol,2.00 eq). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was then diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane/ethanol 3:1) to give the desired product 7- [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time 0.94min, m/z 409[ M+H ] ⁺ ]。

Step 2:6- [ [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.320 g,0.783mmol,1.00 eq.) in N, N-dimethylformamide (1.57 mL) was added ammonium acetate (0.181 g,2.35mmol,3 eq.). The reaction mixture was stirred at 50℃for 1 hour. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.72min, m/z 426[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 12.97(br s,1H)10.16(s,1H)8.46(dd,J＝4.72,1.45Hz,1H)8.11(dd,J＝7.99,1.45Hz,1H)8.02(s,1H)7.74-7.83(m,1H)7.70(s,1H)7.53(dd,J＝7.99,4.72Hz,1H)7.33-7.46(m,1H)6.77(s,1H)3.90(s,3H)2.25(s,3H)。

Example 2:6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.2)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ]-5-methyl-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.219 mL,3.14mmol,2.00 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 1- (3-chloro-2-pyridinyl) -3- (2, 2-trifluoroethoxy) -1H-pyrazole-5-carboxylic acid (prepared as described in Bioorganic and Medicinal Chemistry Letters [ quick report of bioorganic and pharmaceutical chemistry ],2007, vol 17, vol 22, pp 6274-6279) (0.505 g,1.57mmol,1.00 eq.) in acetonitrile (5.0 mL) and pyridine (0.12 mL,1.57mmol,1.0 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (prepared as described in WO 2009/24341 A2) (0.300 g,1.57mmol, 1.00) in acetonitrile (8.7 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.26 mL,3.14mmol,2.00 eq). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was then diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane/ethanol 3:1) to give the desired product 7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time 1.06min, m/z 477[ M+H ] ⁺ ]。

Step 2:6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.280 g,0.587mmol,1.00 eq.) in N, N-dimethylformamide (1.17 mL) was added ammonium acetate (0.136 g,1.76mmol,3 eq.). The reaction mixture was stirred at 50 ℃ for 2 hours. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate/ethanol in cyclohexane 3:1) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.86min, m/z 494[ M+H ] ⁺ ]。

1H NMR (400 MHz, acetone-d) delta ppm 9.74-9.87 (br.s, 1H) 8.48 (dd, J=4.72, 1.45Hz, 1H) 8.06 (dd, J=7.99, 1.45Hz, 1H) 7.93-8.03 (m, 1H) 7.77 (s, 1H) 7.54 (dd, J=7.99, 4.72Hz, 1H) 7.09-7.24 (m, 1H) 6.85 (s, 1H) 4.88 (q, J=8.48 Hz, 2H) 2.35 (s, 3H).

Example 3:6- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.3)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazol-3-yl]-5-methyl-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.719 mL,3.14mmol,2.00 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carboxylic acid (prepared as described in WO 2014/128136 A1) (0.429 g,1.57mmol,1.00 eq.) in acetonitrile (5.0 mL) and pyridine (0.12 mL,1.57mmol,1.0 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (prepared as described in WO 2009/24341,2009, a 2) (0.300 g,1.57mmol, 1.00) in acetonitrile (8.7 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.26 mL,3.14mmol,2.00 eq). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was then diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane/ethanol 3:1) to give the desired product 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time 0.98min, m/z 429[ M+H ] ⁺ ]。

Step 2:6- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.230 g,0.536mmol,1.00 eq.) in N, N-dimethylformamide (1.07 mL) was added ammonium acetate (0.124 g,1.61mmol,3 eq.). The reaction mixture was stirred at 50 ℃ for 2 hours. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate/ethanol in cyclohexane 3:1) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.78min, m/z 446[ M+H ] ⁺ ]。

1H NMR (400 MHz, acetone-d) delta ppm 12.06-12.28 (br s, 1H) 9.81-10.01 (br s, 1H) 8.52 (dd, J=4.72, 1.45Hz, 1H) 8.11 (dd, J=7.99, 1.45Hz, 1H) 8.02 (br s, 1H) 7.78 (s, 1H) 7.61 (dd, J=7.99, 4.72Hz, 1H) 7.56 (s, 1H) 7.09-7.23 (br s, 2H) 7.05 (t, 1H) 2.36 (s, 3H).

Example 4:6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.4)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl]-5-methyl-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.247 mL,3.14mmol,2.00 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxylic acid (prepared as described in Journal of Agricultural and Food Chemistry [ journal of agriculture and food chemistry ], (2012), 60 (31), 7565-7572) (0.458 g,1.57mmol,1.00 eq.) in acetonitrile (5.0 mL) and pyridine (0.12 mL,1.57mmol,1.0 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (prepared as described in WO 2009/24341 A2) (0.300 g,1.57mmol, 1.00) in acetonitrile (8.7 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.26 mL,3.14mmol,2.00 eq). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was then diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time 1.06min, m/z 447[ M+H ] ⁺ ]。

Step 2:6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.051 g,0.114mmol,1.00 eq.) in N, N-dimethylformamide (0.228 mL) was added ammonium acetate (0.0264 g,0.342mmol,3.00 eq.). The reaction mixture was stirred at 50℃for 1 hour. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.85min, m/z 464[ M+H ] ⁺ ]。

1H NMR (400 MHz, acetone-d) delta ppm 11.88-12.32 (br s, 1H) 9.62-10.71 (m, 1H) 8.56 (dd, J=4.72, 1.45Hz, 1H) 8.15 (dd, J=8.17, 1.64Hz, 1H) 8.08 (br s, 1H) 7.80 (s, 1H) 7.73 (s, 1H) 7.66 (dd, J=7.99, 4.72Hz, 1H) 6.96-7.39 (br s, 1H) 2.37 (s, 3H).

Example 5:5- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide (Compound P.7)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl]-5-methyl-1H-triazolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.146 mL, 1.319 mmol,2.00 eq.) in acetonitrile (1.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxylic acid (prepared as described in Journal of Agricultural and Food Chemistry [ journal of agricultural and food chemistry ], (2012), 60 (31), 7565-7572) (0.182 g, 0.264 mmol,1.00 eq.) in acetonitrile (1.0 mL) and pyridine (0.10 mL, 1.219 mmol,2.0 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid (prepared as described in step 1 of example 8) (0.120 g, 0.264 mmol, 1.00) in acetonitrile (3.0 mL) was added to the foregoing solution at room temperature followed by pyridine (0.10 mL,1.249mmol,2.0 eq). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was then diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product 7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one was used as such in the next step.

LC-MS (method 1): retention time 1.00min, m/z 448[ M+H ] ⁺ ]。

Step 2:5- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one (0.290 g,0.647mmol,1.00 eq.) in N, N-dimethylformamide (13 mL) was added ammonium acetate (0.151 g,1.943mmol,3.00 eq.). The reaction mixture was stirred at 50 ℃ overnight. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 5- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl ] amino ] -6-methyl-3H-benzotriazole-4-carboxamide.

LC-MS (method 1): retention time 0.83min, m/z 465[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 15.69-16.03(br s,1H)10.36-10.80(br s,1H)8.45-8.65(m,1H)8.15-8.36(m,1H)7.54-8.06(m,5H)2.23-2.39(s,3H)。

Example 6:5- [ [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide (Compound P.9)

Step 1: 7- [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazol-3-yl]-5-methyl-1H-triazolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.122 mL,1.56mmol,2.00 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carboxylic acid (prepared as described in WO 2009/24341 A2) (0.198 g,0.781mmol,1.00 eq.) in acetonitrile (2.0 mL) and pyridine (0.160 mL,0.78mmol,1.0 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid (prepared as described in step 1 of example 8) (0.150 g,0.781mmol, 1.00) in acetonitrile (4.0 mL) was added to the foregoing solution at 0deg.C, followed by pyridine (0.30 mL,1.56mmol,2.00 eq). The reaction mixture was stirred at 0 ℃ for 30 minutes and then at room temperature for 1 hour. The reaction mixture was then diluted with water and extracted twice with ethyl acetate. The organic layer was washed with water, then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material 7- [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one was used as such in the next step.

LC-MS (method 1): retention time 0.88min, m/z 410[ M+H ] ⁺ ]。

Step 2:5- [ [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one (0.146 g,0.356mmol,1.00 eq.) in ethyl acetate (3.56 mL) was added ammonium acetate (0.083 g,1.07mmol,3 eq.). The reaction mixture was stirred at 60 ℃ for 24 hours. The mixture was quenched by addition of water. The aqueous layer was extracted six times with ethyl acetate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 5- [ [2- (3-chloro-2-pyridinyl) -5-methoxy-pyrazole-3-carbonyl ] amino ] -6-methyl-3H-benzotriazole-4-carboxamide as an off-white solid.

LC-MS (method 1): retention time 0.68min, m/z 427[ M+H ] ⁺ ]。

1H NMR(400MHz,CD ₃ OD)δppm 8.45(dd,J＝4.90,1.64Hz,1H)8.04(dd,J＝7.99,1.45Hz,1H)7.84(s,1H)7.51(dd,J＝7.99,4.72Hz,1H)6.74(s,1H)4.00(s,3H)2.42(d,J＝0.73Hz,3H)。

Example 7:5- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide (Compound P.10)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ]-5-methyl-1H-triazolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.124 mL,1.56mmol,2.00 eq.) in acetonitrile (3.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carboxylic acid (prepared as described in patent CN 105541794A) (0.251 g,0.781mmol,1.00 eq.) in acetonitrile (3.0 mL) and pyridine (0.150 mL,1.858mmol,2.4 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid (prepared as described in step 1 of example 8) (0.150 g,0.781mmol, 1.00) in acetonitrile (3.0 mL) was added to the foregoing solution at 0deg.C, followed by pyridine (0.04 mL,0.495mmol,0.6 eq). The reaction mixture was stirred at 0 ℃ for 30 minutes and then at room temperature for 2 hours. The reaction mixture was then diluted with water and extracted twice with ethyl acetate. The organic layer was washed with water, then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material 7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one was obtained as a brown oil and used as such in the next step.

LC-MS (method 1): retention time 1.25min, m/z 476[ M-H ] ⁺ ]。

Step 2:5- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one (0.387 g, 0.720 mmol,1.00 eq.) in ethyl acetate (12.1 mL) was added ammonium acetate (0.188 g,2.43mmol,3 eq.). The reaction mixture was stirred at 60 ℃ for 24 hours. The mixture was quenched by addition of water. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 5- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl ] amino ] -6-methyl-3H-benzotriazole-4-carboxamide as a yellow oil.

LC-MS (method 1): the retention time was 0.84min, m/z 495[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 15.74-15.94(br s,1H)10.26-10.75(br s,1H)8.48(dd,J＝4.54,1.63Hz,1H)8.13(dd,J＝8.17,1.63Hz,1H)7.89(br s,2H)7.56(dd,J＝8.36,4.72Hz,1H)6.92(s,1H)4.94(d,J＝9.08Hz,2H)2.32(s,3H)。

Example 8:5- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide (Compound P.11)

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Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (di)Fluoromethyl) pyrazol-3-yl]-5-methyl-1H-triazolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.122 mL,1.56mmol,2.00 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carboxylic acid (prepared as described in WO 2014/128136 A1) (0.214 g,0.781mmol,1.00 eq.) in acetonitrile (2.0 mL) and pyridine (0.160 mL,1.96mmol,2.5 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid (prepared as described in step 1 of example 8) (0.150 g,0.781mmol, 1.00) in acetonitrile (4.0 mL) was added to the foregoing solution at 0deg.C, followed by pyridine (0.03 mL,0.367mmol,0.5 eq). The reaction mixture was stirred at 0 ℃ for 30 minutes and then at room temperature for 2 hours. The reaction mixture was then diluted with water and extracted twice with ethyl acetate. The organic layer was washed with water, then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one was used as such in the next step.

LC-MS (method 1): retention time 1.15min, m/z 428[ M-H ] ⁺ ]。

Step 2:5- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one (0.235 g,0.547mmol,1.00 eq.) in ethyl acetate (5.47 mL) was added ammonium acetate (0.127 g,1.64mmol,3 eq.). The reaction mixture was stirred at 60 ℃ for 24 hours. The mixture was quenched by addition of water. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 5- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethyl) pyrazole-3-carbonyl ] amino ] -6-methyl-3H-benzotriazole-4-carboxamide as a yellow oil.

LC-MS (method 1): retention time 0.74min, m/z 447[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 15.14(s,1H)10.58(br s,1H)8.42-8.64(m,1H)8.19(br d,J＝7.99Hz,1H)7.78-7.99(m,3H)7.54-7.70(m,2H)7.07-7.43(m,1H)2.32(br s,3H)。

Example 9:2-benzyl-6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of 5-methyl-indazole-7-carboxamide (Compound P.12)

Step 1:2-benzyl-7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ]-5-methyl-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.113 mL,1.42mmol,2.00 eq.) in acetonitrile (1.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxylic acid (j. Agricutt. Food Chem. [ journal of agriculture and food chemistry ] (2012), 60 (31), 7565-7572) (0.207 g,0.711mmol,1.00 eq.) in acetonitrile (2.0 mL) and pyridine (0.05 mL,0.652mmol,0.92 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 6-amino-2-benzyl-5-methyl-indazole-7-carboxylic acid (0.200 g,0.711mmol, 1.00) in acetonitrile (4.0 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.120 mL, 1.178 mmol,2.08 eq). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture containing the product 2-benzyl-7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -5-methyl-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one was then used directly in the next step without any work-up.

LC-MS (method 1): retention time 1.16min, m/z 537[ M+H ] ⁺ ]。

Step 2:2-benzyl-6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl ]Amino group]Preparation of-5-methyl-indazole-7-carboxamide

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To the foregoing reaction mixture containing 2-benzyl-7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -5-methyl-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.382 g,0.711mmol,1.00 eq.) was added ammonia (2M in ethanol, 3.56ml,7.11mmol,10 eq.). The reaction mixture was stirred at room temperature for 2 hours. Then, additional ammonia (2M in ethanol, 3.56ml,7.11mmol,10 eq.) was added to the reaction mixture. The mixture was stirred at room temperature for 2 hours. Then, the reaction was quenched by addition of water and stirred for 10 minutes. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 2-benzyl-6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl ] amino ] -5-methyl-indazole-7-carboxamide.

LC-MS (method 1): retention time 1.09min, m/z 554[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 11.14(s,1H)8.56(s,1H)8.54(dd,J＝4.54,1.64Hz,1H)8.33(br s,1H)8.22(dd,J＝8.17,1.64Hz,1H)7.82(s,1H)7.80(br s,1H)7.74(d,J＝0.73Hz,1H)7.66(dd,J＝8.36,4.72Hz,1H)7.29-7.38(m,5H)5.69(s,2H)2.16-2.23(s,3H)。

Example 10:2-benzyl-6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl ]Amino group]Preparation of 5-methyl-indazole-7-carboxamide (Compound P.13)

Step 1:2-benzyl-7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl]-5-methyl-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.225 mL,2.84mmol,2.00 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxylic acid (j. Agricutt. Food Chem. [ journal of agriculture and food chemistry ] (2012), 60 (31), 7565-7572) (0.457 g,1.42mmol,1.00 eq.) in acetonitrile (4.0 mL) and pyridine (0.110 mL,0.469mmol,0.95 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 6-amino-2-benzyl-5-methyl-indazole-7-carboxylic acid (0.400 g,0.1.42mmol, 1.00) in acetonitrile (8.0 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.230 mL,2.84mmol,2 equivalents). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture containing the product 2-benzyl-7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ] -5-methyl-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one was then used directly in the next step without any work-up.

LC-MS (method 1): retention time 1.15min, m/z 567[ M+H ] ⁺ ]。

Step 2:2-benzyl-6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-indazole-7-carboxamide

To the foregoing reaction mixture containing 2-benzyl-7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl ] -5-methyl-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.806 g,1.42mmol,1.00 eq.) was added ammonia (2M in ethanol, 7.11ml,14.2mmol,10 eq.). The reaction mixture was stirred at room temperature for 2 hours. Then, additional ammonia (2M in ethanol, 7.11ml,14.2mmol,10 eq.) was added to the reaction mixture. The mixture was stirred at room temperature for 2 hours. Then, the reaction was quenched by addition of water and stirred for 10 minutes. The aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 2-benzyl-6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carbonyl ] amino ] -5-methyl-indazole-7-carboxamide.

LC-MS (method 1): retention time 1.08min, m/z 584[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 11.26(s,1H)8.55(s,1H)8.48(dd,J＝4.72,1.45Hz,1H)8.38-8.43(br.s,1H)8.12(d,J＝8.17Hz,1H)7.83-7.88(br.s,1H)7.74(s,1H)7.56(dd,J＝7.99,4.72Hz,1H)7.29-7.37(m,5H)6.92(s,1H)5.69(s,2H)4.93(q,J＝9.08Hz,2H)2.16-2.22(s,3H)。

Example 11:5-chloro-6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of 1H-indazole-7-carboxamide (Compound P.16)

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Step 1:5-chloro-7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl]-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.0749 mL,0.945mmol,2.00 eq.) in acetonitrile (0.7 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxylic acid (j. Agricutt. Food Chem. [ journal of agriculture and food chemistry ] (2012), 60 (31), 7565-7572) (0.138 g,0.473mmol,1.00 eq.) in acetonitrile (1.2 mL) and pyridine (0.04 mL, 0.4954 mmol,1.04 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 30 minutes. Then, a suspension of 6-amino-5-chloro-1H-indazole-7-carboxylic acid (preparation described in WO 2007/93402 A1) (0.100 g,0.473mmol, 1.00) in acetonitrile (2.8 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.08 mL,0.988mmol,2.09 equivalents). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was then diluted with water and extracted 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 flash chromatography (methanol in dichloromethane) to give the desired product 5-chloro-7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one as a yellow solid.

LC-MS (method 1): retention time 1.06min, m/z 467[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 14.01(s,1H)8.62-8.66(m,1H)8.41-8.44(m,1H)8.36-8.40(m,1H)8.26-8.29(m,1H)7.98-8.01(m,1H)7.77-7.82(m,1H)

19F NMR(377MHz,DMSO-d6)δppm-61.06(s,3F)。

Step 2:5-chloro-6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl]Amino group]Preparation of 1H-indazole-7-carboxamide

To a solution of 5-chloro-7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.050 g,0.11mmol,1.00 eq.) in N, N-dimethylformamide (0.43 mL) was added ammonium acetate (0.025 g,0.32mmol,3.00 eq.). The reaction mixture was stirred at 50℃for 1 hour. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 5-chloro-6- [ [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carbonyl ] amino ] -1H-indazole-7-carboxamide as an off-white solid.

LC-MS (method 1): retention time 0.86min, m/z 484[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 13.37(m,1H)10.64(m,1H)8.54(m,1H)8.22(m,1H)8.13(m,1H)8.05(m,1H)7.86(m,1H)7.80(m,1H)7.58-7.70(m,2H)

19F NMR(377MHz,DMSO-d6)δppm-61.08(s,3F)。

Example 12:6- [ [5- [ (4-chlorophenyl) methoxymethyl ]]-2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.5)

Step 1:5- [ (4-chlorophenyl) methoxymethyl group ]Preparation of-2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylic acid

Sodium hydride (60 mass%, 0.319 g,10.5mmol,3 eq.) was slowly added to a solution of 4-chlorobenzyl alcohol (1.50 g,10.5mmol,3.0 eq.) in tetrahydrofuran (20 mL) under argon at 0deg.C. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, to the reaction mixture was added dropwise a solution of methyl 5- (chloromethyl) -2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylate (prepared as described in patent US2011/152532,2011, a 1) (1.00 g,3.50mmol,1.0 eq.) in tetrahydrofuran (20 mL) at 0 ℃. The solution was warmed to room temperature and stirred for 1 hour. The mixture was then heated to reflux and stirred at that temperature for 2 hours. The reaction mixture was quenched by dropwise addition of saturated aqueous ammonium chloride. The aqueous phase was made acidic (pH 3-4) by the dropwise addition of hydrochloric acid (2N). The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with water, then brine, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylic acid.

LC-MS (method 1): retention time 0.94min, m/z 379[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 13.57(br s,1H)8.54(dd,J＝4.72,1.45Hz,1H)8.21(dd,J＝7.99,1.45Hz,1H)7.65(dd,J＝7.99,4.72Hz,1H)7.32-7.44(m,4H)7.04(s,1H)4.58(s,2H)4.56(s,2H)。

Step 2:7- [5- [ (4-chlorophenyl) methoxymethyl group]-2- (3-chloro-2-pyridinyl) pyrazol-3-yl]-5-methyl-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

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To a solution of methanesulfonyl chloride (0.166 mL,2.09mmol,2.00 eq.) in acetonitrile (1.0 mL) under argon was added dropwise a solution of 5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylic acid (0.390 g,1.05mmol,1.00 eq.) in acetonitrile (4.0 mL) and pyridine (0.085 mL,1.05mmol,1.00 eq.) at 0deg.C. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (preparation described in WO 2009/24341 A2) (0.200 g,1.05mmol,1.00 eq.) in acetonitrile (5.5 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.170 mL,2.10mmol,2.00 eq.). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 7- [5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time 1.14min, m/z 533[ M+H ] ⁺ ]。

Step 3:6- [ [5- [ (4-chlorophenyl) methoxymethyl ]]-2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.170 g,0.319mmol,1.00 eq.) in N, N-dimethylformamide (0.637 mL) was added ammonium acetate (0.074 g,0.956mmol,3 eq.). The reaction mixture was stirred at 50℃for 1 hour. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 6- [ [5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.95min, m/z 551[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 12.97(br s,1H)10.21(s,1H)8.49(dd,J＝4.54,1.64Hz,1H)8.14(dd,J＝7.99,1.45Hz,1H)8.02(s,1H)7.75(br s,1H)7.70(s,1H)7.57(dd,J＝7.99,4.72Hz,1H)7.38-7.47(m,5H)7.33(s,1H)4.65(s,2H)4.62(s,2H)2.24(s,3H)。

Example 13:6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropyloxy) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.6)

Step 1:preparation of methyl 2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropyloxy) pyrazole-3-carboxylate

To a suspension of methyl 2- (3-chloro-2-pyridinyl) -5-oxo-1H-pyrazole-3-carboxylate (prepared as described in patent CN 110615780) (1.00 g,3.94mmol,1 eq.) in acetonitrile (20 mL) was added potassium carbonate (1.12 g,8.08mmol,2.05 eq.) at-5 ℃. The suspension was stirred at 20℃for 15 minutes. Then 2, 3-pentafluoropropyl triflate was added dropwise to the suspension at 5 ℃. The reaction mixture was warmed to room temperature and then heated to reflux overnight. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product methyl 2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazole-3-carboxylate.

LC-MS (method 1): retention time 1.08min, m/z 386[ M+H ] ⁺ ]。

1H NMR (400 MHz, chloroform-d) delta ppm 8.52 (dd, J=4.72, 1.45Hz, 1H) 7.92 (dd, J=8.17, 1.63Hz, 1H) 7.43 (dd, J=8.36, 4.72Hz, 1H) 6.53 (s, 1H) 4.74 (td, J=12.72, 1.09Hz, 2H) 3.79 (s, 3H)

19F NMR (377 MHz, chloroform-d) delta ppm-83.62 (s, CF) ₃ )-123.94(s,CF ₂ )。

Step 2:preparation of 2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazole-3-carboxylic acid

A solution of methyl 2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazole-3-carboxylate (1.647 g,4.270mmol,1 eq.) and lithium hydroxide monohydrate (1.075 g,25.62mmol,6 eq.) in 2-methyltetrahydrofuran (10.68 mL) and water (10.68 mL) was stirred at room temperature for 3 hours. 2-methyltetrahydrofuran was evaporated from the reaction mixture under reduced pressure. To the resulting aqueous mixture was added ethyl acetate, followed by hydrochloric acid (aqueous solution, 1N). The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, then brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give the desired compound 2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropyloxy) pyrazole-3-carboxylic acid as a white powder.

LC-MS (method 1): retention time 0.93min, m/z 372[ M+H ] ⁺ ]。

1H NMR (400 MHz, solvent) delta ppm 8.51 (dd, J=4.72, 1.45Hz, 1H) 8.17 (dd, J=7.99, 1.45Hz, 1H) 7.61 (dd, J=7.99, 4.72Hz, 1H) 6.59 (br s, 1H) 4.96 (br t, J=13.26 Hz, 2H).

Step 3:7- [2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazol-3-yl]-5-methyl-1H-pyrazolo [3,4-f ][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.166 mL,2.09mmol,2.00 eq.) in acetonitrile (1.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropyloxy) pyrazole-3-carboxylic acid (0.396 g,1.05mmol,1.00 eq.) in acetonitrile (4.0 mL) and pyridine (0.085 mL,1.05mmol,1.00 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (preparation described in WO 2009/24341 A2) (0.200 g,1.05mmol,1.00 eq.) in acetonitrile (5.5 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.170 mL,2.10mmol,2.00 eq.). The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was diluted with ethyl acetate, washed twice with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 7- [2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time 1.13min, m/z 527[ M+H ] ⁺ ]。

Step 4:6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropyloxy) pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.140 g,0.266mmol,1.00 eq.) in N, N-dimethylformamide (0.532 mL) was added ammonium acetate (0.062 g,0.797mmol,3 eq.). The reaction mixture was stirred at 50℃for 1 hour. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (methanol in dichloromethane) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5- (2, 3-pentafluoropropoxy) pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.94min, m/z 544[ M+H ] ⁺ ]。

1H NMR (400 MHz, acetone-d 6) delta ppm 12.23 (br s, 1H) 10.17 (br s, 1H) 8.47 (dd, J=4.72, 1.82Hz, 1H) 8.05 (dd, J=7.99, 1.45Hz, 1H) 8.03 (s, 1H) 7.68 (s, 1H) 7.52 (dd, J=7.99, 4.72Hz, 1H) 6.89 (s, 1H) 4.92-5.03 (m, 2H) 2.29 (s, 3H).

Example 14:5- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide (Compound P.8)

Step 1:preparation of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid

To a suspension of 5-methyl-1, 6-dihydropyrrolo [3,2-e ] benzotriazole-7, 8-dione (prepared as described in bioorg. Med. Chem. [ bioorganic and pharmaceutical chemistry ],2016,24 (3), 403-427) (0.150 g,0.742mmol,1.00 eq.) in water (1.56 mL) was added sodium hydroxide (0.033 g, 0.812 mmol,1.10 eq.) followed by sodium chloride (0.092 g,1.56mmol,2.10 eq.). The mixture was stirred at room temperature for 45 minutes. The brown solution was cooled to 0 ℃ and hydrogen peroxide (30 mass%, 0.189ml,1.85mmol,2.50 eq.) was slowly added. The reaction was stirred at 0 ℃ for 20 minutes and then at room temperature for 1 hour 30 minutes. Acetic acid was added to the reaction until the pH reached pH 3-4. Precipitation occurs. It was filtered and dried under reduced pressure. The solid was dissolved in ethyl acetate, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the desired crude product 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid as an orange solid.

LC-MS (method 1): the retention time was 0.33min, m/z 193[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 14.54-14.73(s,1H)7.73-7.89(s,1H)1.90-1.93(s,3H)。

Step 2:7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazol-3-yl]-5-methyl-1H-triazolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.182 mL,1.56mmol,2.0 eq.) in acetonitrile (3.0 mL) was added dropwise 2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carboxylic acid (e.g., bioorg. Med. Chem. Lett.) under argon at 0deg.C],2007,17 (22), 6274-6279) (0.228 g,0.788mmol,1.0 eq.) in acetonitrile (3.0 mL) and pyridine (0.150 mL,1.95mmol,2.5 eq.). The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid (0.15 g,0.780mmol,1.0 eq.) in acetonitrile (3.0 mL) was added to the solution at room temperature followed by pyridine (0.04 mL,0.495mmol,0.5 eq.). The reaction mixture was stirred at room temperature for 2 hours. Pouring the reaction mixture into saturated aqueous NaHCO ₃ Is a kind of medium. The aqueous layer was 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 yellow oil was used without further purification in the following step.

LC-MS (method 1): retention time 1.18min, m/z 444[ M-H ] ⁺ ]。

Step 3:5- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide

To a suspension of 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazol-3-yl ] -5-methyl-1H-triazolo [4,5-f ] [3,1] benzoxazin-9-one (0.348 g,0.767mmol,1.00 eq.) in ethyl acetate (7.67 mL) was added ammonium acetate (0.178 g,2.30mmol,3 eq.). The reaction mixture was stirred at 60 ℃ overnight. The mixture was quenched by addition of water and extracted with ethyl acetate. The aqueous layer was extracted 3 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 flash chromatography (ethyl acetate in cyclohexane) to give the desired product 5- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carbonyl ] amino ] -6-methyl-3H-benzotriazole-4-carboxamide as a yellow solid.

LC-MS (method 1): retention time 0.77min, m/z 463[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 15.84(br s,1H)10.54(br s,1H)8.49(dd,J＝4.72,1.45Hz,1H)8.15(dd,J＝7.99,1.45Hz,1H)7.87(br s,1H)7.58(dd,J＝8.36,4.72Hz,1H)7.43(t,1H)7.10(s,1H)2.31(s,3H)

Example 15:6- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.14)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazol-3-yl]-5-methyl-1H-pyrazolo [3,4-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.166 mL,2.09mmol,2.0 eq.) in acetonitrile (2.0 mL) under argon was added dropwise a solution of 2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carboxylic acid (prepared as described in bioorg. Med. Chem. Lett. [ bioorganic & pharmaceutical chemistry rapid, 2007,17 (22), 6274-6279) (0.303 g,1.05mmol,1.0 eq.) in acetonitrile (4.0 mL) and pyridine (0.080 mL,0.989mmol,1.0 eq.) under argon. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (prepared as described in WO 2009/24341) (0.200 g,1.05mmol,1.0 eq.) in acetonitrile (4.5 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.170 mL,2.10mmol,2.0 eq.). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, washed twice with water, then brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate/ethanol in cyclohexane (3:1)) to give the desired product 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one.

LC-MS (method 1): retention time0.99min,m/z 445[M-H ⁺ ]。

Step 2:6- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carbonyl]Amino group]Preparation of (E) -5-methyl-1H-indazole-7-carboxamide

To a solution of 7- [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one (0.245 g, 0.553mmol, 1.00 eq.) in N, N-dimethylformamide (1.10 mL) was added ammonium acetate (0.127 g,1.65mmol,3 eq.). The reaction mixture was stirred at 50 ℃ for 6 hours. The mixture was quenched by addition of water. The reaction mixture was diluted with ethyl acetate, washed twice with water, then once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5- (difluoromethoxy) pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide.

LC-MS (method 1): retention time 0.80min, m/z 462[ M+H ] ⁺ ]。

1H NMR (400 MHz, acetone-d 6) delta ppm 11.93-12.42 (m, 1H) 9.71-10.21 (m, 1H) 8.49 (dd, J=4.72, 1.82Hz, 1H) 8.08 (dd, J=7.99, 1.45Hz, 1H) 7.78 (s, 1H) 7.57 (dd, J=7.99, 4.72Hz, 1H) 7.11-7.49 (t, 1H) 7.02 (s, 1H) 2.40 (d, J=0.73 Hz, 1H) 2.35 (s, 3H).

Example 16:5- [ [5- [ (4-chlorophenyl) methoxymethyl ]]-2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide (Compound P.15)

Step 1:7- [5- [ (4-chlorophenyl) methoxymethyl group]-2- (3-chloro-2-pyridinyl) pyrazol-3-yl]-5-methyl-3H-triazolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a solution of methanesulfonyl chloride (0.0148 mL,0.187mmol,2.00 eq.) in acetonitrile (0.2 mL) under argon was added dropwise 5- [ (4-chlorophenyl) methoxymethyl group at 0deg.C]A solution of 2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylic acid (prepared as described above) (0.035 g,0.093mmol,1.00 eq.) in acetonitrile (0.6 mL) and pyridine (0.01 mL,0.140mmol,1.50 eq.). The reaction mixture was stirred at 0 ℃ for 30 minutes and at room temperature for 2 hours. Then, a suspension of 5-amino-6-methyl-3H-benzotriazole-4-carboxylic acid (preparation described above) (0.018 g,0.093mmol, 1.00) in acetonitrile (0.6 mL) was added to the foregoing solution at room temperature, followed by pyridine (0.01 mL,0.140mmol,1.50 eq). The reaction mixture was stirred at room temperature for 20 hours. Methanesulfonyl chloride (0.002ml, 0.028mmol,0.30 eq.) was added to the brown suspension. The mixture was stirred at room temperature for 1 hour. It was then diluted with ethyl acetate and NaHCO was added ₃ Saturated aqueous solution. The organic layer was washed 5 times with water, once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 7- [5- [ (4-chlorophenyl) methoxymethyl as an orange solid]-2- (3-chloro-2-pyridinyl) pyrazol-3-yl]-5-methyl-3H-triazolo [4,5-f][3,1]Benzoxazin-9-ones.

LC-MS (method 1): retention time 1.08min, m/z 534[ M+H ] ⁺ ]。

Step 2:5- [ [5- [ (4-chlorophenyl) methoxymethyl ]]-2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl]Amino group]Preparation of-6-methyl-3H-benzotriazole-4-carboxamide

To a solution of 7- [5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazol-3-yl ] -5-methyl-3H-triazolo [4,5-f ] [3,1] benzoxazin-9-one (0.025 g,0.048mmol,1.00 eq.) in acetonitrile (0.954 mL) was added ammonia (2M in ethanol, 0.477mL,0.954mmol,20 eq.). The reaction mixture was stirred at room temperature for 22 hours. The mixture was quenched by addition of water. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with water, then brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography (ethyl acetate in cyclohexane) to give the desired product 5- [ [5- [ (4-chlorophenyl) methoxymethyl ] -2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl ] amino ] -6-methyl-3H-benzotriazole-4-carboxamide as an off-white solid.

LC-MS (method 1): retention time 0.92min, m/z 551[ M+H ] ⁺ ]。

1H NMR (400 MHz, chloroform-d) delta ppm 11.78-12.01 (m, 1H) 9.40 (br s, 1H) 8.49 (dd, J=4.72, 1.82Hz, 1H) 7.86 (dd, J=7.99, 1.82Hz, 1H) 7.53 (s, 1H) 7.32-7.39 (m, 5H) 7.24 (s, 1H) 4.74 (s, 2H) 4.62 (s, 2H) 2.39 (s, 3H).

Example 17:6- [ [2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl ]]Methyl group]Pyrazole-3-carbonyl]Amino group]Preparation of-5-methyl-1H-indazole-7-carboxamide (Compound P.18)

To a solution of methanesulfonyl chloride (0.450 mL,5.68mmol,2.00 eq.) in acetonitrile (28 mL) under argon, a solution of 2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl ] methyl ] pyrazole-3-carboxylic acid (prepared as described in US 2014/235865 A1) (1.06 g,2.84mmol,1.00 eq.) in acetonitrile (28 mL) and pyridine (0.46 mL,5.68mmol,2.00 eq.) was added dropwise. The reaction mixture was stirred at 0 ℃ for 30 minutes. Then, a suspension of 6-amino-5-methyl-1H-indazole-7-carboxylic acid (prepared as described in WO 2009/24341 A2) (1.00 g,2.84mmol,1.00 eq.) in acetonitrile (28 mL) was added to the aforementioned solution at room temperature, followed by pyridine (0.23 mL,2.84mmol,1.00 eq.). The desired intermediate 7- [2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl ] methyl ] pyrazol-3-yl ] -5-methyl-1H-pyrazolo [3,4-f ] [3,1] benzoxazin-9-one is formed.

To this reaction mixture was added ammonia (7M in methanol, 8.1ml,56.8mmol,20 eq). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with ethyl acetate and washed with water, then brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. After the crude material was first purified by flash chromatography, it was purified by reverse phase chromatography (ethyl acetate/ethanol in cyclohexane) to give the desired product 6- [ [2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl ] methyl ] pyrazole-3-carbonyl ] amino ] -5-methyl-1H-indazole-7-carboxamide as a beige solid.

LC-MS (method 1): retention time 0.88min, m/z 546[ M+H ] ⁺ ]。

1H NMR(400MHz,DMSO-d6)δppm 12.99(s,1H)10.28(s,1H)8.48(dd,J＝4.6,1.4Hz,1H)8.15(dd,J＝8.0,1.3Hz,1H)8.01(d,J＝0.9Hz,1H)7.72(br s,1H)7.68(s,1H)7.59(dd,J＝8.0,4.7Hz,1H)7.42(br s,1H)7.39-7.40(m,1H)6.33(s,2H)2.22(s,3H)。

Example 18: preparation of N- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxamide

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl]-2, 2-difluoro-5-methyl- [1,3]Dioxolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

This compound was prepared from 5-amino-2, 2-difluoro-6-methyl-1, 3-benzodioxole-4-carboxylic acid (CAS accession number 1103246-40-7, described in WO 2009010260) and 2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxylic acid (prepared as described in Journal of Agricultural and Food Chemistry [ journal of agricultural and food chemistry ], (2012), 60 (31), 7565-7572) as in step 1 of example 11.

The crude 7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -2, 2-difluoro-5-methyl- [1,3] dioxolo [4,5-f ] [3,1] benzoxazin-9-one was used as such in the next step.

LC-MS (method 1): retention time 1.21min, m/z 487[ M+H ] ⁺ ]。

Step 2:preparation of N- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazole-3-carboxamide

To a suspension of 7- [2- (3-chloro-2-pyridinyl) -5- (trifluoromethyl) pyrazol-3-yl ] -2, 2-difluoro-5-methyl- [1,3] dioxolo [4,5-f ] [3,1] benzoxazin-9-one (0.300 g,0.616mmol,1.00 eq.) in acetonitrile (12 mL) was added ammonia (2M in ethanol, 3.08mL,6.16mmol,10.0 eq.) under argon at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The reaction mixture was purified by flash chromatography (ethyl acetate in cyclohexane) to give the title compound as a yellow solid.

LC-MS (method 1): retention time 0.98min, m/z 504[ M+H ] ] ⁺ 。

1H NMR(400MHz,CD3OD)δppm 8.52(dd,J＝4.72,1.45Hz,1H),8.12(dd,J＝8.36,1.45Hz,1H),7.58-7.63(m,2H),7.20(s,1H),2.25(s,3H)。

Example 19:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl ]]Methyl group]Pyrazol-3-yl]-2, 2-difluoro-5-methyl- [1,3]Dioxolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 5-amino-2, 2-difluoro-6-methyl-1, 3-benzodioxole-4-carboxylic acid ((CAS RN 1103246-40-7, described in WO 2009010260)) in acetonitrile (10.0 mL) (200 mg,0.865 mmol), 2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl) was added thereto]Methyl group]Pyrazole-3-carboxylic acid ((CAS No. 1352319-02-8, prepared as described in WO 2019224678)) (323 mg,0.865 mmol), pyridine (0.210 mL,2.60 mmol) and methanesulfonyl chloride (0.268 mL,3.46 mmol) was added at 0deg.C. The resulting reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was analyzed by TLC (30% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2X 100 mL). The combined organic layers were washed with brine (50, 0 mL), and dried over Na ₂ SO ₄ Drying and concentration under reduced pressure gave the crude title compound as a yellow solid which was used in the next step without purification. MS: m/z=568.8 [ m+h ]] ⁺ 。

Step 2:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 7- [2- (3-chloro-2-pyridinyl) -5- [ [5- (trifluoromethyl) tetrazol-2-yl ] methyl ] pyrazol-3-yl ] -2, 2-difluoro-5-methyl- [1,3] dioxolo [4,5-f ] [3,1] benzoxazin-9-one (preparation described above) (200 mg,0.352 mmol) in acetonitrile (10.0 mL) was added thereto and 2M ammonia in ethanol (3.0 mL) was added at room temperature. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure to give a crude mixture. The crude mixture was purified by combi flash (0% to 100% water/acetonitrile). The pure fractions were combined and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ10.24(s,1H),8.47(dd,J＝4.8Hz,1.6Hz,1H),8.13(dd,J＝8.0Hz,1.6Hz,1H),7.78(s,1H),7.73(s,1H),7.64-7.56(m,1H),7.40(s,1H),7.35(s,1H),6.31(s,2H),2.13(s,3H)；MS:m/z＝586.0[M+H] ⁺ 。

Melting point: 135-140 DEG C

Example 20:preparation of N- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carboxamide (Compound P.25)

Step 1:7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl]-2, 2-difluoro-5-methyl- [1,3]Dioxolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

The preparation of the title compound was performed in analogy to step 1 of compound p.24 using 2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carboxylic acid (CAS RN 500011-97-2, bioorg.med.chem.lett. [ bio-organic and pharmaceutical chemistry rapid ] (2007), 17 (22), 6274-6279).

The crude title compound was isolated as a pale yellow solid and used in the next step without purification.

MS:m/z＝516.8[M+H] ⁺ 。

Step 2:preparation of N- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazole-3-carboxamide

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon and 7- [2- (3-chloro-2-pyridinyl) -5- (2, 2-trifluoroethoxy) pyrazol-3-yl in acetonitrile (10.0 mL) was added thereto ]-2, 2-difluoro-5-methyl- [1,3]Dioxolo [4,5-f][3,1]Benzoxazin-9-one (preparation described above) (140 mg, 0.271mmol) and ammonia (2 mol/L,1.35mL,2.71 mmol) was added at 0deg.C. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (40% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2X 100 mL). The combined organic layers were washed with brine (50.0 mL), and dried over Na ₂ SO ₄ Dried and concentrated under reduced pressure to give a crude mixture. The crude reaction mixture was purified by reversed phase combi flash column chromatography (combiflash, 0% to 100% hexanes/EtOAC). The pure fractions were combined and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ ¹ H NMR(DMSO-d _6, 400MHz):δ10.18(s,1H),8.47(dd,J＝1.6Hz,4.8Hz,1H),8.12(dd,J＝1.6Hz,8.0Hz,1H),7.80(d,J＝7.2Hz,2H),7.56(dd,J＝4.4Hz,8.0Hz,1H),7.42(s,1H),6.83(s,1H),4.95(q,J＝4.8Hz,9.2Hz,2H),2.15(s,3H)。MS:m/z＝534.0[M+H] ⁺ 。

Melting point: 240-245 DEG C

Example 21:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide (Compound P.21)

Step 1:2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl]Methyl group]Pyrazole-3-carboxylic acid ethyl ester and 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl ] ]Methyl group]Preparation of pyrazole-3-carboxylic acid ethyl ester

To a 50mL, two-necked round bottom flask equipped with a nitrogen balloon, charged with ethyl 5- (bromomethyl) -2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylate (prepared in a similar manner as described in WO 2019/224678) (1.50 g,4.35 mmol) in acetonitrile (60.0 mL) was added 4- (trifluoromethyl) -1H-triazole (0.716 g,5.22 mmol) and dipotassium carbonate (1.80 g,13.1 mmol) at room temperature. The resulting reaction mixture was stirred at 80℃for 3 hours. The reaction mixture was analyzed by TLC (30% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (10.0 mL) and extracted with EtOAc (3X 50.0 mL). The combined organic layers were washed with brine (20.0 mL), and dried over Na ₂ SO ₄ Dried and concentrated under reduced pressure to give a crude mixture. The crude mixture was purified by flash column chromatography (combiflash, 0% to 100% EtOAc/hexanes). The pure fractions were combined and evaporated under reduced pressure to give 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl) as an off-white solid]Methyl group]Pyrazole-3-carboxylic acid ethyl ester and 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl ] as off-white solid]Methyl group]Pyrazole-3-carboxylic acid ethyl ester.

2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl ] methyl ] pyrazole-3-carboxylic acid ethyl ester:

¹ H NMR(400MHz,DMSO-d ₆ ):δ8.55(dd,J＝4.8Hz,1.6Hz,1H),8.49(s,1H),8.26(dd,J＝8.0Hz,1.2Hz,1H),7.71-7.68(m,1H),7.13(s,1H),5.93(s,2H),4.14(q,J＝6.8Hz,2H),1.08(t,J＝6.8Hz,3H)；MS:m/z＝400.9[M+H] ⁺ 。

2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl ] methyl ] pyrazole-3-carboxylic acid ethyl ester:

¹ H NMR(DMSO-d _6, 400MHz):δ9.05(d,J＝0.8Hz,1H),8.56(dd,J＝1.2Hz,4.4Hz,1H),8.27(dd,J＝1.6Hz,8.0Hz,1H),7.71(dd,J＝4.8Hz,8.0Hz,1H),7.23(s,1H),5.85(s,2H),4.17(q,J＝7.2Hz,8.8Hz,2H),1.10(t,J＝6.8Hz,3H)；MS:m/z＝400.9[M+H] ⁺ 。

step 2:2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxylic acid

A50 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl ] in methanol (10.0 mL) was added thereto]Methyl group]Pyrazole-3-carboxylic acid ethyl ester (preparation described above) (500 mg,1.25 mmol). Tetrahydrofuran (5.00 mL) was added dropwise, and lithium hydroxide hydrate (262 mg,6.24 mmol) and water (3.0 mL) were added to the reaction mixture at 0deg.C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure and the pH was adjusted to 2.0 to 3.0 with 2N HCl at 0 ℃. The reaction mass was extracted with 10% MeOH/DCM (4X 50.0 mL). The combined organic layers were washed with brine (10.0 mL), and dried over Na ₂ SO ₄ Dried and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(DMSO-d _6, 400MHz):δ13.75-13.61(brs,1H),8.37(dd,J＝1.2Hz,4.8Hz,1H),8.48(s,1H),8.22(dd,J＝1.2Hz,8.0Hz,1H),7.66(dd,J＝0.8Hz,1.2Hz,1H),6.99(s,1H),5.89(s,2H)。

MS:m/z＝372.9[M+H] ⁺ 。

Step 3:7- [2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl ]]Methyl group]Pyrazol-3-yl]-2, 2-difluoro-5-methyl- [1,3 ]Dioxolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 5-amino-2, 2-difluoro-6-methyl-1, 3-benzodioxole-4-carboxylic acid (200 mg,0.865 mmol) in acetonitrile (10.0 mL) was added thereto. 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl ] is added at 0deg.C]Methyl group]Pyrazole-3-carboxylic acid (preparation as described above) (387 mg,1.04 mmol), pyridine (0.210 mL,2.60 mmol)And methanesulfonyl chloride (0.268 mL,3.46 mmol). The resulting reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was analyzed by TLC (30% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2X 100 mL). The combined organic layers were washed with brine (50.0 mL), and dried over Na ₂ SO ₄ Dried and concentrated under reduced pressure to give the title compound as a yellow solid. This compound was used as such in the following steps.

MS:m/z＝567.9[M+H] ⁺ 。

Step 4:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 7- [2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) tetrazol-2-yl ] methyl ] pyrazol-3-yl ] -2, 2-difluoro-5-methyl- [1,3] dioxolo [4,5-f ] [3,1] benzoxazin-9-one (preparation described above) (200 mg,0.352 mmol) in acetonitrile (10.0 mL) was added thereto and ammonia (2M in ethanol) (3.0 mL) was added at room temperature. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure to obtain a crude mixture. The crude mixture obtained was purified by combi flash (0% to 100% acetonitrile/water). The pure fractions were combined and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(DMSO-d _6, 400MHz):δ10.22(s,1H),8.55(s,1H),8.48(dd,J＝1.6Hz,4.8Hz,1H),8.15(dd,J＝1.6Hz,8.0Hz,1H),7.79(s,1H),7.74(s,1H),7.59(dd,J＝4.8Hz,8.4Hz,1H),7.40(s,1H),7.24(s,1H),5.95(s,2H),2.12(s,3H)；MS:m/z＝585.0[M+H] ⁺ 。

Melting point: 165-170 ℃.

Example 22:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide (Compound P.22)

Step 1:2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl)]Methyl group]Preparation of pyrazole-3-carboxylic acid

A50 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl ] in methanol (10.0 mL) was added thereto]Methyl group]Pyrazole-3-carboxylic acid ethyl ester (preparation described in step 1 of preparation example 21) (650 mg,1.62 mmol). Tetrahydrofuran (5.00 mL) was added dropwise, and lithium hydroxide hydrate (340 mg,8.11 mmol) and water (3.0 mL) were added to the reaction mixture at 0deg.C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure and the pH was adjusted to 2.0 to 3.0 with 2N HCl at 0 ℃. The reaction mass was extracted with ethyl acetate (3X 20 mL). The combined organic layers were washed with brine (10.0 mL), and dried over Na ₂ SO ₄ Dried and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ13.7(s,1H),9.02(d,J＝0.8Hz,1H),8.54(dd,J＝4.8Hz,1.6Hz,1H),8.22(dd,J＝8.0Hz,1.6Hz,1H),7.67-7.64(m,1H),7.12(s,1H),5.83(s,2H)。

MS:m/z＝372.9[M+H] ⁺ 。

I delete the part of the Curia protocol still hanging there-!

Step 2:7- [2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl)]Methyl group]Pyrazol-3-yl]-2, 2-difluoro-5-methyl- [1,3]Dioxolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon and 5-amino-2, 2-difluoro-6-methyl-1, 3-benzodioxole-4-carboxylic acid (200 mg,0.865 mmol), 2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl) in acetonitrile (10.0 mL) was added thereto]Methyl group]Pyrazole-3-carboxylic acid (preparation described above) (387 mg,1.04 mmol), pyridine (0.210 mL,2.60 mmol) and methanesulfonyl chloride (0.268 mL,3.46 mmol) was added at 0deg.C. The resulting reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was analyzed by TLC (30% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2X 100 mL). The combined organic layers were washed with brine (50.0 mL), and dried over Na ₂ SO ₄ Dried and concentrated under reduced pressure to give the crude title compound as a yellow solid. The compound was used in the following step without further purification.

MS:m/z＝567.8[M+H] ⁺ 。

Step 3:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl ]Methyl group]Preparation of pyrazole-3-carboxamide

To a 25mL two-necked round bottom flask equipped with a nitrogen balloon was added 7- [2- (3-chloro-2-pyridinyl) -5- [ [4- (trifluoromethyl) triazol-1-yl ] methyl ] pyrazol-3-yl ] -2, 2-difluoro-5-methyl- [1,3] dioxolo [4,5-f ] [3,1] benzoxazin-9-one (200 mg,0.352 mmol) in acetonitrile (10.0 mL) and ammonia (2M in ethanol) (3.0 mL) was added at room temperature. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure to give a crude mixture, which was purified by combiflash reverse phase column chromatography (combiflash, 0% to 100% acetonitrile/water). The pure fractions were combined and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ10.12(brs,1H),9.08(d,J＝0.8Hz,1H),8.47(dd,J＝4.8Hz,1.6Hz,1H),8.12(dd,J＝8.0Hz,1.6Hz,1H),7.80(s,1H),7.73(s,1H),7.59-7.56(m,1H),7.40(s,1H),7.23(s,1H),5.88(s,2H),2.12(s,3H)；

MS:m/z＝585.0[M+H] ⁺ 。

Melting point: 210-220 ℃.

Example 23:n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [5- [4- (trifluoromethyl) phenyl ]]Tetrazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide (Compound P.23)

Step 1:2- (3-chloro-2-pyridinyl) -5- [ [5- [4- (trifluoromethyl) phenyl ]]Tetrazol-2-yl ]Methyl group]Preparation of pyrazole-3-carboxylic acid

To a 25mL two-necked round bottom flask was added 2- (3-chloro-2-pyridinyl) -5- [ [5- [4- (trifluoromethyl) phenyl ] in methanol (10.0 mL)]Tetrazol-2-yl]Methyl group]Pyrazole-3-carboxylic acid ethyl ester (prepared in analogy to the method described in WO 2019/224678) (600 mg,1.24 mmol) and lithium hydroxide hydrate (428 mg,10.2 mmol) and water (3.00 ml,0 mmol) were added at 0 ℃ and stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. Most of the solvent was evaporated under reduced pressure and the pH was adjusted to 2.0 to 3.0 with 2N HCl at 0 ℃. The reaction mass was extracted with ethyl acetate (3X 20 mL). The combined organic layers were washed with brine (10.0 mL), and dried over Na ₂ SO ₄ Dried and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ8.47(dd,J＝4.4Hz,1.2Hz,1H),8.29(d,J＝8.0Hz,2H),8.14(dd,J＝8.4Hz,1.6Hz,1H),7.93(d,J＝8.4Hz,2H),7.60-7.57(m,1H),6.89(s,1H),6.10(s,2H)；MS:m/z＝449.8[M+H] ⁺ 。

Step 2:chloro-2-pyridinyl) -5- [ [5- [4- (trifluoromethyl) phenyl ]]Tetrazol-2-yl]Methyl group]Pyrazol-3-yl]-2, 2-difluoro-5-methyl- [1,3]Dioxolo [4,5-f][3,1]Preparation of benzoxazin-9-ones

To a 25mL two-necked round bottom flask equipped with a nitrogen balloon was added 5-amino-2, 2-difluoro-6-methyl-1, 3-benzodioxole-4-carboxylic acid (160 mg,0.692 mmol) in acetonitrile (10.0 mL). 1- (3-chloro-2-pyridinyl) -4- [ [5- [4- (trifluoromethyl) phenyl ] at 0deg.C ]Tetrazol-2-yl]Methyl group]Pyrrole-2-carboxylic acid (preparation described above) (311 mg,0.692 mmol), pyridine (0.168 mL,2.08 mmol) and methanesulfonyl chloride (0.214 mL,2.77 mmol). The resulting reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was analyzed by TLC (30% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2X 100 mL). The combined organic layers were washed with brine (50.0 mL), and dried over Na ₂ SO ₄ Dried and concentrated under reduced pressure to give the crude title compound as a yellow solid. The compound was used as such in the following step.

MS:m/z＝644.8[M+H] ⁺ 。

Step 3: n- (4-carbamoyl-2, 2-difluoro-6-methyl-1, 3-benzodioxol-5-yl) -2- (3-chloro-2-pyridinyl) -5- [ [5- [4- (trifluoromethyl) phenyl ]]Tetrazol-2-yl]Methyl group]Preparation of pyrazole-3-carboxamide (Compound 23)

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 7- [2- (3-chloro-2-pyridinyl) -5- [ [5- [4- (trifluoromethyl) phenyl ] tetrazol-2-yl ] methyl ] pyrazol-3-yl ] -2, 2-difluoro-5-methyl- [1,3] dioxolo [4,5-f ] [3,1] benzoxazin-9-one (preparation described above) (200 mg,0.310 mmol) in acetonitrile (10.0 mL) was added thereto. Ammonia (2M in ethanol) (4.0 mL) was added at room temperature. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure to give a crude mixture which was purified by flash column chromatography (combiflash, 0% to 100% EtOAc/hexanes). The pure fractions were combined and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ10.22(s,1H),8.48-8.46(m,1H),8.32(d,J＝8.0Hz,2H),8.14(d,J＝8.4Hz,1H),7.96(d,J＝8.0Hz,2H),7.80(s,1H),7.73(s,1H),7.59-7.56(m,1H),7.40(s,1H),7.30(s,1H),6.23(s,2H),2.11(s,3H)；MS:m/z＝661.8[M+H] ⁺ 。

Melting point: 125-130 ℃.

Example 24:6- [ [ 5-bromo-2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl]Amino group]Preparation of-2, 5-dimethyl-1, 3-benzoxazole-7-carboxamide (Compound P.20)

Step 1:preparation of 7-bromo-2, 5-dimethyl-1, 3-benzoxazol-6-amine

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and 2, 5-dimethyl-1, 3-benzooxazol-6-amine (CAS RN 88172-90-1, commercially available) (0.900 g,5.55 mmol) in acetonitrile (30.0 mL) was added thereto. 1-bromopyrrolidine-2, 5-dione (0.988 g,5.55 mmol) was added to the reaction mixture at 0℃and stirred at room temperature for 1 hour. The reaction mixture was analyzed by TLC (20% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (50.0 mL) and extracted with EtOAc (3X 50.0 mL). The combined organic layers were washed with brine (30.0 mL), water (30.0 mL), and dried over Na ₂ SO ₄ The drying is carried out,and concentrated under reduced pressure to give a crude residue, which was purified by flash chromatography (Combiflash). The pure fractions were combined and evaporated under reduced pressure to give the title compound as a brown solid.

¹ H NMR(CDCl ₃ ,400MHz):δ7.26(d,J＝1.2Hz,1H),4.11(s,2H),2.60(s,3H),2.29(d,J＝0.8Hz,3H)。

Step 2:preparation of methyl 6-amino-2, 5-dimethyl-1, 3-benzoxazole-7-carboxylate

To a 100mL autoclave vessel was added 7-bromo-2, 5-dimethyl-1, 3-benzoxazol-6-amine (preparation described above) (900 mg,3.73 mmol), N-diethylamine (1.57 mL,11.2 mmol) and 1,1' -bis (diphenylphosphino) ferrocene-palladium (II) dichloride dichloromethane complex (305 mg,0.373 mmol) in methanol (30.0 mL) and stirred at 100℃under carbon monoxide (100 psi) for 12 hours. The reaction mixture was analyzed by TLC (30% EtOAc/hexanes) and indicated no starting material. The reaction mixture was filtered through celite. The filtrate was evaporated to give a crude residue which was purified by combi flash chromatography (30% ethyl acetate/hexane). The pure fractions were combined and evaporated under reduced pressure to give the title compound as a pale brown solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ7.46(s,1H),6.01(s,2H),3.99(s,3H),2.60(s,3H),2.23(s,3H)。

Step 3:preparation of 6-amino-2, 5-dimethyl-1, 3-benzoxazole-7-carboxylic acid

A25 mL two-necked round bottom flask was equipped with a nitrogen balloon, and methyl 6-amino-2, 5-dimethyl-1, 3-benzoxazole-7-carboxylate (preparation described above) (600 mg,2.72 mmol) in methanol (10.0 mL) was added thereto. Mixing the mixture into the reaction at 0 DEG CTetrahydrofuran (10.0 mL), lithium hydroxide hydrate (578mg, 13.6 mmol) and water (5.0 mL) were added to the mixture, and stirred at room temperature for 12 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. Most of the solvent was evaporated under reduced pressure and the pH was adjusted to 2.0 to 3.0 with 2N HCl at 0 ℃. The reaction mass was extracted with 10% MeOH/DCM (4X 50 mL). The combined organic layers were washed with brine (10.0 mL), and dried over Na ₂ SO ₄ Dried and evaporated under reduced pressure to give the title compound as a brown solid.

MS:m/z＝207.1[M+H] ⁺ 。

Step 4:7- [ 5-bromo-2- (3-chloro-2-pyridinyl) pyrazol-3-yl]-2, 5-dimethyl-oxazolo [5,4-f][3,1]Preparation of benzoxazin-9-ones

To a stirred solution of 6-amino-2, 5-dimethyl-1, 3-benzoxazole-7-carboxylic acid (prepared as described above) (250 mg,1.21 mmol) in acetonitrile (5.0 mL) was added 5-bromo-2- (3-chloro-2-pyridinyl) pyrazole-3-carboxylic acid (440 mg,1.45 mmol), pyridine (0.254 mL,3.64 mmol) and methanesulfonyl chloride (0.375 mL,4.85 mmol) at 0 ℃. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (30% ethyl acetate/hexane) and indicated no starting material. The reaction mixture was diluted with water (50.0 mL) and extracted with EtOAc (2X 50 mL). The combined organic layers were washed with brine (30 mL), and dried over Na ₂ SO ₄ Dried and concentrated under reduced pressure to give the crude title compound as a yellow solid.

The compound was sent to the following step without purification.

MS:m/z＝473.8[M+2H] ⁺ 。

Step 5:6- [ [ 5-bromo-2- (3-chloro-2-pyridinyl) pyrazole-3-carbonyl]Amino group]Preparation of-2, 5-dimethyl-1, 3-benzoxazole-7-carboxamide (Compound P.20)

A 25mL two-necked round bottom flask was equipped with a nitrogen balloon and 7- [ 5-bromo-2- (3-chloro-2-pyridinyl) pyrazol-3-yl ] -2, 5-dimethyl-oxazolo [5,4-f ] [3,1] benzoxazin-9-one (preparation described above) (200 mg,0.423 mmol) in acetonitrile (5.0 mL) was added thereto and ammonia (2M in ethanol) (2.0 mL) was added at room temperature. The resulting reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was analyzed by TLC (10% MeOH/DCM) and indicated no starting material. The reaction mixture was concentrated under reduced pressure to give a crude residue which was purified by combi flash,0% to 100% acetonitrile/water. The pure fractions were combined and evaporated under reduced pressure to give the title compound as an off-white solid.

¹ H NMR(400MHz,DMSO-d ₆ ):δ10.31(s,1H),8.49(dd,J＝4.8Hz,1.6Hz,1H),8.15(dd,J＝8.4Hz,1.6Hz,1H),7.74(s,1H),7.67(s,1H),7.61-7.58(m,2H),7.39(s,1H),2.60(s,3H),2.22(s,3H)；

MS:m/z＝491.0[M+2H] ⁺ 。

Melting point >250 ℃.

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By adding further insecticidal, acaricidal and/or fungicidal active ingredients, the activity of the composition according to the invention can be considerably broadened and adapted to the prevailing circumstances. Mixtures of the compounds of the formula I with other insecticidal, acaricidal and/or fungicidal active ingredients can also have further surprising advantages which can also be described in a broader sense as synergistic activity. For example, better tolerance of plants, reduced phytotoxicity, better behaviour of insects can be controlled at their different developmental stages, or during their production (e.g. during grinding or mixing, during their storage or during their use).

Suitable active ingredients to be added here are, for example, representatives of the following classes of active ingredients: organophosphorus compounds, nitrophenol derivatives, thiourea, juvenile hormone, formamidine, benzophenone derivatives, urea, pyrrole derivatives, carbamate, pyrethroid, chlorinated hydrocarbon, acylurea, pyridylmethylene amino derivatives, macrolides, neonicotinoids and bacillus thuringiensis formulations.

The following mixture of compounds of formula I with active substances is preferred (the abbreviation "TX" means "one compound selected from the compounds defined in table X, table Xa and table P"):

an adjuvant selected from the group consisting of: petroleum (alias) (628) +TX, abamectin+TX, methoquinone+TX, acetamiprid+TX, acetylnitrile+TX, fluoropropyl pyrethrin+TX, axinol (Acynonapyr) +TX, dipropyl cyclic ester+TX, afrana (afoxolane) +TX, cotton bolcarb+TX, allethrin+TX, alpha-cypermethrin+TX, sulfamethazine+TX, methoprene+TX, triazotin+TX, monosulfan+TX, bennett+TX, topiramate (benzpyrimoxan) +TX, beta-cyhalothrin+TX, Bifenazate+tx, tebufenpyrad+tx, bioallethrin+tx, S-bioallethrin+tx, biobifenazate+tx, bistrifluron+tx, brofenfluramine (brofililide) +tx, brofipronil+tx, brofenphos-ethyl+tx, buprofezin+tx, butanone+tx, thiotepa+tx, carbaryl+tx, carbosulfan+tx, bardan+tx, CAS number: 1632218-00-8+TX, CAS number: 1808115-49-2+TX, CAS number: 2032403-97-5+TX, CAS number: 2044701-44-0+TX, CAS number: 2128706-05-6+TX, CAS number: 2095470-94-1+TX, CAS number: 2377084-09-6+TX, CAS number: 1445683-71-5+TX, CAS number: 2408220-94-8+TX, CAS number: 2408220-91-5+TX, CAS number: 1365070-72-9+TX, CAS number: 2171099-09-3+TX, CAS number: 2396747-83-2+TX, CAS number: 2133042-31-4+TX, CAS number: 2133042-44-9+TX, CAS number: 1445684-82-1+TX, CAS number: 1445684-82-1+TX, CAS number: 1922957-45-6+TX, CAS number: 1922957-46-7+TX, CAS number: 1922957-47-8+TX, CAS number: 1922957-48-9+TX, CAS number: 2415706-16-8+TX, CAS number: 1594624-87-9+TX, CAS number: 1594637-65-6+TX, CAS number: 1594626-19-3+TX, CAS number: 1990457-52-7+TX, CAS number: 1990457-55-0+TX, CAS number: 1990457-57-2+TX, CAS number: 1990457-77-6+TX, CAS number: 1990457-66-3+TX, CAS number: 1990457-85-6+TX, CAS number: 2220132-55-6+TX, CAS number: 1255091-74-7+TX, CAS number: RNA (potato beetle-specific recombinant double-stranded interference GS 2) +tx, CAS number: 2719848-60-7+TX, CAS number: 1956329-03-5+ TX, chlorantraniliprole+ TX, chlordane+ TX, chlorantraniliprole+ TX, chlorpropathrin+ TX, chromafenozide+ TX, clenpyraline+ TX, carboline (clomethocarb) +TX, clothianidin+ TX, 2-chlorophenyl N-methyl carbamate (CPMC) +TX, cyanophos+ TX, cyantraniliprole+ TX, cyclobridiamide+ TX, cyclo Ding Fulun (cyclobutrifluram) +TX, pyrethroid+ TX, cycloxapridine+ TX, cyenopyrafen+ TX, cytebufenpyrad+ TX, fenpyrad-ethyl Cyclopyralid (cyethyrafen or etpyrafen) +TX, cyflumetofen+TX, cyfluthrin+TX, cyhalodiamide (cyhalodiamide) +TX, cyfluthrin+TX, cypermethrin+TX, fencythrin+TX, cyclopropflubenide (cyprofaniide) +TX, cyromazine+TX, deltamethrin+TX, acaricide+TX, chlorpyrifos+TX, dibromophosphorus (dibrom) +TX, dichloropyrimidine (dicyclomazoiaz) +TX, flufenzine+TX, avermectin Urea+tx, oxazinamide (dimropyridaz) +tx, divomycin+tx, difenpropi+tx, dinotefuran+tx, vegetable and fruit phosphorus+tx, emamectin (or emamectin benzoate) +tx, dextromethorphan+tx, epsilon-mofipronil) +tx, epsilon-methoxybenfipronil+tx, fenvalerate+tx, ethidium+tx, ethiprole+tx, fipronil+tx Ethyl chrysanthemate+TX, etoxazole+TX, valinate+TX, fenazaquin+TX, penflufen+TX, fenbendazole dititaaz+TX, fenitrothion+TX, fenobucarb+TX, benfuracarb+TX, fenoxycarb+TX, fenpropathrin+TX, fenpyroximate (fenpyroximate) +TX, fenphos+TX, she Sailing +TX, fenvalerate+TX, fipronil+TX, fenbuconazole+TX fipronil (fipronil) +tx, flonicamid+tx, azoxystrobin+tx, trifluramide (fluzaindolizine) +tx, pyrifos urea+tx, fipronamide+tx, fluvalothiazid+tx, flucloxadiamide (fluchloriniliprogril) +tx, flusilate (flucitinate) +tx, flucyclomide+tx, flufenvalerate+tx, fluthiamethoxam+tx, azomethide+tx, trifluramide+tx, butene fipronil+tx, fluhexafon (fluhexafon) +tx, flumethrin+tx, flupyrazuron+tx, flufenhexax (flufluazafenox) +tx, flupyrazodone+tx, flupirtine (fluirimin) +tx, flu Lei Lana (flusalanate) +tx, flufenprox TX, fludec+tx, fluflufenmid+tx, fluvalinate+fluvalinate+tx, flufenitrox+flufenitrox, flufenx+flufenx Penflufen+tx, chlorfenozide+tx, fenacet+tx, tefluthrin (hepteluthrin) +tx, hexythiazox+tx, flumetzonone+tx, imidazophos (imicyafos) +tx, imidacloprid+tx, propathrin+tx, indapamide (indapapyroxamet) +tx, indoxacarb+tx, methyl iodide+tx, iprodione+tx, isoxazolamide (isocycloseram) +tx, isoxafluthrin+tx, ivermectin+tx, kappa-bifenthrin+tx, kappa-tefluthrin+tx, lambda-cyhalothrin+tx, fenuron+tx, fluazuron+tx, tetramethrin+tx, methoprene+tx, flunixin+tx; nitenpyram+TX, omethoate+TX, methoprene+TX, methomyl+TX, Oxazophos (oxathiolfyl) +tx, parathion-ethyl+tx, permethrin+tx, phenothrin+tx, phospho-ethyl+tx, piperonyl butoxide+tx, pirimicarb+tx, pyrimidophos-ethyl+tx, pyrimidophos-methyl (pirimiphos-methyl) +tx, polyhedrosis virus+tx, propathrin+tx, profenofos+tx, profenox+tx, propoxur+tx, profenox+tx, propyl pyrimidone+tx, propyl fenprox+tx, pytriamid+tx, pymetrozine+tx, pyrazophos+tx, pyrimidone+tx, fluazifop-pran (pyriquizon) +tx, pyrimidone+tx, flufenpyrad+tx, fluben+tx, flubenfop+tx; spirodiclofen+tx, spiromesifen+tx, methoprene ethyl (spirotetramat) +tx, spirotetramat+tx, span Ai Mate (spidoxamat) +tx, sulfenpyrad+tx, tebufenozide+tx, tebufenpyrad+tx, butyl pyrifos (tebupirimiphos) +tx, tefluthrin+tx, dithiophosphate+tx, tetrachlorpyrimide+tx, tetrachlor-mite sulfone (tetrabiphon) +tx, tetramethrin+tx, tetrafipronate+tx, acaricide+tx, flucyantranide+tx, θ -cypermethrin+tx, thiacloprid+tx, thiamethoxam+tx, thiocyclam+tx, monocrotophos+tx, methyl ethyl phosphorus+tx, sulcotrione+tx, tigo-sodium (tigo lan) +tx, thiamethoxam (tiopron) +pro) +tx; thiophene (tioxazafen) +TX, tolfenpyrad+TX, toxafen+TX, tetrabromothrin+TX, tebufenpyrad+TX, triazamate+TX, triazophos+TX, trichlorfon+TX, chlorfenapyr+TX, trichlorfon+TX, Trifloxystrobin (trifluenfuronate)+TX, trifluorobenzene pyrimidine (triflumezopyrazolide) +TX, chlorpyraclostrobin (tyropyrazolor) +TX, zeta-cypermethrin+TX, seaweed extract and fermentation product derived from sugar acyl +TX, seaweed extract and fermentation product derived from sugar acyl (comprising urea +TX, amino acids +TX, potassium and molybdenum and EDTA chelated manganese) +TX, seaweed extract and fermented plant product (comprising phytohormone +TX, vitamin +TX, EDTA chelated copper +TX, zinc +TX, and iron +TX), azadirachtin +TX, bacillus catus(Bacillus aizawai) +TX, bacillus chitinans (Bacillus chitinosporus) AQ746 (NRRL accession number B-21618) +TX, bacillus firmus+TX, bacillus kurth (Bacillus kurstaki) +TX, bacillus mycosporus AQ726 (NRRL accession number B-21664) +TX, bacillus pumilus (NRRL accession number B-30087) +TX, bacillus pumilus AQ717 (NRRL accession number B-21662) +TX, bacillus species AQ178 (ATCC accession number 53522) +TX, bacillus species AQ175 (ATCC accession number 55608) +TX, bacillus species AQ177 (ATCC accession number 55609) +TX, unspecified Bacillus+TX, bacillus subtilis AQ153 (ATCC accession number 55614) +TX, bacillus subtilis AQ30002 (NRRL accession number B-50421) +TX) Bacillus subtilis AQ30004 (NRRL accession number B-50455) +TX, bacillus subtilis AQ713 (NRRL accession number B-21661) +TX, bacillus subtilis AQ743 (NRRL accession number B-21665) +TX, bacillus thuringiensis AQ52 (NRRL accession number B-21619) +TX, bacillus thuringiensis BD#32 (NRRL accession number B-21530) +TX, bacillus thuringiensis subspecies (subspecies. Kurstaki) BMP+TX, beauveria bassiana+TX, D-limonene+TX, granulovirus+TX, kang Zhuangsu (Harpin) +TX, cotton bollworm nuclear polyhedrosis virus+TX, cereal noctuid nuclear polyhedrosis virus+TX, spodoptera frugiperda nuclear polyhedrosis virus+TX, australian cotton nuclear polyhedrosis virus+TX, pythia nuclear polyhedrosis virus, metarhizium species +tx, malodorous white fungus (Muscodor albus) 620 (NRRL accession number 30547) +tx, malodorous rose fungus (Muscodor roseus) A3-5 (NRRL accession number 3048) +tx, neem tree-based product +tx, paecilomyces fumosoroseus +tx, paecilomyces lilacinus +tx, paenibacillus pseudoszewalteus +tx, papanicolaou +tx, mycobacterium +tx, cable Lei Bashi bacillus (Pasteuria thornei) +tx, papanicolaou +tx, p-cymene +tx, plutella xylostella granulosis virus +tx, plutella xylostella nuclear polyhedrosis virus +tx, pyrethrum +tx, QRD 420 (terpenoid blend) +tx, QRD 452 (terpenoid blend) +tx, QRD 460 (terpenoid blend) +tx, soap tree +tx, rhodococcus globosa +tx 719 (nrrl+ 21663) +b+tx, kusnezoffii-side nula +tsumadai +tsun-35, nrichond +myces +35, and nrichondria +16+streptomyces +myces +35;

An algicide selected from the group consisting of: baishazin (bethoxazin) [ CCN ] +tx, copper dioctanoate (IUPAC name) (170) +tx, copper sulfate (172) +tx, ciprofloxacin (cybutryne) [ CCN ] +tx, dichlorophenone (dichlorine) (1052) +tx, dichlorophenol (232) +tx, chlorantoid (295) +tx, triphenyltin (Fentin) (347) +tx, slaked lime [ CCN ] +tx, sodium (nabam) (566) +tx, algicidal quinone (quinic amine) (714) +tx, quinone amine (quininamid) (1379) +tx, simazine (730) +tx, triphenyltin acetate (IUPAC name) (347), and triphenyltin hydroxide (IUPAC name) (347) +tx;

an anthelmintic agent selected from the group consisting of: avermectin (1) +TX, krephosphite (1011) +TX, cyclo Ding Fulun +TX, doramectin (alias) [ CCN ] +TX, emamectin (291) +TX, emamectin benzoate (291) +TX, eprinomectin (alias) [ CCN ] +TX, ivermectin (alias) [ CCN ] +TX, milbemycin oxime (alias) [ CCN ] +TX, moxidectin (alias) [ CCN ] +TX, piperazine [ CCN ] +TX, selamectin (alias) [ CCN ] +TX, spinosad (737), and thiophanate (1435) +TX;

a bird killer selected from the group consisting of: aldochloroses (127) +tx, additives (1122) +tx, phoxim (346) +tx, pyridin-4-amine (IUPAC name) (23) and strychnine (745) +tx;

A bactericide selected from the group consisting of: 1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222) +TX, 4- (quinoxalin-2-ylamino) benzenesulfonamide (IUPAC name) (748) +TX, 8-hydroxyquinoline sulfate (446) +TX, bromonitro alcohol (97) +TX, copper dioctate (IUPAC name) (170) +TX, copper hydroxide (IUPAC name) (169) +TX, cresol [ CCN ] +TX, dichlorophenol (232) +TX, bipyralid (1105) +TX, doxine (1112) +TX, sodium disulfone (fenaminosf) (1144) +TX, formaldehyde (404) +TX, mercuric plus (alias) [ CCN ] +TX, kasugamycin (483) +TX, kasugamycin hydrochloride hydrate (483) +TX, bis (dimethyldithiocarbamate) nickel (PAC name) (1308) +TX, trichlorethylpyridine (nipy) (580) +TX, xin Saitong) (lymphomycin sulfate) (590, oltipraz (606), doxycycline (766) +, doxycycline (766) +sulfate (744) and streptomycin sulfate (744);

a biological agent selected from the group consisting of: the species Apostigma littoralis GV (alias) (12) +TX, agrobacterium radiobacter (alias) (13) +TX, amblyseius spp (alias) (19) +TX, apostigma apiacea NPV (alias) (28) +TX, oenoptera primordica Anagrus (Anagrus atoms) (alias) (29) +TX, apostigma brachypus (Aphelinus abdominalis) (alias) (33) +TX, apostigma gossypii parasitic wasp (Aphidius colemani) (alias) (34) +TX, aphidius gifuensis (Aphidoletes aphidimyza) (alias) (35) +TX, apostigma medica NPV (alias) (38) +TX, bacillus firmus (Bacillus firmus) (alias) (48) +TX) Bacillus sphaericus (Bacillus sphaericus Neide) (academy) (49) +TX, bacillus thuringiensis (Bacillus thuringiensis Berliner) (academy) (51) +TX, bacillus thuringiensis catfish subspecies (Bacillus thuringiensis subsp. Aizawai) (academy) (51) +TX, bacillus thuringiensis subspecies (Bacillus thuringiensis subsp. Israeli) (academy) (51) +TX, bacillus thuringiensis subspecies (Bacillus thuringiensis subsp. Japonensis) (academy) (51) +TX, bacillus thuringiensis subspecies (Bacillus thuringiensis subsp. Kurstaki) (academy) (51) +TX), bacillus thuringiensis is intended to be by the genus Methania (Bacillus thuringiensis subsp. Tenebrionis) (academic) 51) +TX, beauveria bassiana Beauveria bassiana (aliases) 53) +TX, beauveria bassiana Beauveria brongniartii (aliases) 54) +TX, fabryozoa (Chrysoperla carnea) (aliases) 151) +TX, cryptolepis mandshurica Cryptolaemus montrouzieri (aliases) 178) +TX, codling moth GV (aliases) 191 (aliases) TX, siberian from the jaw cocoon bee (Dacanula sibirica) 212 (aliases) TX, pisum sativum She Yingji small bee (Diglyphus isaea) aliases (aliases) 254) +TX, aphis pomonensis (Encarsia fortis) for the chemical name TX (293) +TX, aphis pratensis Eretmocerus eremicus) (300) +TX, novata NPV (aliases) 431 TX, heteropapilis (Heterorhabditis bacteriophora) and Lepidogyra sp H.ensii (62) +) can be placed in the blood vessel (fig. 39) +, metarhizium anisopliae (Metarhizium anisopliae var. Acridum) (academic name) (523) +TX, metarhizium anisopliae microsporoseum variety (Metarhizium anisopliae var. Aniopliae) (academic name) (523) +TX, new european pine needle (Neodiprion sertifer) NPV and new red pine needle (N.lecontei) NPV (alias) (575) +TX, cerjous species (alias) (596) +TX, paecilomyces fumosoroseus (Paecilomyces fumosoroseus) (alias) (613) +TX, small white fungus small plant mite (Phytoseiulus persimilis) (alias) (644) +TX, beet moth nuclear polyhedrosis virus (Spodoptera exigua multicapsid nuclear polyhedrosis virus) (academic name) (741) +TX, mao Wen nematode (Steinernema bibionis) (alias) (742) +TX, small leaf roller nematode (Steinernema carpocapsae) (alias) (742) +TX, night moth (742) +TX, TX) (Steinernema glaseri) (742) +TX, sharp us species (Steinernema riobrave) (7432) (742) +PYPRESTERIUM (742) +Tx, fig. 5 alias TX) +PYPRESTERIUM species (742) +STYPRUM (742) (TKyotis (742) (TXYRIUM) Western blind spider mites (Typhlodromus occidentalis) (alias) (844) and verticillium lecanii (Verticillium lecanii) (alias) (848) +tx;

A soil disinfectant selected from the group consisting of: methyl iodide (IUPAC name) (542) and methyl bromide (537) +tx;

a chemosterilant selected from the group consisting of: azophos (apholate) [ CCN ] +TX, bis (aziridine) methylaminophosphine sulfide (bisazir) (alias) [ CCN ] +TX, busulfan (alias) [ CCN ] +TX, diflubenzuron (250) +TX, dimetif (dimatif) (alias) [ CCN ] +TX, altretamine (hemel) [ CCN ] +TX, altfophos (hempa) [ CCN ] +TX, methylaldiba (metepa) [ CCN ] +TX, methylthioaldiba (methyoepa) [ CCN ] +TX, methylphospholazine (methyholate) [ CCN ] +TX, infertility (moving zid) [ CCN ] +TX, fluoroyoung urea (penfluron) (CCN ] +TX, bars (tepa) [ CCN ] +TX, thiohexamethylphosphorus (hempa) [ CCN ] +TX, thiohexamethylphosphorus (thia) [ CCN ] +TX, thioaldimine (CCN ] +alias, [ CCN ] +alias ] [ thioimine ] (thioimine ] [ CCN ];

an insect pheromone selected from the group consisting of: (E) -dec-5-en-1-yl acetate and (E) -dec-5-en-1-ol (IUPAC name) (222) +TX, (E) -tridec-4-en-1-yl acetate (IUPAC name) (829) +TX, (E) -6-methylhept-2-en-4-ol (IUPAC name) (541) +TX, (E, Z) -tetradec-4, 10-dien-1-yl acetate (IUPAC name) (779) +TX, (Z) -dodeca-7-en-1-yl acetate (IUPAC name) (285) +TX, (Z) -hexadec-11-en aldehyde (IUPAC name) (436) +TX, (Z) -hexadec-11-en-1-yl acetate (IUPAC name) (438) +TX, (Z) -hexadec-13-en-11-en-1-yl acetate (IUPAC name) (448) + (Z) -hexadec-7-en-1-yl acetate (IUPAC name) (782) +TX, (Z) -hexadec-13-en-10-one (IUPAC name), (Z) -tetradec-9-en-1-ol (IUPAC name) (783) +TX, (Z) -tetradec-9-en-1-yl acetate (IUPAC name) (784) +TX, (7E, 9Z) -dodeca-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-yl acetate (IUPAC name) (781) +TX, 14-methyl octadec-1-ene (IUPAC name) (545) +TX, 4-methyl non-5-ol and 4-methyl non-5-one (IUPAC name) (544) +TX, alpha-multi-texin) (alias) [ CCN ]+TX, west Pinus bark beetle aggregate pheromone (bricomin) (alias) [ CCN ]]+TX, dodecadienol (alias) [ CCN ]]+TX, available Mongolian (codlemone) (alias) (167) +TX, coumesone (cure) (alias) (179) +TX, epoxynonadecane (disparet) (277) +TX, dode-8-en-1-yl acetate (IUPAC name) (286) +TX, dode-9-en-1-yl acetate (IUPAC name) (287) +TX, dode-8+TX, 10-dien-1-yl acetate (IUPAC name) (284) +TX, polyminolure (alias) [ CCN]+TX, ethyl 4-methyl octanoate (IUPAC name) (317) +TX, eugenol (alias) [ CCN ]]+TX, southern pine bark beetle aggregate pheromone (alias) [ CCN ]]+TX、1:1 mixtures (420) +TX, trapping olefine mixture (grandole) (421) +TX, trapping olefine mixture I (alias) (421) +TX, trapping olefine mixture II (alias) of (Z, E) and (Z, Z) isomers of (alias; hexadec-7, 11-dien-1-yl-acetate)) (421) +TX, decoy III (alias) (421) +TX, decoy IV (alias) (421) +TX, and hexalur [ CCN ]]+TX, bark beetle dienol (alias) [ CCN ]]+TX, silly enol (alias) [ CCN ]]+TX, chafer sex attractant (alias) (481) +TX, trimethyldioxytricyclononane (linetin) (alias) [ CCN ] ]+TX, noctuid sex attractant (litlure) (alias) [ CCN ]]+TX, spodoptera frugiperda sex attractant (alias) [ CCN ]]+TX, trapping ester (med lure) [ CCN ]]+TX, (3E, 5Z) -tetradecyl-3, 5-dienoic acid (alias) [ CCN ]]+TX, seduction ether (methyl eugenol) (alias) (540) +TX, seduction alkene (mu scale) (563) +TX, octadeca-2, 13-dien-1-yl acetate (IUPAC name) (588) +TX, octadeca-3, 13-dien-1-yl acetate (IUPAC name) (589) +TX, he Kangbi (orfrale) (alias) [ CCN)]+TX, cocois Rhinocerotis (alias) (317) +TX, folum Ilicis (alias) [ CCN ]]+TX, trap (CCN)]+TX, banana bulb weevil attractant (sordidn) (alias) (736) +TX, edible fungus methyl attractant alcohol (surcatol) (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, and Mediterranean fruit fly attractant B ₁ (alias) (839) +TX, mediterranean fruit fly attractant B ₂ (alias) (839) +TX, drosophila Medicata attractant C (alias) (839) and trunk-call (alias) [ CCN ]]+TX；

An insect repellent selected from the group consisting of: 2- (octylthio) ethanol (IUPAC name) (591) +tx, mosquito-repellent ketone (butopyronoxy) (933) +tx, butoxy (polypropylene glycol) (936) +tx, dibutyl adipate (IUPAC name) (1046) +tx, dibutyl phthalate (1047) +tx, dibutyl succinate (IUPAC name) (1048) +tx, mosquito-repellent amine [ CCN ] +tx, mosquito-repellent (dimethyl carbate) [ CCN ] +tx, dimethyl phthalate [ CCN ] +tx, ethylhexyl glycol (1137) +tx, hexylurea [ CCN ] +tx, mequindine (methoquin-butyl) (1276) +tx, methyl neodecanoamide [ CCN ] +tx, oxamate [ CCN ] and pekriging [ CCN ] +tx;

A molluscicide selected from the group consisting of: di (tributyltin) oxide (IUPAC name) (913) +tx, bromoacetamide [ CCN ] +tx, calcium arsenate [ CCN ] +tx, triamcinolone (999) +tx, copper acetylarsenite [ CCN ] +tx, copper sulfate (172) +tx, triphenyltin (347) +tx, iron phosphate (IUPAC name) (352) +tx, metaldehyde (518) +tx, methomyl (530) +tx, niclosamide (576) +tx, niclosamide-ethanolamine (576) +tx, pentachlorophenol (623) +tx, sodium pentachlorobenzene oxide (623) +tx, thiamethomyl (tazimcarb) (1412) +tx, thiodicarb (799) +tx, tributyltin oxide (913) +tx, snail killing (trimethorph) (1454) +tx, mixed insecticidal pac (840) +tx, triphenyltin acetate (347) and triphenyltin hydroxide (IUPAC) (347) +60) +pyridine (3-35) +pyridine (73) +pyridine;

a nematicide selected from the group consisting of: AKD-3088 (compound code) +tx, 1, 2-dibromo-3-chloropropane (IUPAC/chemical abstract name) (1045) +tx, 1, 2-dichloropropane (IUPAC/chemical abstract 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 abstract name) (1065) +tx, 3- (4-chlorophenyl) -5-methyl rhodanin (IUPAC name) (980) +tx, 5-methyl-6-thio-1, 3, 5-thiadiazin-3-ylacetic acid (IUPAC name) (1286) +tx, 6-isopentenylaminopurine (TX) (210) +tx, abamectin (IUPAC name) (1063) +tx, acetylworm nitrile [ CCN ] +tx, cotton bolone (15) +tx, carbosulfan (TX), carbosulfan (62) +, AZ (62) +4-chloranin) +6, AZ (35), 3-propylsulfan (60) +, 3-thio) and (60) +6-thio) carbosulfan (IUPAC name) (35), 5) +6-thio-6-thio-1, 5-thiadiazin (IUPAC name) (1286) +tx), 5-methyl-6) +x, 6) +6-isopentenyl (TX) +tx (210) +x, 6) +6-isopropyl (TX, 6) +, chlorpyrifos (145) +TX, desmethylwire (999) +TX, cyclo Ding Fulun +TX, cytokinin (alias) (210) +TX, dazomet (216) +TX, DBCP (1045) +TX, DCIP (218) +TX, desmethylwire (diamidafos) (1044) +TX, desmphos (1051) +TX, dicarbox (dicyclophos) (alias) +TX, dimethoate (262) +TX, doramectin (alias) [ CCN ] +TX, emamectin (291) +TX, emamectin benzoate (291) +TX, irinotecan (alias) [ CCN ] +TX, desmos (312) +TX, dibromoethane (316) +TX, benline phosphorus (326) +TX tebufenpyrad (fenpyrad) (alias) +TX, feng Suolin (1158) +TX, fosthiazate (408) +TX, buthion (1196) +TX, furfuraldehyde (alias) [ CCN ] +TX, GY-81 (research code) (423) +TX, thiophosphorus [ CCN ] +TX, methyl iodide (IUPAC name) (542) +TX, isoamidophos (isamidofos) (1230) +TX, chlorzophos (1231) +TX, ivermectin (alias) [ CCN ] +TX, kinetin (alias) (210) +TX, methylprednisolone (1258) +TX, wilms (519) +TX, wilms potassium salt (alias) (519) +TX The composition comprises a sodium salt of wire (519) +TX, bromomethane (537) +TX, methyl isothiocyanate (543) +TX, milbexime (alias) [ CCN ] +TX, moxidectin (alias) [ CCN ] +TX, a composition of verrucosa (Myrothecium verrucaria) including (alias) (565) +TX, NC-184 (compound code) +TX, wire-killing wire (602) +TX, methamphetamine (636) +TX, phospham (639) +TX, phosphorus worm [ CCN ] +TX, clarinone (alias) +TX, selametin (alias) [ CCN ] +TX, spinosad (737) +TX, tertbutycarb (alias) +TX, tertbutylphos (773) +TX, tetrachlorothiophene (IUPAC/chemical digest name) (1422) +TX, thiophene (thox) (alias TX) +TX, insect wire phosphorus (1434) +TX, phosphorus (820) +triazophos (triazu (636) +TX), triazophos (35-35) and (Yzu 35-35) including (alias) and (35-Fluo (alias) including (alias) and (alias) including (35);

A nitrification inhibitor selected from the group consisting of: potassium ethylxanthate [ CCN ] and chloropyridine (580) +tx;

a plant activator selected from the group consisting of: ala acid benzene (acibenzolar) (6) +TX, ala acid benzene-S-methyl (6) +TX, thiabendazole (658) and giant knotweed (Reynoutria sachalinensis) extract (alias) (720) +TX;

a rodenticide selected from the group consisting of: 2-isovalerylindan-1, 3-dione (IUPAC name) (1246) +TX, 4- (quinoxalin-2-ylamino) benzenesulfonamide (IUPAC name) (748) +TX, alpha-chlorohydrin [ CCN ] +TX, aluminum phosphide (640) +TX, anto (880) +TX, arsenic trioxide (882) +TX, barium carbonate (891) +TX, bismurine urea (912) +TX, bromomurine (89) +TX, bromodiuron (including alpha-bromodiuron) +TX, bromomurine amine (92) +TX, calcium cyanide (444) +TX, chloroaldehyde sugar (127) +TX, chloromurine ketone (140) +TX, cholecalciferol (alias) (850) +TX) clomazone (1004) +TX, clomazone (1005) +TX, deratization naphthalene (175) +TX, deratization pyrimidine (1009) +TX, muodex (246) +TX, thiabendazole (249) +TX, diphacinone (273) +TX, calciferol (301) +TX, fluoromous (357) +TX, fluoroacetamide (379) +TX, fluoromous pyridine (1183) +TX, fluoromous pyridine hydrochloride (1183) +TX, gamma-HCH (430) +TX, hydrogen cyanide (444) +TX, methyl iodide (IUPAC name) (542) +TX, lindan (430) +TX, magnesium phosphide (IUPAC name) (640) +TX, methyl bromide (537) +tx, mouse telnet (1318) +tx, mouse phosphorus (1336) +tx, phosphine (IUPAC name) (640) +tx, phosphorus [ CCN ] +tx, raticide (1341) +tx, potassium arsenite [ CCN ] +tx, mouse killer (1371) +tx, chives glucoside (1390) +tx, sodium arsenite [ CCN ] +tx, sodium cyanide (444) +tx, sodium fluoroacetate (735) +tx, strychnine (745) +tx, thallium sulfate [ CCN ] +tx, mouse killer (851), and zinc phosphide (640) +tx;

A potentiator selected from the group consisting of: 2- (2-butoxyethoxy) ethyl piperonate (IUPAC name) (934) +tx, 5- (1, 3-benzodioxol-5-yl) -3-hexylcyclohex-2-enone (IUPAC name) (903) +tx, farnesol (alias) with nerolidol (324) +tx, MB-599 (research code) (498) +tx, MGK 264 (research code) (296) +tx, synergistic ether (piperonyl butoxide) (649) +tx, synergistic aldehyde (piportal) (1343) +tx, synergistic ester (propyl iscomer) (1358) +tx, S421 (research code) (724) +tx, synergistic powder (sesamex) (1393) +tx, sesamin (sesamolin) (1394), and sulfoxide (1406) +tx;

an animal repellent selected from the group consisting of: anthraquinone (32) +tx, chloral candy (127) +tx, copper naphthenate [ CCN ] +tx, copper (171) +tx, diazinon (227) +tx, dicyclopentadiene (chemical name) (1069) +tx, bispentalene (chemical name) (422) +tx, bisguanosine acetate (422) +tx, methomyl (530) +tx, pyridin-4-amine (IUPAC name) (23) +tx, zeram (804) +tx, methocarb (trimethacarb) (840) +tx, zinc naphthenate [ CCN ] and fomesan (856) +tx;

a virucide selected from the group consisting of: garment Ma Ning (alias) [ CCN ] and ribavirin (alias) [ CCN ] +tx;

A wound protecting agent selected from the group consisting of: mercuric oxide (512) +tx, xin Saitong (octilinone) (590) and thiophanate methyl (802) +tx;

the bioactive substance is a bioactive substance that, the bioactive substance is selected from 1, 1-bis (4-chloro-phenyl) -2-ethoxyethanol+TX, 2, 4-dichlorophenyl benzenesulfonate+TX, 2-fluoro-N-methyl-N-1-naphthaleneacetamide+TX, 4-chlorophenyl phenyl sulfone+TX, acetylchlorfenapyr+TX, aldicarb+TX, racefruit+TX, dial-p+TX, amine phosphorus+TX, hydrogen amine phosphorus+TX, amitraz+TX, acaricide+TX, arsenic trioxide+TX, azobenzene+TX, azo phosphorus+TX, benomyl+TX, benoxfos+TX, benzyl benzoate+TX, bipyramid+TX, brofenthrin+TX, bromoolefin+TX, bromothiophos+TX, bromomite+TX, buprofezin+TX, butyl pyridaben+TX, calcium doxofyllide+TX octachlorcamphene+tx, chlorpyrifos+tx, trithion+tx, fenpicloram+tx, acephate+tx, fenhexamid+tx, amitraz+tx, acephate+tx, fenhexamid+tx, chlormebuform+tx, chlormeurea+tx, propyl ester fenhexamid+tx, fenphos+tx, fenthrin i+tx, fenthrin ii+tx, fenthrin+tx, clomestrane+tx, coumaphos+tx, clomiphos+tx, bafipron+tx, thiazalin+tx, chlormefos+tx, ddt+tx, tenphos+tx, tenphos-o+tx, tenphos-s+tx, endophos-methyl+tx, endo-O-methyl+tx, endo-phos-O-methyl+tx, in-S+TX, in-S-methyl+TX, sulfoin (dimet-S-methyl-fonn) +TX, dichlorvos+TX, dicyclophos+TX, furin+TX, meflophos+TX, abamectin (dinex) +TX, abamectin-dicyclexine) +TX, dimite 4+TX, dimite 6+TX, adjacent dimite+TX, nitron+TX, nitron+acaricide+TX, nitron+TX, diphos+TX, sulfodiphenyl+TX, alcohol-stopping sulfur+TX, DNOC+TX, phenoxymite (dofenapyn) +TX, dorametin+TX, meflon+TX, irinotetin+TX, yithiophos+TX, ethirimethyl+TX, anti-mite+TX, bentin+TX, benfurin+TX, fenbufen+TX, fenphos+fenphos+TX, fenpyrad+TX, dipyr+TX, fenpropin+TX, fenpyrad+TX, dorin+TX; fenisobornyl+tx, flunifanil (fenrifanil) +tx, flucyclox+tx, bifenthrin+tx, flufenphos+tx, FMC 1137+tx, valacimidine+tx, valacimidine hydrochloride+tx, carboxin (formaranate) +tx, gamma-hch+tx, levalidine+tx, benfurin+tx, cetyl cyclopropane carboxylate+tx, water amine thiophosphor+tx, jasmine l+tx, jasmine ii+tx, iodine thiophosphor+tx, lindan+tx, propargin+tx, acephate+tx, dithiphos+tx, methiphos+tx, fenbufenn+tx, bromomethane+tx, speed mevalicarb+tx, milbexime+tx, propamocarb+tx, promethazine+tx, cyclon+tx, dibromophosphorus (naled) +tx, 4-chloro-2- (2-chloro-2-methyl-propyl) -5- [ (6-iodo-3-pyridinyl) methoxy ] pyridazin-3-one+TX, flumetsulam+TX, nikkomycin+TX, pentacarbofuran+TX, pentacarbofuran 1:1 zinc chloride complex+TX, omethoate+TX, isosulfone phosphorus+TX, sulfone phosphorus+TX, pp' -DDT+TX, parathion+TX, permethrin+TX, fenphos+TX, fungicide+TX, thiocyclophosphorus+TX, phospham+TX, turpentine (polychlorotes) +TX, acaricide (polynaphins) +TX, prochloraz+TX, tick carbofuran+TX, propoxur+TX, ethionazole+TX, fos+TX, pyrethrin I+TX, pyrethrin II+TX, pyrethrin+TX, pyridazinethion+TX, pyrithione+TX, quinalphos) + quinophos (quintiofos) +tx, R-1492+tx, glycithion+tx, rotenone+tx, octamethiphos+tx, captan+tx, selacin+tx, su Liu phosphorus+tx, SSI-121+tx, shu Feilun +tx, flubendiamide+tx, thitebufos+tx, thio+tx, flubenazine+tx, τ -flufenthrinate+tx, tepp+tx, t-carbofuran+tx, tetrachlorethos+tx, miticidal good+tx, thiafenox+tx, indoxacarb+tx, monocrotophos+tx, methyl ethasone+tx, kemite+tx, threomycin+tx, valfacine+tx, triazophos+tx, imazazole (triazuron) +tx, tricloproppole+tx, trioxyphos+tx, triazophos+tx, methide+tx, methimazole (vanadpriprozin) + Baishazin (bethoxazin) +tx, copper dioctanoate+tx, copper sulfate+tx, cyclopropanid+tx, dichlorophenoquinone+tx, dichlorophenol+tx, chlorphenamine+tx, triphenyltin+tx, slaked lime+tx, zinon+tx, chlorazolin+tx, quinolylamine+tx, simazine+tx, triphenyltin acetate+tx, triphenyltin hydroxide+tx, yunnan+tx, piperazine+tx, tobutin+tx, chloral candy+tx, betan+tx, pyridin-4-amine+tx, strychnine+tx, 1-hydroxy-1H-pyridin-2-thione+tx, 4- (quinoxalin-2-ylamino) benzenesulfonamide+tx, 8-hydroxyquinoline+tx, bronopol+tx, copper hydroxide+tx, cresol+tx, dipyryl+tx, sodium disulfonate+tx formaldehyde+tx, mercuric plus+tx, kasugamycin+tx, kasugamycin hydrochloride hydrate+tx, bis (dimethyldithiocarbamate) nickel+tx, trichloromethyl pyridine+tx, xin Saitong +tx, oxolinic acid+tx, terramycin+tx, hydroxyquinoline potassium sulfate+tx, thiabendazole+tx, streptomycin+tx, streptomycin sesquisulfate+tx, leaf blight+tx, thimerosal+tx, cotton brown moth gv+tx, agrobacterium radiobacter+tx, amblyseius species (Amblyseius spp.) +tx, apium noctuid npv+tx, primordica wing small bees (Anagrus atoms) +tx, short aphid small bees (Aphelinus abdominalis) +tx, cotton aphid parasitic bees (Aphidius colemani) +tx, aphid gall (Aphidoletes aphidimyza) +tx, alfalfa noctuid npv+tx, bacillus sphaericus+tx Beauveria bassiana (Beauveria brongniartii) +TX, common green sand fly (Chrysoperla carnea) +TX, latent ladybug (Cryptolaemus montrouzieri) +TX, codling moth GV+TX, siberian bombycis sibirica (Dacnus sibirica) +TX, pea potential She Yingji bee (Diglyphus isaea) +TX, aphis livida (Encarsia for mosa) +TX, aphis praecox (Eretmocerus eremicus) +TX, heterodera parvus (Heterorhabditis bacteriophora) and heterodera parvus (H.megdis) +TX, ladybug (Hippodamia convergens) +TX, orange powder parasitic wasp (Leptomastix dactylopii) +TX, lygus lucorum (Macrolophus caliginosus) +TX, cabbage moth NPV+TX, huang Kuobing small wasp (Metaphycus helvolus) +TX, yellow green muscardine (Metarhizium anisopliae) and acum) +TX Metarhizium anisopliae Microsporum variant (Metarhizium anisopliae var. Aniopliae) +TX, european new pine needle (Neodiprion sertifer) NPV and Red pine needle (N. Lecontei) NPV+TX, centipeda species+TX, paecilomyces fumosoroseus (Paecilomyces fumosoroseus) +TX, chile amblyseius (Phytoseiulus persimilis) +TX, mao Wen nematodes (Steinernema bibionis) +TX, plutella xylostella (Steinernema carpocapsae) +TX, spodoptera exigua+TX, grignard nematodes (Steinernema glaseri) +TX, sharpe nematodes (Steinernema riobrave) +TX, steinernema riobravis +TX, gryllotalpa nematodes (Steinernema scapterisci) +TX, spp+ TX, tricholoma spinosa (Steinenema spp.), trichocephalus species+TX, xiyaka spp+ TX, vernonis (Typhlodromus occidentalis) +, verticillium lecanii (Verticillium lecanii) +TX), azophos (apholate) +TX, bis (aziridine) methylaminophosphine sulfide (bisazir) +TX, busulfan+TX, dimatif (dimatif) +TX, hexamethylmelamine (hemel) +TX, hexamethylphosphoric (hempa) +TX, methylnasal discharge bar (meta) +TX, methylthionasal discharge bar (methiopa) +TX, methylphosphine (methyl apholate) +TX, infertility (morzid) +TX, fluorochlor (penfluron) +TX, nasal discharge bar (tepa) +TX, thiohexamethylphosphoric (thioboss) +TX, thionasal discharge bar+TX, tritamine+TX, imine+TX, (E) -dec-5-en-1-ylacetate and (E) -dec-5-en-1-ol+TX, (E) -tridec-4-en-1-ylacetate+TX, (E) -6-methyl-heptzine (methyl-apholate) +), and (Z) -hexadecen-1-4-yl acetate, (Z-4-hexadecen-1-4-yl acetate, Z-1-hexadecane-4-yl acetate (Z) -eicosa-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) -dodeca-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+TX, 14-methyl octadec-1-en+TX, 4-methyl nonan-5-ol and 4-methyl nonan-5-one+TX, alpha-multifin+TX, celastonite pheromone+TX, doddienol (codlemore) +TX, available monmons (codlemone) +tx, lureone (cuelum) +tx, epoxy nona TX, dodeca-8-dien-1-yl acetate+TX, dodecen-1-acetate+TX, 4-methyl octadec-1-en+TX, 4-methyl octa-5-ol and 4-methyl octadien-5-ol+TX, alpha-multifin+TX, alpha-multison, the trapping and killing alkene mixture IV+TX, hexaluring agent (hexalure) +TX, bark beetle dienol (ipsdienol) +TX, small panol (ipsenol) +TX, chafer sex attractant (jamilure) +TX, trimethyldioxacyclononane (linetin) +TX, litura+TX, noctuid sex attractant (looplus TX), trapping ester (midlure) +TX, megamoving acid+TX, methyl ether (methyl eugenol) +TX, trapene (mu scale) +TX, octadeca-2, 13-diene-1-yl acetate+TX, octadeca-3, 13-diene-1-yl acetate+TX, he Kangbi (orfral) TX, coconut-moth gold gatheren (oryc) +TX, TX, non-protuberance (osdie) +TX, methyl ether (methyl eugenol) +TX, insect-1-yl acetate+TX, octadeca-3, 13-diene-1-yl acetate+TX, he Kangbi (orfral) TX, coconut-moth-gold gatheren+TX, TX edible fungi methyl attractant alcohol (surcatol) +TX, tetradec-11-en-1-yl acetate+TX, mediterranean fly attractant (trimedilure) +TX, mediterranean fly attractant A+TX, mediterranean fly attractant B1+TX, mediterranean fly attractant B2+TX, mediterranean fly attractant C+TX, trunk-call+TX, 2- (octylthio) -ethanol+TX, mosquito repellent ketone (butopyronoxy) +TX, butoxy (polypropylene glycol) +TX, dibutyl adipate+TX, dibutyl phthalate+TX, dibutyl succinate+TX, mosquito repellent amine+TX, mosquito repellent (dimethyl carbate) +TX, dimethyl phthalate+TX, ethylhexyl glycol+TX, hexaurea (hexamide) +TX, mequindine (methoquin-butyl) +TX, methyl neodecanoamide (methaneodecanamide) +TX, oxamate) +TX, picarrhidine (picaridin) +TX, 1-dichloro-1-nitroethane+TX, 1-dichloro-2, 2-bis (4-ethylphenyl) ethane+TX, 1, 2-dichloropropane and 1, 3-dichloropropene+TX, 1-bromo-2-chloroethane+TX, 2-trichloro-1- (3, 4-dichlorophenyl) ethyl acetate+TX, 2-dichloroethylene 2-ethylsulfinylethyl methyl phosphate+TX, 2- (1, 3-dithiopentan-2-yl) phenyl dimethylcarbamate+TX 2- (2-Butoxyethoxy) ethyl thiocyanate+TX, 2- (4, 5-dimethyl-1, 3-dioxolan-2-yl) phenylmethylcarbamate+TX, 2- (4-chloro-3, 5-xylyloxy) ethanol+TX, 2-chlorovinyldiethyl phosphate+TX, 2-imidazolidinone+TX, 2-isovalerylindan-1, 3-dione+TX, 2-methyl (prop-2-ynyl) aminophenylmethylcarbamate+TX, 2-thiocyanoethyl laurate+TX, 3-bromo-1-chloropro-1-en+TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate+TX, 4-methyl (prop-2-ynyl) amino-3, 5-xylylmethyl carbamate+tx, 5-dimethyl-3-oxocyclohex-1-enyl dimethyl carbamate+tx, acephate+tx, acrylonitrile+tx, airy's agent+tx, alomicin+tx, carbofuran+tx, alpha-ecdysone+tx, aluminum phosphide+tx, carbofuran+tx, neonicotin+tx, ethylmethidathion (ath) +tx, picoline+tx, bacillus thuringiensis delta-endotoxin+tx, barium hexafluorosilicate+tx, barium polysulfide+tx, fumigating pyrethrin+tx, bayer 22/190+tx, bayer 22408+tx, beta-cyhalothrin+tx, pencythrin (biofanomethrin) +tx, biochlorethren+tx bis (2-chloroethyl) ether+tx, borax+tx, bromophenylphosphorus+tx, bromo-ddt+tx, methomyl+tx, benfuracarb+tx, termat (bustathiofos) +tx, butfurephos+tx, calcium arsenate+tx, calcium cyanide+tx, carbon disulfide+tx, carbon tetrachloride+tx, bardan hydrochloride+tx, sevidine (cervadine) +tx, borneol+tx, chlordan+tx, decachloroketone+tx, chloroform+tx, chloropicrin+tx, chlorpyrifos+tx, chlorpyrifos (chlorpyrifos) +tx, cis-benfurin (cis-resmethrin) +tx, cis-benfurin (cismethrin) +tx, fenthrin (clocritin) (alias TX, copper acetylarsenite+tx, copper arsenate+tx, copper oleate+tx, phospho (coumarate) +, cryolite+TX, CS 708+TX, benzonitrile phosphorus+TX, sulfolane+TX, cycloxaprine+TX, acephate+TX, d-tetramethrin+TX, DAEP+TX, dafone+TX, desmethylcarbofuran+TX, desmethylter (diamidafos) +TX, isochlorophosphorus+TX, desmphosphorus+TX, dicresyl+TX, cycloxaprine+TX, di-4-methylpyrazol-3-yl phosphate+TX asthma (dior) +TX, tetrafluoromethrin+TX, dimchip+TX, permethrin+TX, methylparaben+TX, dichlorvos+TX, prochlorperan+TX, penta-nitrophenol+TX, delpham+TX, benomyl+TX, vegetable phosphorus+TX, thiopyran phosphorus+TX, DSP+TX, ecdysterone+TX, EI 1642+TX, EMPC+TX, EPBP+TX, ethohos+TX, ethionine+TX, ethyl formate+TX dibromoethane+tx, dichloroethane+tx, ethylene oxide+tx, exd+tx, dermatophagoides+tx, ethylbenzene+tx, fenitrothion+tx, oxamidines (fenoxacrim) +tx, pyrifos+tx, fenitrothion+tx, ethylthiophos+tx, fluclobine (fludrofen) +tx, fenphos+tx, phosphoarsine+tx, butylcyclophos+tx, furwire+tx, anti-vermin+tx, biguanide octoate+tx, tetrathia sodium carbonate+tx, fenitrox (halfenprox) +tx, hch+tx, heod+tx, heptachloro+tx, speed sulfenphos+tx, hh+tx, hydrogen cyanide+tx, quinoline+tx, ipsp+tx, chlorazol+tx, isocarbophos+tx, isotonian+tx, iso Liu Lin +tx, transplanting panoxadol+tx, ipsilan+tx, oxadol+tx, juvenile molluscum+i Juvenile hormone II+TX, juvenile hormone III+TX, chlorovaleric+TX, methoprene+TX, lead arsenate+TX, bromophenyl+TX, acetamiprid+TX, thiazolephosphine+TX, m-isopropylphenyl methyl carbamate+TX, magnesium phosphide+TX, azido+TX, methylparaben+TX, aphis-p-m, aphethion+TX, mercurous chloride+TX, methiphos+TX, metam+TX, metam potassium salt+TX, metam sodium salt+TX, methylsulfonyl fluoride+TX, butenyl phosphorus+TX, methoprene+TX, methyl isothiocyanate+TX, methyl chloroform+TX, methylene chloride+TX, oxatrunk+TX, methoprene+TX, naphthalene+TX, naproxen+TX, nicotine+TX, nicotine sulfate+TX, nitrothiazine+TX, orthotx, O-5-dichloro-4-iodophenyl-O-ethyl-thiophanate+O, O-diethyl O-4-methyl-2-oxo-2H-benzopyran-7-yl thiophosphonate +TX, O, O-diethyl O-6-methyl-2-propylpyrimidin-4-yl thiophosphonate +TX, O, O, O ', O' -tetrapropyldithiopyrophosphonate +TX, oleic acid +TX, p-dichlorobenzene +TX, methyl parathion +TX, pentachlorophenol +TX, pentachlorophenyl laurate +TX, PH 60-38+TX, fenphos +TX, p-chlorphos +TX, phosphine +TX, methyl octaphos +TX, methamidophos +TX, polychlorinated dicyclopentadiene isomer +TX, potassium arsenite +TX, potassium thiocyanate +TX, precocin i+tx, precocin ii+tx, precocin iii+tx, amidpyrifos+tx, profenothrin+tx, methomyl+tx, profenofos+tx, pyrifos+tx, tetramethrin+tx, quassia extract (quassia) +tx, quetiapine-methyl+tx, tranin+tx, iodosal+tx, benfurthrin+tx, rotenone+tx, thianthrene+tx, ryn+tx, rimidine+tx, rimoridine+tx, sabadilla (sabadilla) +tx, octamethiphos+tx, kewire+tx, SI-0009+tx, thiopropion+tx, sodium arsenite+tx, sodium cyanide+tx, sodium fluoride+tx, sodium hexafluoride+tx, sodium pentachlorophenate+tx, sodium selenate+tx, sodium sulfox (suuron) +tx, sodium sulfoxalone+sodium (sufon-sodium, sodium sulfox+sodium sulfopropyl+sulfur, sodium and sodium sulfide+propylphosphine+tx; tar+tx, thiamethoxam+tx, tde+tx, butylpyrimidyl-p+tx, dithiophosphate+tx, cycloprothrin+tx, tetrachloroethane+tx, thiacloprid+tx, thiocyclam+tx, thiocyclam+oxalate+tx, tebufos+tx, monosultap+tx, monocodium+tx, tetrabromothrin+tx, antichlorethrin+tx, triazamate+tx, isoparaffin-3 (trichloretho-3) +tx, toxaphos+tx, mixed carboxin+tx, triflumuron carboxin (tolprocarb) +tx, chlorpyrifos+tx, nitenpyram+tx, veratrin+tx, XMC+tx, zeta-cypermethrin (tatametin) +tx, zinc phosphide+tx, triad+tx, tebufenpyrad+tx, tetramethrin+tx, bis (t+tin) oxide+acetamide, bromoxycarb+tx, ferric phosphate +TX, niclosamide-ethanolamine +TX, tributyltin oxide +TX, pyrimorph +TX, snail +TX, 1, 2-dibromo-3-chloropropane +TX, 1, 3-dichloropropene +TX, 3, 4-dichlorotetrahydrothiophene 1, 1-dioxide +TX, 3- (4-chlorophenyl) -5-methyl-rhodamine +TX, 5-methyl-6-thio-1, 3, 5-thiadiazin-3-ylacetic acid +TX 6-Isopentenylaminopurine+TX, fluoxadenine+TX, benzothiadiaz+TX, cytokinin+TX, DCIP+TX, furfural+TX, isoamidofos+TX, kinetin+TX, verticillium composition +TX, tetrachlorothiophene+TX, xylenol+TX, zeatin+TX, potassium Ethyl xanthate+TX Arecarboxylic acid benzene+TX, arecarboxylic acid benzene-S-methyl+TX, giant knotweed (Reynoutria sachalinensis) extract+TX, alpha-chlorohydrin+TX, antuol+TX, barium carbonate+TX, bismurine urea+TX, bromomurine protuberance+TX, bromodiuron+TX, bromomurine amine+TX, chloromurine ketone+TX, cholecalciferol+TX, chlorowarrior+TX, clomefloc+TX, mousetrap+TX, thiabendan+TX, diphacin+TX, calciferol+TX, flunix+TX, fluoroacetamide+TX, flunix+TX, flunix hydrochloride+TX, raticide+TX, praziridine+TX, praziquantel+TX, ponin+TX, sodium fluoroacetate+TX, thallium sulfate+TX, mous+TX, mousetrap+TX, flunix, flunix+TX, and flunix+TX, 2- (-2-butoxyethoxy) ethyl piperonate+tx, 5- (1, 3-benzodioxol-5-yl) -3-hexylcyclohex-2-enone+tx, farnesol with nerolidol+tx, synergistic propargyl ether+tx, MGK 264+tx, synergistic ether+tx, synergistic aldehyde+tx, synergistic ester (propylene isomer) +tx, S421+tx, synergistic powder+tx, sesamin (sesamolin) +tx, sulfoxide+tx, anthraquinone+tx, copper naphthenate+tx, king copper+tx, dicyclopentadiene+tx, sialon+tx, zinc naphthenate+tx, fomerzine+tx, clothes Ma Ning +tx, ribavirin+tx, chloroindyl (chloroindazede) +tx, mercuric oxide+tx, methyl tolin+tx, azaconazole+tx, biphenyl triazolol+tx, myclobutan+tx, cyproconazole+tx; difenoconazole+tx, diniconazole+tx, epoxiconazole+tx, fenbuconazole+tx, fluquinconazole+tx, flusilazole+tx, flutriazole+tx, furazamine+tx, hexaconazole+tx, imazalil+tx, imibenconazole+tx, ipconazole+tx, metconazole+tx, myclobutanil+tx, paclobutrazol+tx, fenoxanil+tx, penconazole+tx, prothioconazole+tx, pyriftime (pyrifenox) +tx, prochloraz+tx, propiconazole+tx, pyribenzoxazole+tx, simeconazole (simeconazole) +tx, tebuconazole+tx, furazolol+tx, triazolone+tx, triadimenol+tx, triflumidine+tx, pyrimidol+tx, chlorpyrimidol+tx, fluben+tx, bupirimate+tx, methimazole (dimethirimol) +, ethiprole (ethirimol) +tx, dodemone+tx, fenpropidin (fenpropidin) +tx, fenpropimorph+tx, spiroxamine+tx, tridemorph+tx, cyprodinil+tx, pyrimethanil (pyrimethanil) +tx; fenpiclonil+tx, fludioxonil+tx, benalaxyl (benalaxyl) +tx, furalaxyl (furalaxyl) +tx, metalaxyl+tx, R-metalaxyl+tx; furamide+tx; oxadixyl (oxadixyl) +TX, carbendazim+TX, prochloraz (debacarb) +TX, fuberiberine+TX, thiabendazole+TX, ethiprole (chlorazolinate) +TX, sclerotinia (dichlozoline) +TX, methicillin (myclozoline) +TX, procymidone (procymidone) +TX, vinylrhizoline (vinclozoline) +TX, boscalid (boscalid) +TX, carboxin+TX, furamide+TX, fluoroamide (flutolanil) +TX, fenhexamine+TX, carboxin+TX, pyrimethanil+TX, pyrithiozamide (thiopyr) +TX, thifluzamide+TX, multi-fruit+TX, biguanidine+TX, azoxystrobin+TX, myclobutramine+TX, enoximide (englobutramine) +TX, glifloxazole+TX, fluoxamid+TX, trifloxystrobin+TX, trifloxystrobin+trifloxystrobin+TX; the trifloxystrobin + TX, picoxystrobin + TX, pyraclostrobin + TX, thiram + TX, mancozeb + TX, metiram + TX, methyscozin + TX, zineb + TX, captan + TX, furazolium + TX, folpet + TX, paramethazine + TX, poldoc-mixture + TX, copper oxide + TX, mancozeb + TX, quinolinium + TX, phthalazinam + TX, kewensan + TX, iprobenfos + TX, clomiphos + TX, methyl-ricketphos + TX, dichlormid + TX, bentazon-S + TX, difenoconazole (triclopyr-TX), chlorfluanid + TX, cyantran + TX, cyclo Ding Fulun + TX, dicyclanil (dicyclanil) +cyantranet Pyridazinone (dicyclomazone) +TX, chloronitramine (dicyclocan) +TX, diethofencarb (diethofencarb) +TX, dimethomorph+TX, flumorph+TX, dithianon (dithianon) +TX, ethaboxam (ethaboxam) +TX, ethaboxam (ethidiazole) +TX, famoxadone+TX, imidazolone (fenamidone) +TX, fenoxanil (fenxanil) +TX, azoxystrobin (ferimzone) +TX, fluazinam (fluazinam) +TX, flusulfamone+TX, flupyrazamide (flupyralide) +TX, flupyralide (flupyralide) +TX, flupyralide+TX, cycloxamide+TX, triethylphosphazene (semi-alium) +TX, oxamycin (fenmzol) + Sulfofibrium (methicillin) +TX, benomyl+TX, pencycuron (pencycuron) +TX, phthalide+TX, polyoxin (polyoxin) +TX, propamocarb (propamocarb) +TX, piroxicam+TX, iodofluazlactone (proquinazid) +TX, fluquindox (pyroquin) +TX, benzofuranone (pyriofenone) +TX, quinoxyfen+TX, pentachloronitrobenzene+TX, thiazoxam+TX, imidazolone (triazoxide) +TX, tricyclozole+TX, oxazinin+TX, validamycin+TX, valienamine+TX, zoxamide (zoxamide) +TX, manx, fluazyl (pyrifluazam) +TX, fluazyl (benzoxamide) +TX, benzoxazole+benzofuranone+TX, fluazyl+benzoxam, fluoxazoxamide +TX, 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (3 ',4',5' -trifluoro-biphenyl-2-yl) -amide +TX, isofluosmamide (isoflucypram) +TX, isothiazamide +TX, dimetidine (dipyridyl) +TX, 6-ethyl-5, 7-dioxo-pyrrolo [4,5] [1,4] dithianon [1,2-c ] isothiazole-3-carbonitrile +TX, 2- (difluoromethyl) -N- [ 3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide +TX, 4- (2, 6-difluorophenyl) -6-methyl-5-phenyl-pyridazin-3-carbonitrile +TX, (R) -3- (difluoromethyl) -1-methyl-N- [1, 3-trimethylindan-4-yl ] pyrazole-4-carboxamide +TX, 4- (2-bromo-1, 2-c ] isothiazol-3-carbonitrile +TX, 2- (difluoromethyl) -N- [ 3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide +TX, 4- (difluoromethyl) -N- (2, 6-difluorophenyl) -6-methyl-5-phenyl-pyridazin-3-carbonitrile +TX, R) -3- (difluoromethyl) -1-methyl-N-carbonium +TX penoxsulam+TX, azoxystrobin (jiaxiangjunzhi) +TX, rituximab (lvben mixin) +TX, dichlorobenzothiazole (dichlobrazox) +TX, mandersbin (manderstrobin) +TX, 3- (4, 4-difluoro-3, 4-dihydro-3, 3-dimethylisoquinolin-1-yl) quinolone+TX, 2- [ 2-fluoro-6- [ (8-fluoro-2-methyl-3-quinolinyl) oxy ] phenyl ] propan-2-ol+TX, thiapiprazole (oxathiapiprolin) +TX N- [6- [ [ [ (1-methyltetrazol-5-yl) -phenyl-methylene ] amino ] oxymethyl ] -2-pyridinyl ] carbamic acid tert-butyl ester+TX, bixafen (pyraziflumid) +TX, indenopyrazam (inpyrfluxam) + TX, trolprocarb +TX, halofop-razole+TX, isotrifluoracer-zole) +TX, 2- (difluoromethyl) -N- [ (3R) -3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide+TX, N' - (2, 5-dimethyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine+TX, N' - [4- (4, 5-dichlorothiazol-2-yl) oxy-2, 5-dimethyl-phenyl ] -N-ethyl-N-methyl-formamidine +TX, [2- [3- [2- [3, 5-bis (difluoromethyl) pyrazol-1-yl ] acetyl ] -4-piperidinyl ] thiazol-4-yl ] -4, 5-dihydroisoxazol-5-yl ] -3-chloro-phenyl ] methanesulfonate +TX, N- [6 [ (Z) - [ (1-methyltetrazol-5-yl) -phenyl-methylene ] amino ] oxymethyl ] -2-pyridinyl ] carbamic acid but-3-ynyl ester +TX methyl N- [ [5- [4- (2, 4-dimethylphenyl) triazol-2-yl ] -2-methyl-phenyl ] methyl ] carbamate+TX, 3-chloro-6-methyl-5-phenyl-4- (2, 4, 6-trifluorophenyl) pyridazin+TX, fluorobenzylpyridazine (pyridamethyl) +TX, 3- (difluoromethyl) -1-methyl-N- [1, 3-trimethylindan-4-yl ] pyrazole-4-carboxamide+TX, 1- [2- [ [1- (4-chlorophenyl) pyrazol-3-yl ] oxymethyl ] -3-methyl-phenyl ] -4-methyl-tetrazol-5-one+TX, 1-methyl-4- [ 3-methyl-2- [ [ 2-methyl-4- (3, 4, 5-trimethylpyrazol-1-yl) phenoxy ] methyl ] phenyl ] tetrazol-5-one+TX, aminopyramid (amipyrifen) +TX, flumetsulam+TX, indazole sulbactam+TX, fluxazoxamine+TX, (Z, 2E) -5- [1- (4-chlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamine+TX, picolinamide+TX, topiramate (fenpyroxamid) +TX, picolinamide+TX, iso Ding Yiyang quinoline+TX, isopropaquin+TX, fluquindoxy+TX, 1- [4- (2-chlorophenyl) -pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-methyl-5- [5- (4-chlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-enamid+TX, picolinamide+TX, and (2-methyl) 2- [ [4- (3-chlorophenyl) pyrazol-3-methyl ] pyrazol-3-yl ] oxy-methyl ] 5-one (which is described in the method of 60-methyl-3-methyl-ethyl-methyl- [ ], methyl 1- [ [4- [ (Z) -2-ethoxy-3, 3-trifluoro-prop-1-enoxy ] phenyl ] methyl ] pyrazole-3-carboxylate+tx (which may be prepared by the method described in WO 2020/056090), methyl N- [ [4- [1- (4-cyclopropyl-2, 6-difluoro-phenyl) pyrazol-4-yl ] -2-methyl-phenyl ] methyl ] carbamate+tx (which may be prepared by the method described in WO 2020/097012), methyl N- [4- [1- (2, 6-difluoro-4-isopropyl-phenyl) pyrazol-4-yl ] -2-methyl-phenyl ] methyl ] carbamate+tx (which may be prepared by the method described in WO 2020/097012), 6-chloro-3- (3-cyclopropyl-2-fluoro-phenoxy) -N- [2- (2, 4-dimethylphenyl) -2, 2-difluoro-ethyl ] -5-methyl-pyridazin-4-carboxamide+tx (which may be prepared by the method described in WO 2020/109391), 6-chloro-N- [2- (2-chloro-4-methyl-phenyl) -2, 2-difluoro-ethyl ] -3- (3-cyclopropyl-2-fluoro-phenoxy) -5-methyl-pyridazine-4-carboxamide +TX (which may be prepared by the method described in WO 2020/109391), 6-chloro-3- (3-cyclopropyl-2-fluoro-phenoxy) -N- [2- (3, 4-dimethylphenyl) -2, 2-difluoro-ethyl ] -5-methyl-pyridazine-4-carboxamide +TX (which may be prepared by the method described in WO 2020/109391). N- [2- [2, 4-dichloro-phenoxy ] phenyl ] -3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide +TX, N- [2- [ 2-chloro-4- (trifluoromethyl) phenoxy ] phenyl ] -3- (difluoromethyl) -1-methyl-pyrazole-4-carboxamide +TX, benthiavalicarb-isopropyl +TX, cyanophenyl +TX, 5-amino-1, 3, 4-thiadiazole-2-thiol zinc salt (2:1) +TX, fluopyram +TX, flufenoxadifam +TX, fluoxastrobin +TX, fluoroether-carboxamide +TX, pyriproxyfen (pyraproyne) +TX Piperazone (picrbutetrazox) +tx, 2- (difluoromethyl) -N- (3-ethyl-1, 1-dimethyl-indan-4-yl) pyridine-3-carboxamide+tx, 2- (difluoromethyl) -N- ((3R) -1, 3-trimethylindan-4-yl) pyridine-3-carboxamide+tx, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile+tx, methyltetraproline (methyltetrapro-le) +tx 2- (difluoromethyl) -N- ((3R) -1, 3-trimethylindan-4-yl) pyridine-3-carboxamide +TX, alpha- (1, 1-dimethylethyl) -alpha- [4'- (trifluoromethoxy) [1,1' -biphenyl ] -4-yl ] -5-pyrimidinyl methanol +TX, fluoro Sha Puluo forest (fluxaapipin) +TX, enoximide (enoxastrobin) +TX, (Z) -3-methoxy-2- [ 2-methyl-5- [4- (trifluoromethyl) triazol-2-yl ] phenoxy ] prop-2-enoic acid methyl ester +TX, methyl (Z) -3-methoxy-2- [ 2-methyl-5- (4-propyltriazol-2-yl) phenoxy ] prop-2-enoate +TX, (Z) -2- [5- (3-isopropylpyrazol-1-yl) -2-methyl-phenoxy ] -3-methoxy-prop-2-enoate +TX, (Z) -3-methoxy-2- [ 2-methyl-5- (3-propylpyrazol-1-yl) phenoxy ] prop-2-enoate +TX, (Z) -3-methoxy-2- [ 2-methyl-5- [3- (trifluoromethyl) pyrazol-1-yl ] phenoxy ] prop-2-enoate +TX (these compounds can be prepared by the methods described in WO 2020/079111), (Z) -2- (5-cyclohexyl-2-methyl-phenoxy) -3-methoxy-prop-2-enoate +TX, (Z) -2- (5-cyclopentyl-2-methyl-phenoxy) -3-methoxy-prop-2-enoate +TX (these compounds can be prepared by the methods described in WO 2020/387, such compounds can be prepared by the methods described in WO 2020/193387), 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile+tx, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (5-sulfanyl-1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile+tx, 4- [ [6- [2- (2, 4-difluorophenyl) -1, 1-difluoro-2-hydroxy-3- (5-thio-4H-1, 2, 4-triazol-1-yl) propyl ] -3-pyridinyl ] oxy ] benzonitrile+tx, trinitron+tx, mesogenic agent+tx, thiabendazole+tx, al Mi Tuolin (amectin) +, iprodione+tx, octone (octocrylene) +; n ' - [ 5-bromo-2-methyl-6- [ (1S) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine +tx, N ' - [ 5-bromo-2-methyl-6- [ (1R) -1-methyl-2-propoxy-ethoxy ] -3-pyridinyl ] -N-ethyl-N-methyl-formamidine +tx, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine +tx, N ' - [ 5-chloro-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine +tx, N ' - [ 5-bromo-2-methyl-6- (1-methyl-2-propoxy-ethoxy) -3-pyridinyl ] -N-isopropyl-N-methyl-formamidine +tx (these compounds may be prepared by the method described in WO 2015; n' - [ 5-bromo-2-methyl-6- (2-propoxypropoxy) -3-pyridinyl ] -N-ethyl-N-methyl-formamidine+tx (this compound may be prepared by the method described in IPCOM 000249876D); N-isopropyl-N '- [ 5-methoxy-2-methyl-4- (2, 2-trifluoro-1-hydroxy-1-phenyl-ethyl) phenyl ] -N-methyl-formamidine +tx, N' - [4- (1-cyclopropyl-2, 2-trifluoro-1-hydroxy-ethyl) -5-methoxy-2-methyl-phenyl ] -N-isopropyl-N-methyl-formamidine +tx (these compounds may be prepared by the methods described in WO 2018/228896); N-ethyl-N '- [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) oxetan-2-yl ] phenyl ] -N-methyl-formamidine +tx, N-ethyl-N' - [ 5-methoxy-2-methyl-4- [ (2-trifluoromethyl) tetrahydrofuran-2-yl ] phenyl ] -N-methyl-formamidine +tx (these compounds may be prepared by the methods described in WO 2019/110427); n- [ (1R) -1-benzyl-3-chloro-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- [ (1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- [ (1R) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- [ (1S) -1-benzyl-3, 3-trifluoro-1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide + TX, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide + TX, 8-fluoro-N- [ (1R) -1-methyl-propyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- [ (1R) -1-methyl-3-methyl ] -8-fluoro-3-carboxamide + TX, N- [ (1R) -1-dimethyl-butyl ] -7, 8-difluoro-quinoline-3-carboxamide + TX, N- [ (1S) -1-benzyl-methyl-3-carboxamide } -, 8-fluoro-N- [ (1S) -1- [ (3-fluorophenyl) methyl ] -1, 3-dimethyl-butyl ] quinoline-3-carboxamide + TX, N- [ (1R) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- [ (1S) -1-benzyl-1, 3-dimethyl-butyl ] -8-fluoro-quinoline-3-carboxamide + TX, N- ((1R) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide + TX, N- ((1S) -1-benzyl-3-chloro-1-methyl-but-3-enyl) -8-fluoro-quinoline-3-carboxamide + TX (these compounds may be prepared by the methods described in WO 2017/153380); 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline + TX, 1- (6, 7-dimethylpyrazolo [1,5-a ] pyridin-3-yl) -4, 6-trifluoro-3, 3-dimethyl-isoquinoline + TX, 4-difluoro-3, 3-dimethyl-1- (6-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline + TX, 4-difluoro-3, 3-dimethyl-1- (7-methylpyrazolo [1,5-a ] pyridin-3-yl) isoquinoline + TX, 1- (6-chloro-7-methyl-pyrazolo [1,5-a ] pyridin-3-yl) -4, 4-difluoro-3-dimethyl-isoquinoline + TX (these compounds may be prepared by the methods described in WO 2017/025510); 1- (4, 5-dimethylbenzimidazol-1-yl) -4, 5-trifluoro-3, 3-dimethyl-isoquinoline + TX, 1- (4, 5-dimethylbenzimidazol-1-yl) -4, 4-difluoro-3, 3-dimethyl-isoquinoline + TX, 6-chloro-4, 4-difluoro-3, 3-dimethyl-1- (4-methylbenzimidazol-1-yl) isoquinoline + TX, 4-difluoro-1- (5-fluoro-4-methyl-benzoimidazol-1-yl) -3, 3-dimethyl-isoquinoline + TX, 3- (4, 4-difluoro-3, 3-dimethyl-1-isoquinolyl) -7, 8-dihydro-6H-cyclopenta [ e ] benzimidazole + TX (these compounds may be prepared by the methods described in WO 2016/156085); N-methoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] cyclopropanecarboxamide+TX, N, 2-dimethoxy-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] carboxamide+TX, N-ethyl-2-methyl-N- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] carboxamide+TX, 1-methoxy-3-methyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea+TX, 1, 3-dimethoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea+TX, 3-ethyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] urea+TX, 1-methoxy-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] carboxamide+TX, 1-methoxy-3- [ [4- [5- (trifluoromethyl) -3-methyl ] phenyl ] methyl ] carbamide 4, 4-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one+tx, 5-dimethyl-2- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] isoxazolidin-3-one+tx, 1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] pyrazole-4-carboxylic acid ethyl ester+tx, N-dimethyl-1- [ [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methyl ] -1,2, 4-triazol-3-amine+tx. The compounds in this paragraph can be prepared by the methods described in WO 2017/055473, WO 2017/055469, WO 2017/093348 and WO 2017/118689; 2- [6- (4-chlorophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol+tx (this compound may be prepared by the method described in WO 2017/029179); 2- [6- (4-bromophenoxy) -2- (trifluoromethyl) -3-pyridinyl ] -1- (1, 2, 4-triazol-1-yl) propan-2-ol+tx (this compound may be prepared by the method described in WO 2017/029179); 3- [2- (1-chlorocyclopropyl) -3- (2-fluorophenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile +tx (this compound may be prepared by the methods described in WO 2016/156290); 3- [2- (1-chlorocyclopropyl) -3- (3-chloro-2-fluoro-phenyl) -2-hydroxy-propyl ] imidazole-4-carbonitrile +tx (this compound may be prepared by the method described in WO 2016/156290); 2-amino-6-methyl-pyridine-3-carboxylic acid (4-phenoxyphenyl) methyl ester+tx (this compound may be prepared by the method described in WO 2014/006945); 2, 6-dimethyl-1H, 5H- [1,4] dithiino [2,3-c:5,6-c' ] bipyrrolidinyl-1, 3,5,7 (2H, 6H) -tetraone+TX (this compound can be prepared by the process described in WO 2011/138281); n-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] thiobenzamide+tx; n-methyl-4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide + TX; (Z, 2E) -5- [1- (2, 4-dichlorophenyl) pyrazol-3-yl ] oxy-2-methoxyimino-N, 3-dimethyl-pent-3-enamine+tx (this compound can be prepared by the method described in WO 2018/153707); n' - (2-chloro-5-methyl-4-phenoxy-phenyl) -N-ethyl-N-methyl-formamidine+tx; n' - [ 2-chloro-4- (2-fluorophenoxy) -5-methyl-phenyl ] -N-ethyl-N-methyl-formamidine+tx (this compound may be prepared by the method described in WO 2016/202742); 2- (difluoromethyl) -N- [ (3S) -3-ethyl-1, 1-dimethyl-indan-4-yl ] pyridine-3-carboxamide + TX (this compound can be prepared by the method described in WO 2014/095675); (5-methyl-2-pyridinyl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone+tx, (3-methylisoxazol-5-yl) - [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] methanone+tx (these compounds may be prepared by the methods described in WO 2017/220485); 2-oxo-N-propyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide+tx (this compound can be prepared by the method described in WO 2018/065414); 1- [ [5- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] -2-thienyl ] methyl ] pyrazole-4-carboxylic acid ethyl ester+tx (this compound can be prepared by the method described in WO 2018/158365); 2, 2-difluoro-N-methyl-2- [4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] phenyl ] acetamide+tx, N- [ (E) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide+tx, N- [ (Z) -methoxyiminomethyl ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide+tx, N- [ N-methoxy-C-methyl-carbo-imino ] -4- [5- (trifluoromethyl) -1,2, 4-oxadiazol-3-yl ] benzamide+tx (these compounds may be prepared by the methods described in WO 2018/202428);

Microorganisms, these microorganisms include: acinetobacter reuteri+TX, acremonium+TX, cephalosporium+TX+TX, acremonium kaki (Acremonium diospyri) +TX, acremonium echinococci (Acremonium obclavatum) +TX, philippine moth granulosis virus (AdoxGV)+TX, agrobacterium radiobacter strain K84+TX, chain latticeSpore bacteria+TX, alternaria obtusifolia+TX, alternaria destructor (Alternaria destruens)+TX, powdery mildew parasitic spore->+TX, aspergillus flavus AF 36->+TX, aspergillus flavus NRRL 21882 +.>+TX, aspergillus species+TX, aureobasidium pullulans+TX, azospirillum+TX, (-A.sub.)>+TX、TAZO/>) +TX, azotobacter+TX, azotobacter chroococcus (Azotobacter chroocuccum)/(N.fuscosum)>+TX, azotobacter aschersonia (Bionatural Blooming->) +TX, bacillus amyloliquefaciens+TX, bacillus cereus+TX, bacillus chitin-eroding strain (Bacillus chitinosporus strain) CM-1+TX, bacillus chitin-eroding strain (Bacillus chitinosporus strain) AQ746+TX, bacillus licheniformis strain HB-2 (BiostartTM ]>) +TX, bacillus licheniformis strain 3086 (+.>+TX、Green) +TX, bacillus circulans+TX, bacillus firmus (++>+TX、/>+TX、) +TX, bacillus firmus strain I-1582+TX, bacillus macerans+TX, bacillus dead sea (Bacillus marismortui) +TX, bacillus megaterium+TX, bacillus mycoides strain AQ726+TX, bacillus masti (Milky Spore depicting) >) +TX, bacillus pumilus species+TX, bacillus pumilus strain GB34 (Yield) +TX, bacillus pumilus strain AQ717+TX, bacillus pumilus strain QST 2808 (-)>+TX、Ballad/>) +TX, bacillus sphaericus (Bacillus spahericus)/(T.sp.)>+TX, bacillus species+TX, bacillus strain AQ175+TX, bacillus strain AQ177+TX, bacillus strain AQ178+TX, bacillus strain QST 713 (the genus Bacillus)>+TX、/>+TX、/>) +TX, bacillus subtilis strain QST 714 +.>+TX, bacillus subtilis strain AQ153+TX, bacillus subtilis strain AQ743+TX, bacillus subtilis strain QST3002+TX Bacillus subtilis strain QST3004+TX, bacillus amyloliquefaciens variant strain FZB24 (-)>+TX、/>) +TX, bacillus thuringiensis Cry 2Ae+TX, bacillus thuringiensis Cry1Ab+TX, bacillus thuringiensis catze (Bacillus thuringiensis aizawai) GC 91+TX, bacillus thuringiensis israel (Bacillus thuringiensis israelensis) (+TX、/>+TX、/>) +TX, bacillus thuringiensis Coulter (Bacillus thuringiensis kurstaki) (-A.sub.f.)>+TX、/>+TX、/>+TX、+TX、Scutella/>+TX、Turilav/>+TX、/>+TX、Dipel/>+TX、+TX、/>) +TX, bacillus thuringiensis Coulter BMP 123 +.>+TX, bacillus thuringiensis Coulter HD-1 +.>+TX, bacillus thuringiensis strain BD#32+TX, bacillus thuringiensis strain AQ52+TX, bacillus thuringiensis catze variety (Bacillus thuringiensis var. Aizawai) ("A) >+TX、/>) +TX, bacterial species (bacterial spp.)+TX、/>+TX、/>) +TX, corynebacterium michigan (Clavipacter michiganensis) phage +.>+TX、/>+TX, beauveria bassiana @+TX、Brocaril/>) +TX, beauveria bassiana GHA (Mycotrol +.>+TX、Mycotrol/>+TX、/>) +TX, beauveria bassiana (Beauveria brongniartii) (-A.brucei)>+TX、Schweizer/>+TX、/>) +TX, beauveria spp.) +TX, botrytis cinerea) +TX, soybean slow-growing rhizobia (Bradyrhizobium japonicum)+TX, bacillus pumilus (Brevibacillus brevis) +TX, bacillus thuringiensis, walking-aid (Bacillus thuringiensis tenebrionis)/(P.sp)>+TX, btBooster+TX, burkholderia cepacia (Burkholderia cepacia) (-A.cepacia)>+TX、/>+TX、Blue/>) +TX, burkholderia (Burkholderia gladii) +TX, burkholderia gladioli (Burkholderia gladioli) +TX, burkholderia species (Burkholderia spp.) +TX, canada fungus (Canadian thistle fungus) (CBH Canadian)>) +TX, candida casei (Candida butyl) +TX, candida famata) +TX, candida frame+TX, candida glabrata) +TX, candida Jijohnsonensis (Candida guilliermondii) +TX, candida kochia (Candida melibiosica) +TX, candida olive (Candida oleophila) strain O+TX, candida parapsilosis (Candida parapsilosis) +TX, candida membrana (Candida pelliculosa) +TX, rhodotorula iron (Candida pulcherrima) +TX, candida ruit (Candida reukaufii) +TX, and Candida zizaniae ((G) >+TX、/>) +TX, candida sake (Candida sake) +TX, candidaGenus species (Candida spp.) + TX, candida gracilis (Candida tenius) +tx, sildencia dessicans (cedea dravisae) +tx, xanthomonas chrysogena (Cellulomonas flavigena) +tx, spirochaeta shell (Chaetomium cochliodes)+TX, chaetomium globosum (Chaetomium globosum)/(N.globosum)>+TX, purple bacillus (Chromobacterium subtsugae) iron-yew strain PRAA4-1T ∈>+TX, cladosporium (Cladosporium cladosporioides) +TX, cladosporium (Cladosporium oxysporum) +TX, cladosporium viridis (Cladosporium chlorocephalum) +TX, cladosporium species (Cladosporium spp.) +TX, cladosporium superfine (Cladosporium tenuissimum) +TX, scopularium roseum (Clonostachys rosea) and Scopularium roseum>+TX, anthrax aculeatus (Colletotrichum acutatum) +TX, coniothyrium minitans (Coniothyrium minitans) (Cotans +)>) +TX, coniothyrium spp, +TX, cryptococcus albus (Cryptococcus albidus)/(I/O)>+TX, cryptococcus terranei (Cryptococcus humicola) +TX, cryptococcus infirmitis-miniatus+TX, cryptococcus laurentii (Cryptococcus laurentii) +TX, malus pumila particle virus (Cryptophlebia leucotreta granulovirus)/(35) >+TX, copper kepengzhen (Cupriavidus campinensis) +TX, codling moth granulovirus (Cydia pomonella granulovirus)>+TX, codling moth granulosis virus (+.>+TX、Madex/>+TX、Madex Max//>) +TX, light pillar (Cylindrobasidium laeve)/(x)>+TX, cladosporium (Cylindrocaladium) +TX, debaryomyces hansenii (Debaryomyces hansenii) +TX, debaryomyces hawaii (Drechslera hawaiinensis) +TX, enterobacter cloacae (Enterobacter cloacae) +TX, enterobacteriaceae (Enterobacteriaceae) +TX, and Aureobasidium (Entomophtora virulenta) or the like>+TX, epicoccum nigrum) +TX, epicoccum nigrum Epicoccum purpurascens) +TX, epicoccum species+TX, filamentous Bacillus (Filobasidium floriforme) +TX, fusarium acuminatum+TX, fusarium oxysporum+TX, fusarium oxysporum->+TX, fusarium+TX, fusarium species +TX, geotrichum candidum (Galactomyces geotrichum) +TX, scolopendra (Gliocladium catenulatum) (-A.tenuifolia)>+TX、/>) +TX, gliocladium roseum (Gliocladium roseum) +TX, gliocladium species +.>+TX, scolopendra viridis->+TX, granulosis virus->+TX, halophilous bacillus (Halobacillus halophilus) +TX, halophilous bacillus (Halobacillus litoralis) +TX, halophilous bacillus (Halobacillus trueperi) +TX, halophilous species +TX, halophilous monad (Halomonas subglaciescola) +TX, vibrio variabilis (Halovibrio variabilis) +TX, hansenula polymorpha +TX, cotton bollworm nuclear polyhedrosis virus- >+TX, heliothis sitophila nuclear polyhedrosis virus ++>+TX, isoflavone-formononetin->+TX, klebsiella lemon+TX, klebsiella species+TX, dactylicapnos (Lagenidium giganteum)/(Tx)>+TX, lecanicillium longiforme (Lecanicillium longisporum)>+TX, gecko scabies (Lecanicillium muscarium)>+TX, lymantria dispar nuclear polyhedrosis virus ++>+TX, haemophilus+TX, grignard Mei Lajun (Meira gell)akoniglii) +tx, destruxin->+TX, metarhizium anisopliae (Destruxin->)+TX、Metschnikowia fruticola/>+TX, mei Ji Yeast (Metschnikowia pulcherrima) +TX, microaschersonia (Microdochium dimerum)/(X)>+TX, micromonospora coelicolor (Micromonospora coerulea) +TX, haematococcus (Microsphaeropsis ochracea) +TX, malodorous white fungus 620+TX, roses malodorous fungus strain A3-5+TX, mycorrhiza species (mycorhizae spp.) (-)+TX、Root/>) +TX, veratri-Veratri strain AARC-0255->+TX、BROS+TX, ophiostoma piliferum strain D97->+TX, paecilomyces farinosa (Paecilomyces farinosus) +TX, paecilomyces fumosoroseus (++)>+TX、/>) +TX, paecilomyces lilacinus (Paecilomyces linacinus) (Biostat>) +TX, paecilomyces lilacinus strain 251 (MeloCon +.>) +TX, paenibacillus polymyxa+TX, pantoea agglomerans (Blight Band +)>) +TX, pantoea species+TX, pasteurella species +. >+TX, paecilomyces toenavatus (Pasteuria nishizawae) +TX, penicillium chrysogenum+TX, penicillium beijerinum (Penicillium billai) (. About.>+TX、/>) +TX, penicillium breve+TX, penicillium freudenreichii+TX, penicillium griseofulvum+TX, penicillium purpurogenum+TX, penicillium species+TX, pure green Kenymia+TX, phanerochaete (Phlebiopsis gigantean) per square>+ TX, phosphate-solubilizing bacteria->+TX, cryptophan+TX, phytophthora palmi +.>+TX, pichia anomala+TX, pichia guilliermondii (Pichia guilermondii) +TX, pichia membranefaciens+TX, pichia nail+TX, pichia stipitisRed yeast + TX, pseudomonas aeruginosa + TX, pseudomonas aureofaciens (Pseudomonas aureofasciens) (Spot-Less +.>) +TX, pseudomonas cepacia+TX, pseudomonas aeruginosa +.>+TX, pseudomonas rugosa (Pseudomonas corrugate) +TX, pseudomonas fluorescens strain A506 (Blight Band +)>) +TX, pseudomonas putida+TX, pseudomonas reactivatus (Pseudomonas reactans) +TX, pseudomonas species+TX, pseudomonas syringae +.>+TX, P.viridis+TX, P.fluorescens +.>+TX, pseudomonas floc (Pseudozyma flocculosa) strain PF-A22 UL (Sponodex +)>) +TX, puccinia longitus (Puccinia canaliculata) +TX, puccinia farrei (Puccinia thlaspeos) (Wood- >) +TX, pythium side (Pythium oligandrum) +TX and Pythium oligandrum%+TX、/>) +TX, pythium reesei +TX, rahnella aquatica (Rhanella aquatilis) +TX, rahnella species (Rhanella spp.) +TX, rhizobium (Rhizobia) (. Sub.f.)>+TX、) +TX, rhizoctonia (Rhizoctonia) +TX, rhodococcus globosus (Rhodococcus globerulus) AQ719+TX, rhodosporidium bicolor (Rhodosporidium diobovatum) +TX, rhodosporidium toruloides (Rhodosporidium toruloides) +TX, rhodotorula species (Rhodotorula spp.) +TX, rhodotorula glutinosa (Rhodotorula glutinis) +TX, rhodotorula graminea (Rhodotorula graminis) +TX, rhodotorula mucilaginosa (Rhodotorula mucilagnosa) +TX, rhodotorula rubra (Rhodotorula rubra) +TX, saccharomyces cerevisiae (Saccharomyces cerevisiae) +TX, rhodococcus rhodochrous (Salinococcus roseus) +TX, sclerotinia sclerotiorum (Sclerotinia minor) +TX, sclerotinia sclerotiorum @>+TX, acremonium species (Scytalidium spp.) +TX, scytalidium uredinicola +TX, spodoptera exigua nuclear polyhedrosis virus (Spodoptera exigua nuclear polyhedrosis virus) (. About.>+TX、/>) +TX, serratia marcescens (Serratia marcescens) +TX, serratia praecox (Serratia plymuthica) +TX, serratia species (Serratia spp.) +TX, chaetomium faecalis (Sordaria fimicola) +TX, spodoptera frugiperda nuclear polyhedrosis virus (Spodoptera littoralis nucleopolyhedrovirus) at right angles >+TX, rhodosporidium toruloides (Sporobolomyces roseus) +TX, stenotrophomonas maltophilia (Stenotrophomonas maltophilia) +TX, streptomyces hygroscopicus (Streptomyces ahygroscopicus) +TX, bai Qiulian mould (Streptomyces albaduncus) +TX, streptomyces defoliatus (Streptomyces exfoliates) +TX, streptomyces flavus (Streptomyces galbus) +TX, botrytis cinereaStreptomyces (Streptomyces griseoplanus) +TX and Streptomyces griseoviridis (Streptomyces griseoviridis)+TX, streptomyces lydicus (Streptomyces lydicus)/(S.lydicus)>+TX, streptomyces lydicus WYEC-108->+TX, streptomyces violaceus (Streptomyces violaceus) +TX, iron Ai Jiaomu (Tilletiopsis minor) +TX, iron Ai Jiaomu species (Tilletiopsis spp.) +TX, trichoderma asperellum (Trichoderma asperellum) (T34 depictinga combination of two or more species)>) +TX, trichoderma (Trichoderma gamsii)+TX, trichoderma atroviride (Trichoderma atroviride)/(S.atroviride)>+TX, trichoderma hook (Trichoderma hamatum) TH 382+TX, trichoderma harzianum bevel (Trichoderma harzianum rifai)+TX, trichoderma harzianum (Trichoderma harzianum) T-22 ()>+TX、PlantShield/>+TX、/>+TX、/>+TX, trichoderma harzianum T-39+TX, trichoderma atroviride (Trichoderma inhamatum) +TX, trichoderma koningii (Trichoderma koningii) +TX, trichoderma spp. Species (Trichoderma spp.) LC 52 +. >+TX, trichoderma lignin (Trichoderma lignorum) +TX, trichoderma longibrachiatum (Trichoderma longibrachiatum) +TX, trichoderma polyspora (Trichoderma polysporum) (Binab +)>) +TX, trichoderma (Trichoderma taxi) +TX, trichoderma viride (Trichoderma virens) +TX, trichoderma viride (originally called as gliocladium viride (Gliocladium virens) GL-21)+TX, trichoderma viride (Trichoderma viride) +TX, trichoderma viride strain ICC 080+TX, trichosporon species (Trichosporon spp.) +TX, trichosporon species (Trichotheca spp.) +TX, monascus roseus (Trichothecium roseum) +TX, typhula phacorrhiza strain 94670+TX, typhula phacorrhiza strain 94671+TX, alternaria nigra (Ulocladium atrum) +TX, alternaria schradfimbriae (Ulocladium oudemansii) and/or Alternaria farina>+TX, maize melanogaster (Ustilago maydis) +TX, various bacteria and micronutrient supplementation (Natural->) +TX, various fungi (Millennium +.>) +TX, verticillium chlamydosporium (Verticillium chlamydosporium) +TX, verticillium lecanii (Verticillium lecanii) (-)>+TX、/>)+TX、Vip3Aa20/>+TX, cladosporium decubitus (Virgibaclillus marismortui) +TX, xanthomonas campestris Poa pathogenic variant (Xanthomonas campestris pv Poae) +TX, B.buriei+TX, B.nematophilus;

plant extracts, including: pine tree oil+TX, azadirachtin (Plasma Neem)+TX、/>+TX、/>+TX、/>+TX), plant IGR (++TX)>+TX、/>) +TX, canola oil (Lilly Miller +.>) +TX, chenopodium ambrosioides (Chenopodium ambrosioides near ambrosioides)/(S)>+TX, chrysanthemum extract->+TX, neem oil extract +.>+TX, labiatae essential oil +.>+TX, clove-rosemary-peppermint and thyme oil extracts (Garden extract +.>) +TX, betaine->+TX, garlic+TX, lemon grass oil +.>+TX, neem oil+TX, catmint (Nepeta cataria) (catmint oil) +TX, nepeta catina+TX, nicotine+TX, oregano oil +.>+TX, pedaliaceae (Pedaliaceae) oil+TX, pyrethrum+TX, quillaja saponaria (Quillaja saponaria)/(A)>+TX, giant knotweed (Reynoutria sachalinensis) (-A.sub.L.)>+TX、/>) +TX, rotenone (Eco->) +TX, rutaceae (Rutaceae) plant extract ++>+TX, soybean oil (Ortho->) +TX, tea tree oil (Timorex->) +TX, thyme oil+TX, +.>MMF+TX、/>+TX, rosemary-sesame-peppermint-thyme and cinnamon extract mixture +.>+TX, clove-rosemary and peppermint extract mixtures (EF +.>) +TX, clove-peppermint-garlic oil and peppermint mixture (oil >) +TX, kaolinStorage dextran of +TX, brown algae->

Pheromones, including: black spot firefly pheromone (3M Sprayable Blackheaded Fireworm)) +TX, codling moth pheromone (Paramount dispenser- (CM)/Isomate)) +TX, grape leaf roller pheromone (3M MEC-GBM Sprayable +.>) +TX, leaf roller pheromone (3M MEC-LR Sprayable +.>) +TX, housefly pheromone (Musca) Snip7 Fly+TX、Starbar Premium Fly/>) +TX, pear borer pheromone (3M oriental fruit moth sprayable +)>) +TX, peach wing moth (Peachtree Borer) pheromone +.>+TX, tomato Pinworm (Tomato Pinworld) pheromone (3M Sprayable +.>) +TX, netostat powder (extract from palm tree) (Exosex +.>)+TX、(E+TX,Z+TX,Z)-3+TX,8+Tx,11 tetradecatrienacetate+Tx, (Z+Tx, E) -7+Tx,11+Tx, 13-hexadecatrienal+Tx, (E+Tx, Z) -7+Tx, 9-dodecadien-1-ylacetate+Tx, 2-methyl-1-butanol+Tx, calcium acetate+Tx, and the like>+TX、+TX、/>+tx, lavender senecide (Lavandulyl senecioate);

macrobiological agents (macrobials) including: short-range aphidius+TX, aphis aphis (Aphis ervi)+TX, acerophagus papaya +TX, ladybug distichondarium+TX, two star ladybug->+TX, two star ladybug->+TX, boschniakia rossica (Ageniaspis citricola) +TX, chaetoceros polyporus Boschniakia rossica+TX, amblyseius andersoni (Amblyseius andersoni) (-A. Fragrans) >+TX、/>) +TX, amblyseius californicus (Amblyseius californicus) (-A. Californicus)>+TX、/>) +TX, amblyseius cucumeris (>+TX、Bugline) +TX, amblyseius pseudoamblyseius->+TX, amblyseius spinosus (Bugline +)>+TX、) +TX, amblyseius oldhamii->+TX, bemisia tabaci fine bee (Amitus hesperidum) +TX, yuancherokee wing small bee (Anagrus atomus) +TX, dark abdomen long cable jumping small bee (Anagyrus fusciventris) +TX, kama long cable jumping small bee (Anagrus kamali) +TX, anagrus loecki+TX, pink long cable jumping small bee (Anagyrus pseudococci)>+TX, ericerus pela flat angle flea (Anicetus benefices) +TX, golden brood (Anisopteromalus calandrae) +TX, di Hua Zhu (Anthocoris nemoralis)+TX, short-range Aphis cerana (>+TX、/>) +TX, aphis bre (Aphelinus asychis) +TX, aphis gossypii parasitic wasp (Aphidius colemani)/(X)>+TX, aphidius gifuensis George +.>+TX, aphidius gifuensis George+TX, aphidius gifuensis George +.>+TX, aphid eating gall midge+TX, aphid eating goiter->+TX, linnan Huang Yaxiao bee+TX, inbus Huang Yaxiao bee+TX, ha's long tail rodent bee (Aprostocetus hagenowii) +TX, ant-shaped Cryptheca (Atheta coriaria)+TX, bumblebee species+TX, european bumblebee (Natupol->) +TX, european bumblebee (>+TX、/>) +TX, cephalonomia stephanoderis +TX, ladybug (Chilocorus nigritus) +TX, common green lacewing (Chrysoperla carnea)/(Peronotus obliquus) >+TX, common green lacewing+TX, red-blood sand fly (Chrysoperla rufilabris) +TX, cirrospilus ingenuus +TX, tetrakish-Ji wasp (Cirrospilus quadristria)tus) +TX, bai Xingju Royal bee (Citrostichus phyllocnistoides) +TX, closterocerus chamaeleon + TX, closterocerus genus species +TX, coccidoxenoides perminutus->+TX, porphyra tenera (Coccophagus cowperi) +TX, leidesia polycarpa (Coccophagus lycimnia) +TX, trichinella inferens (Huang Zupan) Trichinella inferens+TX, trichinella plutella+TX, cryptophanus mansoni (, meng's Cryptophanus japonicus)>+TX、/>) +TX, japanese square head A+TX, siberian off-jaw cocoon bee+TX, siberian off-jaw cocoon bee +.>+TX, pisum sativum (peas) potential She Yingji Apis cerana Fabricius->+TX, heilonggonella minutissima (Delphastus catalinae)/(N.sub.X)>+TX, delphastus pusillus +TX, diachasmimorpha krausii +TX, chrysomya longifolia+TX, diaparsis jucunda +TX, apis amabilis (Diaphorencyrtus aligarhensis) +TX, apis falcita She Yingji +TX, apis falcita She Yingji and Apis falcita+TX、/>) +TX, siberian off-jaw cocoon bee (>+TX、/>) +TX, tolyzus species+TX, lepium pythium and TX, and Aphis lividae (Encarsia->+TX、/>+TX、/>) +TX, aphis serovara (Eretmocerus eremicus)/(Temminck)>+TX, goldne aphidius (Encarsia guadeloupae) +TX, engizus sea (Encarsia haitiensis) +TX, and Aphis gracilis +TX, eretmoceris siphonini +TX, california myzus (Eretmocerus californicus) +TX, myzus persicae (Eretmocerus eremicus) (-A. Californica)>+TX、Eretline/>) +TX, aphis serovara (Eretmocerus eremicus)/(Temminck)>+TX, hai's oar horn aphidius+TX, mongolian oar horn aphidius (>+TX、/>) +TX, eretmocerus siphonini +TX, aleurites tetranychus (Exochomus quadripustulatus) +TX, mite goiter (Feltiella acarisuga)>+TX, mite goiter->+TX, apriona domestica+TX, fopius ceratitivorus +TX, formononetin (Wirless->) +TX, thin waist thrips ++>+TX, western spider mites (Galendromus occidentalis) +TX, lei's angular leg bees (Goniozus legeri) +TX, plutella xylostella+TX, harmoniella xylostella+Tx, harmoniella variegata+TX, heterodera species (Lawn +.>) +TX, heterodera mobilis (NemaShield +.>+TX、/>+TX、/>+TX、/>+TX、+TX、/>+TX、/>+TX、/>) +TX, heterodera grandis (Heterorhabditis megidis) (Nemasys +.>+TX、BioNem/>+TX、Exhibitline/>+TX、) +TX, ladybug (Hippodamia convergens) +TX, P.acutangula (Hypoaspis aculeifer) (-A.acutangula)>+TX、/>) +TX, dermatophagoides pteronyssinus (Hypoaspis mils) (Hypoline +.>+TX、/>) +TX, black tarsometatarsal (Lbalia leucospoides) +TX, lecanoideus floccissimus +TX, lemophagus errabundus +TX, trichromatic snap-on wasps (Leptomastidea abnormis) +TX, leptomastix dactylopii- >+TX, long angle Bolus (Leptomastix epona) +TX, lindorus lophanthae +TX, lipolexis oregmae +TX, and Leptophaea fork (Lucilia caesar)>+TX, aphidius pedunculata (Lysiphlebus testaceipes) +TX, aphidius gifuensis (Macrolophus caliginosus) (-A. Sub.f.)>+TX、Macroline/>+TX、/>) +TX, mesoseiulus longipes +TX, yellow broad-stalk jumping wasp (Metaphycus flavus) +TX, metaphycus lounsburyi +TX, keratosis greenfly (Micromus angulatus)/(1)>+TX, yellow flea bee (Microterys flavus) +TX, muscidifurax raptorellus and Spalangia cameroni+TX, neodryinus typhlocybae +TX, neoseiulus californicus (Neoseiulus californicus) +TX, amblyseius cucumeris (Neoseiulus cucumeris)>+TX, virtual new amblyseius (Neoseiulus fallacis) +TX, nesideocoris tenuis (++>+TX、/>) +TX, coppernix (Ophyra aeengens)/(Di)>+TX, dongyingzhu (Orius insolosus)+TX、Oriline/>) +TX, orius laevigatus (Orius laevigatus) (-jersey)>+TX、Oriline/>) +TX, orius majus (Oriline +.>) +TX, stink bug (Orius strigicollis)/(Testudinis)>+TX, pauesia juniperorum +TX, acid sauce ladybug, celastrus gracilis (Pediobius foveolatus) +TX, phasmarhabditis hermaphrodita +.>+TX, phymastichus coffea +TX, phytoseiulus macropilus +TX, phytoseiulus chile (Phytoseiulus persimilis) (-in depictinga group of animals) >+TX、Phytoline/>) +TX, siberian bugs (Podisus maculiventris)+TX, pseudacteon curvatus +TX, pseudacteon obtusus +TX, pseudacteon tricuspis +TX, pseudaphycus maculipennis +TX, pseudleptomastix mexicana +TX, mao Shimu lupulus (Psyllaephagus pilosus) +TX, homochromus short back cocoon (Psyttalia concolor) (complex) +TX, KRADIUM (Quadrastic spp.) +TX, rhyzobius lophanthae +TX, australian ladybug (Rodoli)a carpodialis) +TX, rumina decolate+TX, semielacher petiolatus +TX, and Myzus persicae (Sitobion avena)>+TX, heterodera plutella (Steinernema carpocapsae) (Nematac +.>+TX、/>+TX、BioNem/>+TX、/>+TX、/>+TX、/>) +TX, spodoptera exigua (+.>+TX、Nemasys/>+TX、BioNem/>+TX、/>+TX、/>+TX、/>+TX、Exhibitline/>+TX、/>+TX、/>) +TX, apis cerana (Steinernema kraussei) (Nemasys ]>+TX、BioNem/>+TX、Exhibitline/>) +TX, liibuf nematode (Steinernema riobrave)+TX、/>) +TX, gryllotalpa nematode (Steinernema scapterisci) (Nematac)) +tx, stannema (Steinernema spp.) + TX, steinernematid (Guardian)) +TX, ladybug (Stethorus punctillum) for deep spot mites>+TX, liangGauss wasp (Tamarixia radiate) +TX, tetrastichus setifer +TX, thripobius semiluteus +TX, chinese long tail wasp (Torympus sinesis) +TX, cabbage looper trichogramma (Trichogramma brassicae) (Tricho) line/>) +TX, cabbage looper trichogramma (Trichogramma brassicae)/(N.E.)>+TX, trichogramma (Trichogramma evanescens) +TX, trichogramma minor (Trichogramma minutum) +TX, trichogramma zebra (Trichogramma ostriniae) +TX, trichogramma widi (Trichogramma platneri) +TX, trichogramma minor (Trichogramma pretiosum) +TX, and scomitus variegata (Xanthopimpla stemmator); />

Other biological agents including: abscisic acid +TX,+TX, silver leaf bacteria (Chondrostereum purpureum) (Chontrol->) +TX, cephalosporium longum +.>+TX, copper octoate->+TX, delta trap (Trapline +.>) +TX, erwinia amylovora (Harpin) (-A. Amylovora)>+TX、Ni-HIBIT Gold/>) +TX, fatty acid derived from natural by-product of extra virgin olive oil +.>+TX, ferric phosphate->+TX, funnel trap (Trapline +.>)+TX、/>+TX、Grower's/>+TX, high brassinolide (Homo-brissolide) +TX, iron phosphate (Lilly Miller Worry Free Ferramol Slug)&Snail/>) +TX, MCP hail trap (Trapline->) +TX, parasitic insect Nannocheir sinensis (Microctonus hyperodae) +TX, mycoleptodiscus terrestris +.>+TX、/>+TX、/>+TX、/>+TX, pheromone Row net (thread->) +TX, potassium bicarbonate+TX, potassium salt of fatty acid +. >+TX, potassium silicate solution->+TX, potassium iodide+Potassium thiocyanate->+TX、/>+TX, spider venom+TX, microsporidian locusts (Semaspore Organic Grasshopper +.>) +TX, sticky trap (Trapline->+TX、Rebell/>) +TX and Capture (Takitrapline y +>)+TX；

(1) An antibacterial agent selected from the group consisting of:

(1.1) bacteria, examples of which are Bacillus mojavensis (Bacillus mojavensis) strain R3B (accession number NCAIM (P) B001389) (WO 2013/034938), from Mitsui Corp&Co.) of the subsidiary inc sirtuin united states corporation (Certis USA LLC) +tx; bacillus pumilus, particularly strain BUF-33, has the accession number NRRL 50185 (available asPart of the product was obtained from BASF, EPA accession number 71840-19) +tx; bacillus subtilis, in particular strain QST713/AQ713 (useful as Bayer process from the United statesSERENADE OPTI or SERENADE ASO available from the physical sciences company (Bayer CropScience LP), having NRRL accession No. B21661, U.S. patent No. 6,060,051) +tx; bacillus subtilis strain BU1814 (may be used as +.>PLUS、FLEX and->ExTRA obtained from Basoff company (BASF SE) +TX; bacillus subtilis variant amylolytic strain FZB24, having accession number DSM 10271 (available as +.>Or->ECO (EPA accession number 70127-5) is available from Novozymes (Novozymes) +tx; bacillus subtilis CX-9060, siemens USA+TX, a subsidiary of Sanchiku Co., ltd; bacillus species, in particular strain D747 (which can be DOUBLE +. >Obtained from combinatorial chemistry industries, inc (Kumiai Chemical Industry co., ltd.) having accession number FERM BP-8234, U.S. Pat. No. 7,094,592+tx; a paenibacillus species strain having accession number NRRL B-50972 or accession number NRRL B-67129, wo 2016/154297+tx; paenibacillus polymyxa, in particular strain AC-1 (e.g. from green biotechnology limited (Green Biotech Company ltd.))) +TX; pantoea agglomerans, in particular strain E325 (accession number NRRL B-21856) (as BLOOMTIME BIOLOGICAL) ^TM FD bipropesticide obtained from northwest agricultural products company (Northwest Agri Products) +tx; common rollerPseudomonas discos (Pseudomonas proradix) (e.g. from Sourcon Paden)>) +TX; and

(1.2) fungi, examples of which are Aureobasidium pullulans, in particular blastospores of the strain DSM14940, blastospores of the strain DSM14941 or mixtures of blastospores of the strains DSM14940 and DSM14941 (for example from the company Baio-Fei Murray, switzerland)And BLOSSOM->) +TX; aphanomyces aphis (Pseudozyma aphidis) (e.g. as disclosed in WO2011/151819 by the university of Hibernation, ixenms research development Co., ltd. (Yissum Research Development Company of the Hebrew University of Jerusalem)) +TX; saccharomyces cerevisiae (Saccharomyces cerevisiae), in particular strain CNCM No. 1-3936, CNCM No. 1-3937, CNCM No. 1-3938 or CNCM No. 1-3939 from Le Sifu company (Lesaffre et Compagnie) of France (WO 2010/086790);

(2) A biological fungicide selected from the group consisting of:

(2.1) bacteria, examples of which are Agrobacterium radiobacter strain K84 (e.g., from AgBiochem, eggy biochemistry, calif.)) +TX; agrobacterium radiobacter strain K1026 (e.g., NOGALL from Basv Corp.) ^TM ) +TX; bacillus subtilis variant amylolytic strain FZB24, having accession number DSM 10271 (available as +.>Or->ECO (EPA registration)No. 70127-5) obtained from novelimas (Novozymes) +tx; bacillus amyloliquefaciens, in particular strain D747 (which can be a Double Nickel ^TM Available from the chemical industry Co., ltd, having accession number FERM BP-8234, U.S. Pat. No. 7,094,592) +TX; bacillus amyloliquefaciens strain F727 (also known as strain MBI 110) (NRRL accession number B-50768, WO 2014/028521) (from Maroney biological Innovation Co., ltd. (Marrone Bio Innovations)) ->) +TX; bacillus amyloliquefaciens strain FZB42, accession number DSM 23117, (available as +.>Obtained from Ai Bitai Prop (ABiTEP) Germany) +TX; bacillus amyloliquefaciens isolate B246 (e.g., AVOGREN from university of Rajoba (University of Pretoria)) ^TM ) +TX; bacillus licheniformis, in particular strain SB3086, has accession number ATCC 55406, WO 2003/000051 (available as +. >Biological fungicides and GREEN RELEAF ^TM Obtained from novelin company,) +tx+tx; bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (from FMC Corp.)>(WG) and(WP)) +tx; bacillus methylotrophicus (Bacillus methylotrophicus) strain BAC-9912 (from the national academy of sciences of applied ecology) +TX; bacillus mojavensis (Bacillus mojavensis) strain R3B (accession number NCAIM (P) B001389) (WO 2013/034938), from Mitsui Corp. Siemens, inc. +TX; bacillus mycoides isolate having accession number B-30890 (available as BMJ +.>Or WG and LifeGard ^TM Obtained from Mitsui Corp, inc. + TX; bacillus pumilus, in particular strain QST2808 (which can be used as +.>Obtained from bayer crop science company of the united states, having accession number NRRL B-30087 and described in us patent No. 6,245,551) +tx; bacillus pumilus, in particular strain GB34 (which can be used as Yield +.>Obtained from Bayer AG, germany) +TX; bacillus pumilus, in particular strain BUF-33, has the accession number NRRL 50185 (available as part of the CARTISSA product from Basoff Inc. (BASF), EPA accession numbers 71840-19) +TX; bacillus subtilis, in particular strain QST713/AQ713 (available as SERENADE OPTI or SERENADE ASO from bayer crop science company (Bayer CropScience LP) in the united states, having NRRL accession No. B21661 and described in us patent No. 6,060,051) +tx; bacillus subtilis Y1336 (which can be used as WP is obtained from the baitai company (Bion-Tech) of taiwan of china and registered as a biological fungicide under accession numbers 4764, 5454, 5096 and 5277) +tx in taiwan of china; bacillus subtilis strain MBI 600 (available as SUBTILEX from Basoff, inc., having accession number NRRL B-50595, U.S. Pat. No. 5,061,495) +TX; bacillus subtilis strain GB03 (may be used as +.>Obtained from bayer company, germany) +tx; bacillus subtilis strain BU1814, (available as a strain)PLUS、/>FLEX and->ExTRA obtained from Basoff company) +TX; bacillus subtilis CX-9060, siemens USA+TX, a subsidiary of Sanchiku Co., ltd; bacillus subtilis KTSB strain (from Tang Naji company (DonagyS)) +.>) +TX; AVIV of Bacillus subtilis IAB/BS03 (from StK Bio-Ag Technologies) ^TM +.5 from Ai Dai Nature (Idai Nature)>) +TX; bacillus subtilis Strain Y1336 (useful asWP is obtained from the baitai company of taiwan of the chinese country and registered as a biological fungicide under accession numbers 4764, 5454, 5096 and 5277) +tx in taiwan of the chinese country; paenibacillus adnexus (Paenibacillus epiphyticus) (WO 2016/020371), from Basoff company +TX; paenibacillus polymyxa plant species (WO 2016/020371) from Basoff company +TX; a paenibacillus species strain having accession number NRRL B-50972 or accession number NRRL B-67129, wo 2016/154297+tx; pseudomonas aeruginosa strain AFS009, having accession number NRRL B-50897, WO 2017/019448 (e.g., HOWLER from agricultural biological community Innovative Co., USA (AgBiome Innovations)) ^TM And->) +TX; pseudomonas aeruginosa strains, in particular strain MA342 (e.g. from Paragri and Koppert)> And->+TX; pseudomonas fluorescens strain A506 (e.g., from New farm (NuFarm)) ->A506 +TX; pseudomonas putida (Pseudomonas proradix) (e.g., from Sorpa de Sorption)>) +TX; streptomyces griseus (Streptomyces griseoviridis) strain K61 (also known as Streptomyces flavus strain K61) (accession number DSM 7206) (from Waldra Corp (Verdera)) ->From Bayer Co (BioWorks)See crop protection 2006,25,468-475) +tx; streptomyces lydicus (Streptomyces lydicus) strain WYEC108 (also known as Streptomyces lydicus (Streptomyces lydicus) strain WYCD108 US) (from Norwesterner Co.)>And->) +TX; and

(2.2) fungi, examples of which are Leptosporum graminis, in particular strain AQ10 (e.g.AQ from Italian Corp. Of chemical Engineer (IntrachemBio Italia)) +TX; the strain of Leptosporum gracile AQ10, having accession number CNCM 1-807 (e.g., AQ +.A from Italian Corp., of Leptospira chemical Co., ltd.)>) +TX; aspergillus flavus strain NRRL 21882 (as +.A.F. from Santa Clara (Syngenta)/China chemical industry Co., ltd. (ChemChina)) >Whereas the known product) +tx; aureobasidium pullulans, in particular blastospore + TX of strain DSM 14940; aureobasidium pullulans, in particular blastospore + TX of strain DSM 14941; aureobasidium pullulans, in particular mixtures of blastospores of strains DSM14940 and DSM 14941 (e.g. +.f from Baio-Fei Murray, switzerland)>) +TX; chaetomium carotovorum (Chaetomium cupreum) (accession number CABI 353812) (e.g., BIOKUPRUM from agricultural life Co., ltd.) ^TM ) +TX; chaetomium globosum (Chaetomium globosum) (which may be +.>Obtained from lewil corporation (Rivale) +tx; cladosporium clavosum, strain H39, having accession number CBS122244, US2010/0291039 (foundation of research by Wach Ning Gen (Stichting Dienst Landbouwkundig Onderzoek)) +TX; phycomyces (Coniothyrium minitans), in particular strain CON/M/91-8 (accession number DSM9660, e.g. from Bayer crop science Biotechnology Co., ltd. (Bayer CropScience Biologics GmbH)) +TX; micrococcus micro Huang Yin (Cryptococcus flavescens), strain 3C (NRRL Y-50378), (B2.2.99) +tx; finger-shaped mould (Dactylaria candida) +TX; diroflumilast aloperin (Dilophosphora alopecuri) (available as TWIST +. >Obtain) +tx; fusarium oxysporum, strain Fo47 (as +.>Obtained from natural plant protection company (Natural Plant Protection) +tx; gliocladium (Gliocladium catenulatum) (synonym: endocarpium roseum (Clonostachys rosea f. Catenulate)) strain J1446 (e.g., prestop>) +TX; functions of gliocladium roseum (Gliocladium roseum) (also known as gliocladium roseum (Clonostachys rosea)), particularly strains 321U from Adjuvants Plus, such as Xue (Efficacy of Clonostachys rosea strain ACM941 and fungicide seed treatments for controlling the root tot complex of field pea [ gliocladium roseum strain ACM941 and Fungicide seed treatment to control pea root rot complex ]]Can Jour Plant Sci [ Canadian plant school newspaper ]]83 (3) 519-524) or strain IK726 (Jensen DF et al Development of a biocontrol agent for plant disease control with special emphasis on the near commercial fungal antagonist Clonostachys rosea strain 'IK726' [ particular emphasis was given to the development of biocontrol agents for plant disease control of the near-commercial fungal antagonist Scopulariella furcata strain 'IK726' ]Australas Plant Pathol [ Australian plant pathology ]]2007, 36:95-101) +tx; conidia of Verticillium lecanii (Lecanicillium lecanii) (originally designated Verticillium lecanii (Verticillium lecanii)) strain KV01 (e.g., from Kobert/Ailisda (Arysta))>) +TX; mei Ji Mei Yeast (Metschnikowia fructicola), especially strain NRRL Y-30752, (B2.2.3) +TX; aschersonia ochromosis (Microsphaeropsis ochracea) +tx; a malodorous rose fungus (Muscodor roseus), in particular strain A3-5 (accession No. NRRL 30548) +tx; penicillium bifidum (Penicillium steckii) (DSM 27859, WO 2015/067800) from Basoff+TX; penicillium vermiculosum (Penicillium vermiculatum) +TX; coriolus versicolor (Phlebiopsis gigantean) strain VRA 1992 (from Danst fermentation Co (Da)nstar organ)>C) +TX; pichia anomala, strain WRL-076 (NRRL Y-30842), U.S. Pat. Nos. 7,579,183+TX; candida floccosum (Pseudozyma flocculosa), strain PF-A22 UL (which can be used as +.>L is obtained from Plant Products co.) + TX, california; saccharomyces cerevisiae (Saccharomyces cerevisiae), in particular strain LASO2 (from agricultural yeasts and derivatives thereof company (Agro-Levures et Derilv), strain LAS117 cell wall (from Le Sifu company +. >A +.sub.f from Basiff company>) Strains CNCM No. 1-3936, CNCM No. 1-3937, CNCM No. 1-3938, CNCM No. 1-3939 (WO 2010/086790) +tx from company Le Sifu in france; new Prisis Li Mla Norsanifer (Simplicillium lanosoniveum) +TX; brucella flavum (Talaromyces flavus), strain v117b+TX; trichoderma reesei (Trichoderma asperelloides) JM41R (accession number NRRL B-50759) (TRITHO +.>) +TX; trichoderma asperellum (Trichoderma asperellum), particularly strain kd (e.g., T-Gro) +TX from the Amomuta biological control Co., ltd. (Andermatt Biocontrol); trichoderma asperellum (Trichoderma asperellum), particularly strain SKT-1, has accession number FERM P-16510 (e.g., from Mimo Corp., ltd.)>) Strain T34 (e.g., T34 from biological control technologies company of spain (Biocontrol Technologies s.l.), or strain from isegers (isagaro))ICC 012+TX; trichoderma atroviride (Trichoderma atroviride), in particular strain SC1 (having accession number CBS122089, WO 2009/116106 and U.S. Pat. No. 8,431,120 (from agricultural biologicals Co., ltd. (Bi-PA))), strain 77B (T77 from Andrite biocontrol Co., ltd.) or strain LU132 (e.g., sentinel) +TX from Aldrich technologies Co., ltd. (Agrimm Technologies Limited); trichoderma atroviride (Trichoderma atroviride), strain CNCM 1-1237 (e.g., agrauxin from Allakexin Inc. of France) WP) +tx; trichoderma atroviride (Trichoderma atroviride), strain number V08/002387+TX; trichoderma atroviride (Trichoderma atroviride), strain NMI V08/002388+TX; trichoderma atroviride strain NMI No. V08/002389+TX; trichoderma atroviride strain NMI No. V08/002390+TX; trichoderma atroviride (Trichoderma atroviride), strain LC52 (e.g., tenet) +TX from Argentina technologies Co., ltd; trichoderma atroviride (Trichoderma atroviride), strain ATCC 20476 (IMI 206040) +TX; trichoderma atroviride (Trichoderma atroviride), strain T11 (IMI 352941/CECT 20498) +TX; trichoderma atroviride (Trichoderma atroviride), strain SKT-1 (FERM P-16510), japanese patent publication (Kokai) No. 11-253151A+TX; trichoderma atroviride, strain SKT-2 (FERM P-16511), japanese patent publication (Xiaohai Co.) 11-253151A+TX; trichoderma atroviride, strain SKT-3 (FERM P-17021), japanese patent publication (Xiaohai Co.) 11-253151A+TX; trichoderma acremonium (Trichoderma fertile) (e.g., trichoplus product from Basoff) +TX; trichoderma (Trichoderma gamsii) (Trichoderma viride) strain ICC080 (IMI CC 392151CABI, e.g., bioDerma) +TX from Algories Somexico company (AGROBIOSOL DE MEXICO, S.A. DE C.V.); trichoderma (Trichoderma gamsii) (Trichoderma viride) strain ICC080 (IMI CC 392151 CABI) (which can be used as +. >Obtained from argan bejeer mexico company) +tx; trichoderma hook (Trichoderma harmatum) +tx; trichoderma hook (Trichoderma harmatum) with accession number ATCC 28012+tx; haTrichoderma reesei (Trichoderma harzianum) strain T-22 (e.g., trianum-P from Amomuta biological control Co., or Kobert Co., ltd.) or strain Cepa Simbt5 (from Xin Basi agricultural Co., sinxiose Agro)) +TX; trichoderma harzianum (Trichoderma harzianum) +TX; trichoderma harzianum (Trichoderma harzianum) ramp (rifai) T39 (e.g., makhreshim from Markett communications Arg Co., U.S.A.)) +TX; trichoderma harzianum (Trichoderma harzianum), strain ITEM 908 (e.g., trianium-P) +TX from Corbert; trichoderma harzianum (Trichoderma harzianum), strain TH35 (e.g., root-Pro from wheat Kang Teer company (Mycontrol) +TX; trichoderma harzianum (Trichoderma harzianum), strain DB 103 (available as +.>7456 available from da Gu Date biological laboratory (Dagutat Biolab) +tx; trichoderma polyspora (Trichoderma polysporum), strain IMI 206039 (e.g., binab TF WP) +TX from BINAB bioinnovation, inc. (BINAB Bio-Innovation AB) of Sweden; trichoderma subunit (Trichoderma stromaticum) having accession number Ts3550 (e.g., tricovab) +tx from the cacao plan execution committee (CEPLAC) of brazil; trichoderma viride (Trichoderma virens) (also known as Scopulariella viride (Gliocladium virens)), particularly strain GL-21 (e.g., soilGard) +TX from Sirtus, inc. of the United states; trichoderma viride (Trichoderma virens) strain G-41, originally designated as Scopulariella viride (Gliocladium virens) (accession number ATCC 2096) (e.g., from Bayer Co., USA >PLUS WP and->PLUS WP) +TX; trichoderma viride (Trichoderma viride), strain TV1 (e.g., trianum-P) +TX from Corbert; trichoderma viride, in particular strain B35 (Pietr et al 1993,Zesz.Nauk.A R w Szczecinie [ university of sundew agriculture science)Roll-up]161:125-137) +tx; trichoderma asperellum (Trichoderma asperellum) strain ICC012 (also known as Trichoderma harzianum (Trichoderma harzianum) ICC 012) (having accession number CABI CC IMI 392716) and Trichoderma giganteum (Trichoderma gamsii) (proto-Trichoderma viride) strain ICC 080 (having accession number IMI 392151) (e.g., BIO-TAM from Ixeg US corporation) ^TM And +.f. from Argentibayer Somexico Inc>) +TX; acidocella tenuifolia (Ulocladium oudemansii) strain U3, having accession number NM 99/06216 (e.g., from Botry-Zen Ltd. Of New Zealand)>And from Bayer Co Ltd) +TX; verticillium albolabrim (Verticillium albo-atrum) (Verticillium dahliae (V. Dahlia)) strain WCS850, having accession number WCS850, was deposited in the fungus culture center office (Central Bureau for Fungi Cultures) (e.g., DUTCH from Tree Care Innovation Co., ltd. (Tree Care Innovations))) +TX; verticillium chlamydosporium) +TX;

(3) A biocontrol agent having an effect of improving plant growth and/or plant health selected from the group consisting of:

(3.1) bacteria, examples of which are azospirillum bazedoxorum (Azospirillum brasilense) (e.g., from kuru (KALO, inc.)) +TX; azospirillum lipogenic (Azospirillum lipoferum) (e.g., VERTEX-IF from Terra Max, inc.) ^TM ) +TX; rhizobium azotemozolomide (Azorhizobium calulinodans), in particular strain ZB-SK-5+TX; azotobacter chroococcus (Azotobacter chrooc)occum), in particular strain h23+tx; azotobacter vinelandii (Azotobacter vinelandii), in particular strain ATCC 12837+tx; a mixture of azotobacter vinelandii (Azotobacter vinelandii) and Clostridium barbituric bacteria (Clostridium pasteurianum) (as +.>Obtained from alcun nass (Agrinos) +tx; bacillus amyloliquefaciens pm414 (from biofilm crop protection Co (Biofilm Crop Protection))) +TX; bacillus amyloliquefaciens SB3281 (ATCC # PTA-7542, WO 2017/205258) +TX; bacillus amyloliquefaciens TJ1000 (which can be used as +.>Obtained from novelin company) +tx; bacillus amyloliquefaciens, IN particular strain IN937a+TX; bacillus amyloliquefaciens, in particular strain FZB42 (e.g., from Ai Bitai Prop. Germany >) +TX; bacillus amyloliquefaciens BS27 (accession number NRRL B-5015) +TX; member EE128 of the family bacillus cereus (NRRL No. B-50917) +tx; member EE349 of the family Bacillus cereus (NRRL No. B-50928) +TX; bacillus cereus, in particular strain BP01 (ATCC 55675, e.g. from Ailisida Life sciences Co., USA (Arysta Lifescience))>) +TX; bacillus firmus, in particular strain CNMC 1-1582 (e.g.from Basoff's +.>) +TX; bacillus mycoides BT155 (NRRL No. B-50921) +TX; bacillus mycoides EE118 (NRRL No. B-50918) +TX; bacillus mycoides EE141 (NRRL No. B-50916) +TX; bacillus mycoides BT46-3 (NRRL No. B-50922) +TX; bacillus pumilus, especiallyStrain QST2808 (with accession number NRRL No. B-30087) +tx; bacillus pumilus, in particular strain GB34 (e.g. YIELD +.from Bayer crop science, germany>) +TX; siamese bacillus (Bacillus siamensis), in particular strain KCTC 13613T+TX; bacillus subtilis, in particular strain QST713/AQ713 (having NRRL accession number B-21661 and described in U.S. Pat. No. 6,060,051, may be used as +.>OPTI or->ASO obtained from bayer crop science company in the united states) +tx; bacillus subtilis, in particular strain AQ30002 (having accession number NRRL B-50421 and described in U.S. patent application No. 13/330,576) +tx; bacillus subtilis, in particular strain AQ30004 (and NRRL B-50455 and described in U.S. patent application No. 13/330,576) +tx; bacillus subtilis strain BU1814 (can be used as Obtained from basf corporation), bacillus subtilis rm303 (from biofilm crop protection corporation) +TX; bacillus thuringiensis BT013A (NRRL No. B-50924), also known as Bacillus thuringiensis 4Q7+TX; mixture of Bacillus licheniformis FMCH001 and Bacillus subtilis FMCH002 (as +.>(WG)、/>(WP) available from FMC company) +tx; bacillus subtilis, in particular strain MBI 600 (e.g. from Basv Corp +.>) +TX; bacillus tertequilensis (Bacillus tequilensis), in particular strain NII-0943+TX; soybean slow-growing rhizobia (Bradyrhizobium japonicum) (e.g., from Norwesterner's corporation +.>) +TX; thermomyces acidovorus (Delftia acidovorans), in particular strain RAY209 (e.g. from Braytox seed company (Brett Young Seeds)>) +TX; chickpea rhizobia (Mesorhizobium cicer) (e.g., nodulor) +tx from basf corporation; lactobacillus species (e.g. from Latopaph Corp (Lactupafi)) ->) +TX; rhizobium (Rhizobium leguminosarium biovar viciae) of the family leguminosae (e.g., nodulor) +tx from basf corporation; pseudomonas putida (Pseudomonas proradix) (e.g., from Sorpa de Sorption) >) +TX; pseudomonas aeruginosa, in particular strain PN1+TX; rhizobium leguminosae (Rhizobium leguminosarum), in particular rhizobium fabae (bv. Viceae) strain Z25 (accession number CECT 4585) +tx; paenibacillus polymyxa, in particular strain AC-1 (e.g. from green Biotechnology Co., ltd.>) +TX; serratia marcescens (Serratia marcescens), in particular strain SRM (accession number MTCC 8708) +TX; sinorhizobium meliloti (Sinorhizobium meliloti) strain NRG-185-1 (from Bayer crop science Co.)>GOLD) +tx; thiobacillus sp (e.g. from claude Ltd (croplaid Ltd) in the uk)) +TX; and

(3.2) fungi, examples of which are Cytophytia lilacina (Purpureocillium lilacinum) (once known as Paecilomyces lilacinus (Paecilomyces lilacinus)) strain 251 (AGAL 89/030550, e.g., bioAct) +TX from Bayer crop science biological company; penicillium bailii (Penicillium bilaii), strain ATCC 22348 (e.g., from Aceleron BioAg, inc.)) Yellow basket (Talaromyces flavu), strain v117b+tx; trichoderma atroviride strain CNCM 1-1237 (e.g., from Alocoxine, france) WP), trichoderma viride, e.g., strain B35 (Pietr et al, 1993,Zesz.Nauk.A R w Szczecinie [ university of sundown agriculture science volume)]161:125-137) +tx; trichoderma atroviride (Trichoderma atroviride) strain LC52 (also known as Trichoderma atroviride (Trichoderma atroviride) strain LU132, e.g. Sentinel) +TX from Argentina technologies Co., ltd; trichoderma atroviride (Trichoderma atroviride) strain SC1 (described in International application No. PCT/IT 2008/000196) +TX; trichoderma asperellum (Trichoderma asperellum) strain kd (e.g., T-Gro) +TX from the Amyda biological control company; trichoderma asperellum (Trichoderma asperellum) strain Eco-T (plant health products Co., new Zealand), trichoderma harzianum (Trichoderma harzianum) strain T-22 (e.g., trianum-P) +TX from the Amyda biological control Co., or the Kobert Co.; myrothecium verrucosa strain AARC-0255 (e.g., diTera from Ci Hua Lun bioscience (Valent Biosciences) ^TM ) +TX; penicillium beijerinum (Penicillium bilaii) strain ATCC20851+TX; pythium gracile (Pythium oligandrum) strain M1 (ATCC 38472, e.g., polyversum) +T from Jettack's By-Omega Propiddy (Bioprepry)X is a group; trichoderma viride (Trichoderma virens) strain GL-21 (e.g., from Siderurgica, USA +. >) +TX; the strain verticillium alboldii (Verticillium albo-atrum) (verticillium dahliae) WCS850 (CBS 276.92, e.g., dutch Trig) +tx from tree care innovation company; trichoderma atroviride (Trichoderma atroviride), in particular strain No. V08/002387, strain No. NMI No. V08/002388, strain No. NMI No. V08/002389, strain No. NMI No. V08/002390+TX; trichoderma harzianum (Trichoderma harzianum) strain ITEM 908, trichoderma harzianum (Trichoderma harzianum) strain TSTh20+TX; trichoderma harzianum (Trichoderma harzianum) strain 1295-22+TX; a strain of Pythium gracile (Pythium oligandrum) Dv74+TX; a Mi Ershi Armillariella (Rhizopogon amylopogon) (e.g., contained in Myco-Sol from Frena chemical company (Helena Chemical Company) +TX; fulvis (Rhizopogon fulvigleba) (e.g., contained in Myco-Sol from Frena chemical Co.)) +TX; trichoderma viride (Trichoderma virens) strain GI-3+TX;

(4) An insecticidal active biocontrol agent selected from the group consisting of

(4.1) a bacterium, an example of which is Agrobacterium radiobacter strain K84 (Galltrol) +TX from Eggy biochemistry Co; bacillus amyloliquefaciens, in particular strain PTS-4838 (e.g., AVEO) +TX from the Coulter of Coulomb bioscience in the United states; bacillus firmus, in particular strain CNMC 1-1582 (e.g. from Basoff Corp ) +TX; bacillus mycoides isolate j (e.g., bmJ) +tx from the company songarland usa, san francisco; bacillus sphaericus (Bacillus sphaericus), in particular serotype H5a5b strain 2362 (strain ABTS-1743) (e.g. from the company Ci.Hua.Lun bioscience in the United states>) +TX; bacillus thuringiensis catfish subsp.aizawai), in particular strain ABTS-1857 (SD-1372, for example +.f from the company coulomb bioscience>) +TX; bacillus thuringiensis catzemia (subsp. Aizawai), in particular serotype H-7 (e.g. from the company Ci.Hua.Lun bioscience in the United states)>WG) +tx; bacillus thuringiensis israel (Bacillus thuringiensis israelensis) strain BMP 144 (e.g., from Beckel microorganism products Inc. (Becker Microbial Products) of Illinois)>) +TX; bacillus thuringiensis subspecies israeli (serotype H-14) strain AM65-52 (accession number ATCC 1276) (e.g., from the company Cistanchis of Coulomb bioscience in the United states)>) +TX; bacillus thuringiensis catze (subsp. Aizawai) strain GC-91+TX; bacillus thuringiensis Colmeri variant (var. Colmeri) (e.g., TIANBAOBTC) +TX from Hezhou, river and sea chemical company (Changzhou Jianghai Chemical Factory); bacillus thuringiensis strain Buibui+TX; bacillus thuringiensis Coulosa subspecies (subsp. Kurstaki) strain BMP 123, from Becker microbial products, inc. + TX, illinois; bacillus thuringiensis subspecies kurstaki (Bacillus thuringiensis subsp. Kurstaki) strain BMP 123 (from Bakel microbial products, illinois), e.g., BARITONE+TX from Bayer crop science, inc.; bacillus thuringiensis subspecies coulostaki (subsp. Kurstaki) strain HD-1 (e.g., from the company of the biological sciences of the Chinese forest. America- >ES) +tx; bacillus thuringiensis Coulosa variant strain EVB-113-19 (example)For example, from AEF Global>) +TX; bacillus thuringiensis subspecies (subsp. Kurstaki) strain ABTS 351+TX; bacillus thuringiensis subspecies (subsp. Kurstaki) strain PB 54+TX; bacillus thuringiensis subspecies (subsp. Kurstaki) strain SA 11, (JAVELIN) +TX from Siderurgica, U.S.A.; bacillus thuringiensis subspecies (subsp. Kurstaki) strain SA 12 (THURICID) +TX from Sisorus wire Co., U.S.A.; bacillus thuringiensis subspecies (subsp. Kurstaki) strain EG 2348 (LEPINOX) +TX from Siderurgica, USA; bacillus thuringiensis subspecies (subsp. Kurstaki) strain EG 7841 (CRYMAX) +TX from Siderurgica, U.S.A.; bacillus thuringiensis (subsp. Tenebrionis) strain NB 176 (SD-5428, e.g., from Bayesian company (BioFa) of Germany)FC) +tx; bacillus laterosporus (Brevibacillus laterosporus) (laterl) +tx from the company liberalium (Ecolibrium Biologicals); burkholderia species, in particular, the strain A396 of Burkholderia (Burkholderia rinojensis) of Rankine (also known as the strain MBI 305 of Burkholderia (Burkholderia rinojensis)) having accession numbers NRRL B-50319+TX, WO 2011/106491 and WO 2013/032693+TX, for example, MBI206 TGAI and MBI206 TGAI from the company of biological innovation of Maroney >) +TX; purple bacillus (Chromobacterium subtsugae) from iron-cedar, in particular the strain PRAA4-1T (MBI-203+TX; e.g. from the company Maroney bioInnova>) +TX; scabies fly (Lecanicillium muscarium) Ve6 (MYCOTAL) +TX from Kobert Co; bacillus thuringiensis (Paenibaci)Bacillus popilliae) (Bacillus thuringiensis (Bacillus popilliae) +TX; for example MILKY SPORE POWDER from St. Gabriel Laboratories ^TM And MILKY SPORE GRANULAR ^TM ) +TX; papanicolaou sp strain Pn1 (CLARIVA) +TX from Nemada/China chemical company; serratia marcescens (Serratia entomophila) (e.g., latifen seed Co., wright tson Seeds)>) +TX; serratia marcescens (Serratia marcescens), in particular strain SRM (accession number MTCC 8708) +TX; trichoderma asperellum (Trichoderma asperellum) (Trichoderma asperellum) +TX from Noveyi; bi Tisi Wo Baqi subunit (Wolbachia pipientis) ZAP Strain (e.g., ZAP from Moscottpost Co., ltd. (Mosquito mate))) +TX; and

(4.2) fungi, examples of which are beauveria bassiana (Beauveria bassiana) strain ATCC 74040 (e.g., from Italian Corp. Of chemical organism of Earthwest) ) +TX; beauveria bassiana (Beauveria bassiana) strain GHA (accession number ATCC74250, e.g., +.f from Lafleme International company (Laverlam International Corporation))>ES and->) +TX; beauveria bassiana (Beauveria bassiana) strain ATP02 (accession No. DSM 24665) +tx; isaria fumosorosea (Isaria fumosorosea) (previously known as Paecilomyces fumosoroseus (Paecilomyces fumosoroseus) strain Apopka 97) (PREFERAL) +TX from Sepro; metarrhizium anisopliae 3213-1 (deposited under NRRL accession number 67074) (WO 2017/066094+TX; pioneer International company (Pioneer Hi-Bred Internationa)) +TX; roots's diseaseMetarrhizium anisopliae (Metarhizium robertsii) 15013-1 (deposited under NRRL accession number 67073) +TX; metarhizium anisopliae 23013-3 (deposited under NRRL accession number 67075) +TX; paecilomyces lilacinus strain 251 (MELOCON) +TX from Sirtus corporation of America; rankine pestivirus (Zoophtora radicans) +TX;

(5) A virus selected from the group consisting of: particle virus (GV) +tx of brown moth (apple moth (summer fruit tortrix)); cydia pomonella/codling moth) Granulosis Virus (GV) +tx; cotton bollworm (Helicoverpa armigera/cotton bollworm) Nuclear Polyhedrosis Virus (NPV) +tx; beet armyworm (Spodoptera exigua/beet armyworm) mnpv+tx; spodoptera frugiperda (fall armyworm) mnpv+tx; spodoptera littoralis (african cotton leaf moth) npv+tx;

(6) Bacteria and fungi selected from the following that can be added as "inoculants" to plants or plant parts or plant organs and promote plant growth and plant health due to their specific characteristics: agrobacterium species (Agrobacterium spp.) +tx; rhizobium azotemozolomide (Azorhizobium caulinodans) +TX; azospirillum species + TX; azotobacter species + TX; slow-growing rhizobium species + TX; burkholderia species (Burkholderia spp.), in particular Burkholderia cepacia (Burkholderia cepacia) (originally referred to as Pseudomonas cepacia) +TX; megasporangium species or megasporangium monospora (Gigaspora monosporum) +tx; saccharum species (Glomus spp.) + TX; lepidocrocea species (Laccaria spp.) +tx; lactobacillus buchneri (LactoBacillus buchneri) +tx; saccharum-like species (agallomus spp.) + TX; calvatia (Pisolithus tinctorus) +TX; pseudomonas species+TX; rhizobium species, in particular rhizobium trilobatum (Rhizobium trifolii) +tx; a rhizopus species (rhizopopgon spp.) + TX; scleroderma spp + TX; the species of the genus nigella (suilu spp.) + TX; streptomyces species+TX;

(7) Plant extracts and products (including proteins and secondary metabolites) formed by microorganisms useful as biocontrol agents selected from the group consisting of garlic (Allium sativum) (NEMGUARD+TX from Ai Kesi Prime (Eco-Spray)); armour-Zen+tx; artemisia absinthium (Artemisia absinthium) +TX; azadirachtin (e.g., AZATIN XL) +TX from Sirttail, U.S.A.; biokeeper WP+TX; crucifer (brassica ceae) extracts, in particular canola meal or mustard meal+tx; semen cassiae (Cassia nigra) +tx; celastrus angulatus (Celastrus angulatus) +TX; chenopodium ambrosioides (Chenopodium anthelminticum) +tx; chitin (Chitin) +tx; dryopteris filix-mas) +TX; horsetail (Equisetum arvense) +tx; fortune Aza+TX; fungaston+TX; heads Up (quinoa saponin (Chenopodium quinoa saponin) extract) +TX; PROBLAD (naturally occurring Blad polypeptide from lupin seed), siderurgica+TX; FRACTURE (naturally occurring Blad polypeptide from lupin seed), FMC Inc. + TX; pyrethrum (Pyrethrum)/pyrethrin (Pyrethrins) +tx; sophora flavescens (Quassia amara) +TX; oak (query) +tx; quillaja (Quillaja) extract (QL AGRI 35 from Basv) +TX; giant knotweed extract (REGALLIA/REGALIA MAXX from Marrone Bio); "Requiem ^TM Insecticide "+tx; rotenone+tx; ryanodine (ryanodine)/ranitidine (ryanodine) +tx; comfrey (Symphytum officinale) +tx; chrysanthemum+tx; thymol (Thymol) +tx; thymol (Thymol) mixed with Geraniol (Geraniol) (CEDROZ) +tx from Eden Research, eden Research; thymol (Thymol) mixed with Geraniol (Geraniol) and Eugenol (Eugenol) (MEVALONE) +tx from meadow research company; triact70+TX; triCon+TX; saussurea involucrata (tropaeolum majus) +tx; melaleuca alternifolia extract (Melaleuca alternifolia) (timex GOLD) +tx from stoketon company (STK); nettle (Urtica dioica) +TX; veratrine (Veratrin) +tx; and white mistletoe (Viscum album) +tx; and

safeners such as clomazone+tx, cloquintocet-mexyl (including cloquintocet-mexyl) +tx, cyclopropanesulfonamide+tx, dichloropropylamine+tx, clomazone (including clomazone-ethyl) +tx, clomazone+tx, fluroxypyr+tx, clomazone+tx, bisbenzoxazole acid (including bisbenzoxazole acid-ethyl) +tx, mefenpyr (mefenpyr) (including mefenpyr-diethyl) +tx, clomazone (metamix) +tx, and mefenamic acid+tx.

Brackets after the active ingredientReference in (a) such as [3878-19-1 ]Refers to chemical abstract accession numbers. The above described mixed formulations are known. The active ingredients are contained in' The Pesticide Manual [ handbook of pesticides ]]"[ The Pesticide Manual-AWorld Compendium [ handbook of pesticides-Global overview ]]The method comprises the steps of carrying out a first treatment on the surface of the 13 th edition; editing: c.d.s.tomlin; the British Crop Protection Council [ British crop protection Committee ]]]In which they are described with the entry numbers given in parentheses above for the particular compound; for example, the compound "avermectin" is described by entry number (1). In "[ CCN]"in the case of the above addition to a specific compound, the compound in question is included in the outline of the generic name of" Compendium of Pesticide Common Names [ pesticide ]]"in, it can be on the internet [ a.wood;Compendium of Pesticide Common Names，Copyright1995-2004]obtaining; for example, the compound "acetylfipronil" is described in Internet addresseshttp:// www.alanwood.net/pesticides/acetoprole.htmlIs a kind of medium.

Most of the active ingredients described above are indicated by the so-called "common name" hereinabove, the corresponding "ISO common name" or another "common name" being used in different situations. If the name is not "common name", the name species used is replaced with the name given in parentheses for the particular compound; in this case, IUPAC name, IUPAC/chemical abstract name, "chemical name", "traditional name", "compound name" or "study code" are used, or "alias" is used if neither one of those names nor "universal name" is used. "CAS registry number" means a chemical abstract registry number.

The active ingredient mixtures of compounds of the formula I selected from the compounds defined in table P with the above-mentioned active ingredients comprise a compound selected from the compounds defined in table P and the active ingredients described above, these compounds preferably being in a mixing ratio from 100:1 to 1:6000, in particular from 50:1 to 1:50, more in particular in a ratio from 20:1 to 1:20, even more in particular from 10:1 to 1:10, very in particular from 5:1 to 1:5, particularly preferably in a ratio from 2:1 to 1:2, and also preferred are ratios from 4:1 to 2:1, especially ratios of 1:1, or 5:1, or 5:2, or 5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or 1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or 2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or 4:35, or 1:75, or 2:75, or 1:6000, or 1:3000, or 1:1500, or 1:350, or 2:350, or 1:750, or 2:750, or 4:750. Those mixing ratios are by weight.

The compounds and mixtures as described above may be used in a method of controlling pests, which method comprises applying a composition comprising a compound or mixture as described above, respectively, to the pest or its environment, a method for treating the human or animal body by surgery or therapy, and a diagnostic method carried out on the human or animal body.

The mixture of a compound of formula I comprising a compound selected from the group defined in table X, table Xa and table P and one or more active ingredients as described above may be applied, for example, as follows: these single active ingredients are used in combination in a single "water-in-use" form, in a combined spray mixture (which consists of separate formulations of the single active ingredient components, such as a "tank mix"), and when applied in a sequential manner (i.e., one after another for a moderately short period of time, such as hours or days). The order of administration of the compounds of formula I and the active ingredients as described above is not critical to the practice of the invention.

The compositions according to the invention may also comprise other solid or liquid adjuvants, such as stabilizers, for example non-epoxidized or epoxidized vegetable oils (for example epoxidized coconut oil, rapeseed oil or soybean oil), defoamers (for example silicone oil), preservatives, viscosity regulators, binders and/or tackifiers, fertilizers or other active ingredients for achieving specific effects, for example bactericides, fungicides, nematicides, plant activators, molluscicides or herbicides.

The compositions according to the invention are prepared in a manner known per se, in the absence of auxiliaries, for example by grinding, sieving and/or compressing the solid active ingredients; and in the presence of at least one auxiliary, for example by intimately mixing the active ingredient with one or more auxiliary and/or grinding the active ingredient with one or more auxiliary. The processes for preparing the compositions and the use of compounds of the formula I for preparing these compositions are also subjects of the invention.

Methods of application of these compositions, i.e. methods of controlling pests of the above-mentioned type, such as spraying, atomizing, dusting, brushing, coating, broadcasting or pouring-which are selected to be suitable for the intended purpose of the prevailing circumstances-and the use of these compositions for controlling pests of the above-mentioned type are further subjects of the invention. Typical concentration ratios are between 0.1ppm and 1000ppm, preferably between 0.1ppm and 500ppm, of active ingredient. The application rate per hectare is generally from 1g to 2000g of active ingredient per hectare, in particular from 10g/ha to 1000g/ha, preferably from 10g/ha to 600g/ha, in particular from 10g/ha to 200g/ha.

In the field of crop protection, the preferred application method is to apply to the foliage of these plants (foliar application), it being possible to select the frequency and rate of application to correspond to the risk of infestation by the pest in question. Alternatively, the active ingredient may reach the plants via the root system (systemic action) by impregnating the locus of these plants with a liquid composition or by introducing the active ingredient in solid form into the locus of the plants (for example into the soil, for example in the form of granules (soil application)). In the case of rice crops, such granules may be metered into flooded rice fields.

The compounds of formula I and their compositions according to the invention are also suitable for the protection of plant propagation material (for example seeds such as fruits, tubers or grains, or nursery plants) against the types of pests mentioned above. The propagation material may be treated with the compound prior to planting, e.g. seeds may be treated prior to sowing. Alternatively, the compound may be applied to the seed kernel (coating) by dipping the kernel into a liquid composition or by applying a layer of a solid composition. It is also possible to apply these compositions while the propagation material is planted at the application site, for example during drill seeding, the compositions are applied to seed furrows. These methods of treatment for plant propagation material and plant propagation material so treated are further subjects of the invention. Typical treatment rates will depend on the plant to be controlled and the pests/fungi and will generally be between 1 gram and 200 grams per 100kg seed, preferably between 5 grams and 150 grams per 100kg seed, such as between 10 grams and 100 grams per 100kg seed.

The term seed includes all kinds of seeds as well as plant propagules including but not limited to true seeds, seed pieces, sucking discs, grains, lepidocrocas, fruits, tubers, grains, rhizomes, cuttings, cut shoots and the like and in preferred embodiments means true seeds.

The invention also includes seeds coated or treated with or containing a compound having formula I. Although more or less of the ingredients may penetrate into the seed material depending on the method of application, the term "coated or treated with … … and/or containing" generally means that the active ingredient is on the surface of the seed at the time of application, in most cases. When the seed product is (re) planted, it may absorb the active ingredient. In an embodiment, the present invention makes it possible to obtain plant propagation material having attached thereto a compound having formula I. Furthermore, a composition comprising plant propagation material treated with a compound of formula I is thereby made available.

Seed treatment includes all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking, and seed pelleting. The seed treatment application of the compounds of formula I may be carried out by any known method, such as spraying or dusting the seeds prior to or during sowing of the seeds.

The compounds of the invention can be distinguished from other analogues by greater efficacy and/or different pest control at low application rates Compounds, which can be used by the person skilled in the art using experimental procedures, with lower concentrations (if required), for example 10ppm, 5ppm, 2ppm, 1ppm or 0.2ppm; or lower application rates, e.g. per m ² 300. 200 or 100mg AI. Greater efficacy can be observed by increased safety (against above-ground and below-ground non-target organisms (such as fish, birds and bees), improved physico-chemical properties or increased biodegradability).

In each aspect and embodiment of the present invention, "consisting essentially of … …" and variants thereof are preferred embodiments of "comprising" and variants thereof, and "consisting of … …" and variants thereof are preferred embodiments of "consisting essentially of … …" and variants thereof.

The disclosure of the present application makes available each combination of embodiments disclosed herein.

It should be noted that the disclosure herein regarding compounds having formula I applies equally to compounds having formula Ia, ib, ic, id, ie, if, ig and each of table X, table Xa and table P.

The compounds of the invention can be distinguished from other similar compounds by greater efficacy and/or different pest control at low application rates, which can be used by the skilled artisan using experimental procedures with lower concentrations (if desired), for example 10ppm, 5ppm, 2ppm, 1ppm or 0.2ppm; or lower application rates, e.g. per m ² 300. 200 or 100mg AI. Greater efficacy can be observed by increased safety (against above-ground and below-ground non-target organisms (such as fish, birds and bees), improved physico-chemical properties or increased biodegradability).

Biological examples:

the following examples serve to illustrate the invention. Certain compounds of the present invention may be distinguished from known compounds by greater efficacy at low application rates, as may be demonstrated by one skilled in the art using the experimental procedure outlined in the examples, using lower application rates (if desired), such as 50ppm, 24ppm, 12.5ppm, 6ppm, 3ppm, 1.5ppm, 0.8ppm, or 0.2 ppm.

Resistant plutella xylostella R1Larval killing agent L3 (plutella xylostella (Diamond back moth)), feeding/contacting

The chinese cabbage plants are sprayed with the diluted test solution in the application chamber. The excised leaves were placed in petri dishes with moistened filter paper and infested 1 day after application of 10L3 of the polyclonal plutella xylostella larvae with the G4946E resistance mutation. Samples were evaluated for mortality and growth regulation 4 days after infestation.

CTPR was used as a standard and the resistance factor obtained for this line was 146.

The source is as follows:

in 2012, plutella xylostella resistant line R1 was originally collected from taiwan, which carries the RyR mutation G4946E conferring diamide resistance. The line was raised on cabbage plants (cabbage (Brassica Aleracea)) and selected approximately every two weeks with chlorantraniliprole.

The following compounds according to the invention give at least 80% control of the plutella xylostella resistant line R1 at 50ppm or less:

P2、P3、P4、P6、P7、P12、P13、P16、P19、P21、P22、P23、P24。

resistant plutella xylostellaR4 (plutella xylostella) larvicide L1, feeding/contacting

24-well microtiter plates with artificial feed were treated by pipetting with aqueous test solutions prepared from 10,000 ppm DMSO stock solutions. After drying, about 30 plutella eggs were pipetted through the plastic template onto the gel blotting paper and the plates were blocked with it. Samples were evaluated for mortality compared to untreated samples 8 days after infestation.

CTPR was used as a standard and a resistance factor of 242 was obtained for this strain

The source is as follows:

in 2021, the plutella xylostella resistant line R4 was derived from laboratory, and was obtained by crossing the R1 line with a sensitive plutella xylostella line (SUS) raised in laboratory. R4 can be fed and tested with artificial feed and also carries the RyR mutation G4946E that confers diamide resistance. The strain was selected with chlorantraniliprole approximately every two weeks.

The following compounds according to the invention gave at least 80% control of the plutella xylostella resistant line R4 at 50ppm or less:

P1、P2、P4、P16、P21、P23、P24

description of in vitro assay methods

Human embryonic kidney cells expressing the plutella xylostella (Plutella xylostella) (plutella xylostella (Diamond back moth)) and containing the G4946E resistance mutation are loaded with a Fluo-8No Wash (NW) calcium sensitive dye that responds to changes in intracellular calcium by fluorescence (e.g., stimulated by activation of the lanine receptor). Test compounds were added at a 10-fold ratio to 384-well plates containing dye-loaded cells, and fluorescence signals were measured using Hamamatsu FDSS (functional drug screening system). Dose-response curves were plotted to estimate EC ₅₀ 。EC ₅₀ Reference standards (cyantraniliprole) were normalized to the assay to account for inter-assay variability. The ratio of the given compounds is then obtained by the formula:

R _EC50 ＝EC ₅₀ (Compound)/EC ₅₀ (cyantraniliprole). R is R _EC50 The activity of the compound with the ratio less than or equal to 1 is equal to or higher than that of cyantraniliprole.

According to the invention, R is obtained from the following compounds _EC50 The ratio is less than or equal to 1: p.

The following table provides R for the compounds _EC50

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Claims (15)

1. A method for combating and controlling diamide resistant insects to effect the following:

(i) Reducing damage to plants, the method comprising applying to the insects, to a locus of the insects, or to plants susceptible to attack by the insects an effective amount of a compound of formula I and or an agronomically acceptable salt, isomer, enantiomer, tautomer and/or N-oxide of the compound of formula I; or (b)

(ii) Protecting plant propagation material, the method comprising treating the propagation material or the locus where the propagation material is grown with an effective amount of a compound of formula I and/or an agronomically acceptable salt, isomer, enantiomer, tautomer and/or N-oxide of the compound of formula I;

wherein the compound of formula I is

Wherein the method comprises the steps of

A is O or S;

R ₁ is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Haloalkyl, or C ₃ -C ₆ Cycloalkyl;

G ₁ 、G ₂ and G ₃ And G ₁ And G ₃ The two carbon atoms attached together form a heteroaromatic or partially saturated ring system, wherein G ₁ 、G ₂ And G ₃ Selected from nitrogen, sulfur, oxygen and carbon, the bond between two consecutive G's being a single bond, a double bond or an aromatic bond, wherein at least one G represents nitrogen, sulfur or oxygen, and no more than two G's may be oxygen or sulfur, and where two G's are oxygen and/or sulfur they are separated by one carbon atom;

from G ₁ 、G ₂ 、G ₃ And the five-membered ring formed by the two carbon atoms to which they are attached is substituted with one to three groups independently selected from X1-Z, with the proviso that

X1 is a direct bond, Z is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, (C) ₁ -C ₆ Alkyl) C (=O), (C ₃ -C ₆ Cycloalkyl) C (=o), (C ₁ -C ₆ Alkoxy) C (=o), (C ₃ -C ₆ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkyl sulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, or C ₁ -C ₄ A haloalkylsulfonyl group; or X1 is C ₁ -C ₆ Alkyldiyl, Z is halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, (C) ₁ -C ₆ Alkyl) C (=O), (C ₃ -C ₆ Cycloalkyl) C (=o), (C ₁ -C ₆ Alkoxy) C (=o), (C ₃ -C ₆ Cycloalkoxy) C (=o), benzyl, halobenzyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkyl sulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, C ₁ -C ₄ Haloalkyl sulfonyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, cyano, C ₁ -C ₃ Alkylcarbonyloxy, or C ₃ -C ₆ Cycloalkyl carbonyloxy;

R ₃ is phenyl, or a 6 membered heteroaromatic ring, each of which is unsubstituted or is one to three independently selected from R ₆ Is substituted by a substituent of (a);

R ₄ is hydrogen, halogen, C ₁ -C ₆ Alkyl, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, C ₃ -C ₆ Cyanocycloalkyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, or X2-Y, wherein X2 is C ₁ -C ₆ Alkyldiyl or C ₁ -C ₆ Haloalkyl-di-and

Y is cyano, C ₂ -C ₆ Alkenyl, C ₂ -C ₆ Alkynyl, C ₁ -C ₆ Alkoxy, C ₁ -C ₆ Haloalkoxy, C ₃ -C ₆ Cycloalkyl, C ₃ -C ₆ Halogenated cycloalkyl, C ₁ -C ₄ Alkyl sulfanyl, C ₁ -C ₄ Alkylsulfinyl, C ₁ -C ₄ Alkylsulfonyl, C ₁ -C ₄ Haloalkylsulfanyl, C ₁ -C ₄ Haloalkyl sulfinyl, C ₁ -C ₄ Haloalkylsulfonyl, benzyloxy, halobenzyloxy, 5-or 6-membered heteroaromatic ring which is unsubstituted or is selected from one to three independently R ₇ Substituted, or 9-or 10-membered heteroaromatic bicyclic systems, unsubstituted or substituted by one to three independently selected R ₇ Substitution;

R ₆ independently selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₁ -C ₃ Haloalkylthio, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, (C) ₁ -C ₃ Alkyl) NHC (=o), (C ₁ -C ₃ Alkyl group ₂ NC(＝O)、(C ₃ -C ₆ Cycloalkyl) NHC (=o), and (C ₃ -C ₆ Cycloalkyl) (C) ₁ -C ₃ Alkyl) NC (=o);

R ₇ independently selected from halogen, cyano, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₆ Cycloalkyl, (C) ₁ -C ₃ Alkyl) NHC (=o), (C ₁ -C ₃ Alkyl group ₂ NC(＝O)、(C ₃ -C ₆ Cycloalkyl) NHC (=o), and (C ₃ -C ₆ Cycloalkyl) (C) ₁ -C ₃ Alkyl) NC (=o), phenyl (which may be one to three independently selected from halogen, cyano, C ₁ -C ₄ Alkyl, C ₁ -C ₃ Alkoxy and C ₁ -C ₃ Haloalkyl), and a 6 membered heteroaromatic ring (which may be substituted with one to three substituents independently selected from halogen, cyano, C ₁ -C ₄ Alkyl, C ₁ -C ₃ Alkoxy and C ₁ -C ₃ Halo substituent).

2. The method of claim 1, wherein the diamide-resistant insect is from the order lepidoptera.

3. A method according to claim 1 or claim 2, wherein the diamide-resistant insect is resistant to at least one compound selected from the group consisting of: chlorantraniliprole, cyantraniliprole, cyclochlorantraniliprole, chlorfluazuron, tetrachlorethamide, tetrazolium chlorantraniliprole, flubendiamide and chlorfluazuron.

4. A method according to any one of claims 1 to 3, wherein the compound of formula I is represented by formula Ib, ic, id, ie, if or Ig:

wherein R is ₁ 、R ₃ 、R ₄ X1 and Z are as defined in claim 1.

5. The method according to any one of claims 1 to 4, wherein the diamide-resistant insect is plutella xylostella (Troczka et al 2012; steinbach et al 2015; guo et al 2014), tomato leaf miner (rotakis et al 2017; zimmer et al 2019), spodoptera frugiperda (Bolzan et al 2019), spodoptera exigua (Zuo et al 2020,2017), or chilo suppressalis (Yao et al 2017; yang et al 2017).

6. A method according to any one of claims 1 to 5, wherein the diamide-resistant insect is in a defined plant area/field, wherein the ratio of diamide-resistant insects to their respective sensitive lines is greater than 1:20 (based on the number of insects).

7. A method according to any one of claims 1 to 6, wherein the compound of formula I controls the diamide-resistant insect better than the secondary amide analogue of the compound of formula I.

8. The compound of claim 1 or claim 4, wherein such compound is excluded, (i) when R ₃ R in the case of 3-chloro-2-pyridinyl ₄ Is CF (CF) ₃ 、OCH ₂ CF ₃ 、Br、Cl、CHF ₂ 、OCF ₃ Or OCH ₃ The method comprises the steps of carrying out a first treatment on the surface of the And (ii) when R ₃ Is 3-chloro-2-pyridinyl and X1-Z is different from hydrogen, R ₄ Is OCHF ₂ 。

9. The compound of claim 8, wherein R ₁ Methyl, chlorine or bromine; r is R ₃ Is 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; r is R ₄ Is X2-Y (wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya 6); and X1 is a direct bond and Z is hydrogen, C ₁ -C ₃ Alkyl, C ₁ -C ₃ Haloalkyl, C ₃ -C ₄ Cycloalkyl, benzyl, or halobenzyl, and X1 is methylene and Z is C ₂ -C ₄ Alkenyl, C ₂ -C ₄ Alkynyl, C ₁ -C ₃ Alkoxy, C ₁ -C ₃ Haloalkoxy, or cyano.

10. The compound according to formula Ig of claim 4, wherein R ₁ Methyl, chlorine or bromine; r is R ₃ Is 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; r is R ₄ Is X2-Y (wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9), methoxy or OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the And X1 is a direct bond and Z is fluoro-.

11. The compound according to formula Ib according to claim 4, wherein R ₁ Methyl, chlorine or bromine; r is R ₃ Is 3-chloro-2-pyridinyl or 3, 5-dichloro-2-pyridinyl; r is R ₄ Is X2-Y (wherein X2 is CH ₂ Or CF (CF) ₂ And Y is selected from Ya1 to Ya6, and Ya 9), trifluoromethyl, methoxy or OCHF ₂ The method comprises the steps of carrying out a first treatment on the surface of the And X1 is a direct bond and Z is fluoro-.

12. A composition comprising a compound of formula I as defined in any one of claims 8 to 11, one or more adjuvants and diluents, and optionally one or more other active ingredients.

13. A method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula I as defined in any one of claims 8 to 11 or a composition as defined in claim 12.

14. A method for protecting plant propagation material from attack by insects, acarines, nematodes or molluscs which comprises treating the propagation material or the locus in which the propagation material is planted with an effective amount of a compound of formula I as defined in any one of claims 8 to 11 or a composition as defined in claim 12.

15. A plant propagation material, such as a seed, comprising a compound of formula I as defined in any one of claims 8 to 11 or a composition as defined in claim 12, or treated with the compound or the composition, or having the compound or the composition attached thereto.