JPWO2020250183A5 - - Google Patents

Description

The present invention relates to fused heterocyclic compounds. More particularly, the present invention relates to fused heterocyclic compounds of formula (I) and processes for their preparation. The invention further relates to the use of the fused heterocyclic compounds of formula (I) as pest control agents.

Modern insecticides and acaricides that are currently available must meet a number of requirements, e.g. with respect to level of efficacy, residual efficacy and spectrum of antimicrobial activity, as well as further beneficial effects and their possible uses. must. There have been dozens of efforts in the past to develop selective pesticides that act specifically on biochemical mechanisms of action that are only present in insects or mites, but that additionally exhibit in an advantageous manner different properties than known pesticides. been done over the years.

Heterocyclic compounds with control activity are known, e.g. Described.

However, the long-term use of such control agents has led many pests to develop resistance, making effective control increasingly difficult with existing insecticides and fungicides that have been used conventionally for many years. This phenomenon has increased further in recent years. In addition, some of these existing control agents are either highly toxic or persist in the environment for long periods due to their residual properties, which can become a serious problem due to ecosystem destruction.

Therefore, there is a continuing need for new compounds that are more effective, less toxic, environmentally safe and/or have different modes of action.

In view of the above, the present invention contemplates such compounds that meet or overcome the deficiencies associated with the prior art.

Surprisingly, it has now been found that certain novel fungically active fused heterocyclic compounds having sulfur-containing substituents which are the subject of the present invention have desirable properties as fungicides. rice field.

Accordingly, the present invention provides fused heterocyclic compounds of formula (I) or agriculturally acceptable salts, isomers/structural isomers, stereoisomers, diastereomers, enantiomers, tautomers, metal complexes thereof. , polymorphs, or N-oxides:

Formula (I)

[In the formula, R ¹ , Y, Q, A, G, m, and E are as defined in the detailed description].

In one embodiment, the invention provides a process for preparing a compound of formula (I) or an agriculturally acceptable salt thereof.

In another embodiment, the invention provides a composition for controlling or repelling invertebrate pests comprising a biologically effective amount of a compound of formula (I), an agriculturally acceptable salt thereof , isomers/structural isomers, stereoisomers, diastereomers, enantiomers, tautomers, metal complexes, polymorphs, or N-oxides thereof, and surfactants and auxiliaries. A composition is provided comprising one additional component.

In yet another embodiment, the composition comprises at least one selected from fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers, or nutrients. further comprising one additional biologically active compatible compound.

In yet another embodiment, the present invention provides a compound of formula (I), its agriculturally acceptable salts, isomers/ Structural isomers, stereoisomers, diastereomers, enantiomers, tautomers, metal complexes, polymorphs, or N-oxides, compositions, or combination uses are provided.

In yet another embodiment, the present invention provides a method of controlling an invertebrate pest, wherein the invertebrate pest grows or can grow in its habitat, breeding ground, food supply, plants, seeds, Soil, area, material, or environment, or material, plant, seed, soil, surface, or space to be protected from pest attack or infestation, is treated with a biologically effective amount of a compound of formula (I) or an agronomic its acceptable salts, isomers/structural isomers, stereoisomers, diastereomers, enantiomers, tautomers, metal complexes, polymorphs, or N-oxides, compositions, or combinations thereof Provide a method, including:

Definition:

The definitions provided herein for terms used in this disclosure are for illustrative purposes only and in no way limit the scope of the inventions disclosed in this disclosure.

As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having” ", "contains," "containing," "characterized by," or any other variation thereof encompasses non-exclusive inclusion subject to any express limitation. intended to be For example, compositions, mixtures, processes, or methods that include listed components are not necessarily limited to only those components, and compositions, mixtures, processes, or methods not explicitly listed or such compositions, mixtures, processes, or It may contain other components that are not method specific.

The transitional phrase “consisting of” excludes any element, step, or ingredient not specified. Claims, if any, are closed to the inclusion of materials other than those recited except for impurities normally associated therewith. When the phrase “consisting of” appears in a section of the body of a claim rather than immediately following the preamble, it limits only those elements listed in that section; Not excluded from scope.

The transitional phrase “consisting essentially of” refers to a composition or method that includes materials, steps, features, elements, or components in addition to those literally disclosed, provided that these additional materials, A step, feature, element, or component is used to define a composition or method that does not materially affect the basic and novel characteristics of the claimed invention. . The term "consisting essentially of" is neutral between "including" and "consisting of".

Further, unless expressly stated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, the condition A "or" B is satisfied by any of the following: A is 0 (or exists) and B is x (or does not exist), A is x (or does not exist) and B are true (or exist) and both A and B are true (or exist).

Also, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be nonrestrictive as to the number of instances (ie, occurrences) of the element or component. Thus, "a" or "an" should be read to include one or at least one, and the singular form of an element or component includes the plural unless the number is clearly meant to be singular. is also included.

As referred to in this disclosure, the term "invertebrate pest" includes arthropods, gastropods, and nematodes of economic importance as pests. The term "arthropods" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs, centipedes. The term "gastropod" includes snails, slugs and other stigma. The term "nematode" refers to organisms of the phylum Nematode. The term "helminth" includes roundworms, heartworms, phytophagous nematodes (Nematoda), flukes (Tematoda), hookworms, tapeworms ( rapeworm (Cestoda).

The term "agronomic" refers to the production of field crops such as food and fiber, corn, soybeans and other legumes, rice, cereals (e.g. wheat, oats, barley, rye, rice, maize), leafy vegetables (such as lettuce, cabbage, and other vegetable crops), fruiting vegetables (such as tomatoes, peppers, eggplants, cruciferous plants, and cucumbers), potatoes, sweet potatoes, Includes the growth of grapes, cotton, nuts (eg pears, drupes, citrus), small fruit trees (eg berries, cherries) and other specialty crops (eg canola, sunflowers, olives).

The term "nonagronomic" includes non-agricultural crops, e.g. and industrial structures, turf (e.g. turf farms, pastures, golf courses, lawns, sports fields, etc.), wood products, storage products, mixed agroforestry and vegetation management, public health (i.e. human) and animal health (eg, domesticated animals such as pets, farm animals, and poultry, non-domesticated animals such as wildlife) applications.

For non-agricultural uses, a parasiticidally effective (i.e., biologically effective) amount of the present invention, typically in the form of a composition formulated for veterinary use, is used. It includes protecting an animal from invertebrate parasites by administering the compound to the animal to be protected. As referred to in this disclosure and claims, the terms "parasiticidal" and "parasiticidally" refer to the observation of invertebrate parasitic pests to protect animals from pests. Point to possible effects. A parasiticidal effect typically relates to a reduction in the incidence or activity of a target invertebrate parasite. Such effects on pests include necrosis, death, retardation of growth, reduced mobility, or reduced ability to remain on or within the host animal, reduced feeding, and inhibition of reproduction. These effects on invertebrate parasites provide control (including prevention, reduction or elimination) of parasite infestations or infections in animals.

The compounds of the disclosure may exist in pure form or as mixtures of different possible isomeric forms, such as stereoisomers or structural isomers. Various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. . Any desired mixtures of these isomers are within the scope of the claims of this disclosure. One skilled in the art will appreciate that one stereoisomer may be more active and/or exhibit beneficial effects when enriched relative to other isomers or when separated from other isomers. you will understand. Furthermore, the person skilled in the art knows processes or methods or techniques for separating, enriching and/or selectively preparing said isomers.

The meaning of various terms used in this description will now be explained.

As used herein, the term "aliphatic compound" or "aliphatic group" is an organic compound in which carbon atoms are linked in straight, branched, or non-aromatic rings.

The term "alkyl", whether used alone or in compound words such as "alkylthio" or "haloalkyl" or -N(alkyl) or alkylcarbonylalkyl or alkylsulfonylamino, may be used in combination with linear or branched branched C ₁ ～C ₂₄ alkyl, preferably C ₁ ～C ₁₅ alkyl, more preferably C ₁ ～C ₁₀ alkyl, most preferably C ₁ ～C ₆ Contains alkyl. Representative examples of alkyl include methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3 -methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl , 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl , 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, and 1-ethyl-2-methylpropyl, or different isomers. When the alkyl is at the end of the compound substituent, e.g., alkylcycloalkyl, the portion of the compound substituent at the beginning, e.g., cycloalkyl, may be independently monosubstituted or polysubstituted, identical or different, by alkyl. may have been The same applies to compound substituents at the ends of other groups such as alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy, and the like.

The term "alkenyl", used either alone or in compound words, refers to a straight-chain or branched C ₂ ～C ₂₄ alkenes, preferably C ₂ ～C ₁₅ alkenes, more preferably C ₂ ～C ₁₀ alkenes, most preferably C ₂ ～C ₆ Contains alkenes. Representative examples of alkenes include ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-l-propenyl , 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3 -methyl-1-butenyl, l-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl -3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, l-ethyl-2-propenyl , 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1 -pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, l-methyl-3-pentenyl, 2-methyl-3-pentenyl , 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1 , 1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-l-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1 ,3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2 , 3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-l-butenyl, 3,3-dimethyl-2-butenyl, 1-ethyl-1-butenyl, 1-ethyl -2-butenyl, l-ethyl-3-butenyl, 2-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1 -ethyl-l-methyl-2-propenyl, l-ethyl-2-methyl-l-propenyl, and l-ethyl-2-methyl-2-propenyl, as well as different isomers. "Alkyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl. This definition also applies to alkenyl as part of compound substituents such as haloalkenyl, unless specifically defined otherwise.

The term "alkynyl" used either alone or in compound words refers to a straight or branched C ₂ ～C ₂₄ alkyne, preferably C ₂ ～C ₁₅ alkyne, more preferably C ₂ ～C ₁₀ alkyne, most preferably C ₂ ～C ₆ Contains alkynes. Non-limiting examples of alkynes include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3- pentynyl, 4-pentynyl, l-methyl-2-butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, 3-methyl-l-butynyl, 1,1-dimethyl-2-propynyl, 1- ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, l-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-l-pentynyl, 3-methyl-4-pentynyl, 4-methyl-l-pentynyl, 4-methyl-2-pentynyl, 1, 1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-l-butynyl, l- Included are ethyl-2-butynyl, l-ethyl-3-butynyl, 2-ethyl-3-butynyl, and l-ethyl-l-methyl-2-propynyl, as well as the different isomers. This definition also applies to compound substituents, such as alkynyl as part of haloalkynyl, and the like, unless specifically defined otherwise. The term "alkynyl" can also include moieties consisting of multiple triple bonds such as 2,5-hexadiynyl.

The term "cycloalkyl" means an alkyl closed to form a ring. Non-limiting examples include, but are not limited to cyclopropyl, cyclopentyl, and cyclohexyl. This definition also applies to cycloalkyl as part of compound substituents such as cycloalkylalkyl, etc., unless specifically defined otherwise.

The term "cycloalkenyl" means an alkenyl closed to form a ring containing a monocyclic partially unsaturated hydrocarbyl group. Non-limiting examples include, but are not limited to cyclopropenyl, cyclopentenyl, and cyclohexenyl. This definition also applies to cycloalkenyl as part of compound substituents such as cycloalkenylalkyl, unless specifically defined otherwise.

The term "cycloalkynyl" means an alkynyl closed to form a ring containing a monocyclic partially unsaturated group. Non-limiting examples include, but are not limited to cyclopropynyl, cyclopentynyl, and cyclohexynyl. This definition also applies to cycloalkynyl as part of compound substituents such as cycloalkynylalkyl, etc., unless specifically defined otherwise.

Terms such as "cycloalkoxy", "cycloalkenyloxy" are similarly defined. Non-limiting examples of cycloalkoxy include cyclopropyloxy, cyclopentyloxy, and cyclohexyloxy. This definition also applies to cycloalkoxy as part of compound substituents such as cycloalkoxyalkyl, etc., unless specifically defined otherwise.

The term "halogen" either alone or in compound words such as "haloalkyl" includes fluorine, chlorine, bromine or iodine. Additionally, when used in compound words such as "haloalkyl," said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Non-limiting examples of "haloalkyl" include chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1 -bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, 1,1-dichloro-2,2,2-trifluoroethyl, and 1,1,1-trifluoropropane -2-yl. This definition also applies to haloalkyl as part of compound substituents such as haloalkylaminoalkyl, etc., unless specifically defined otherwise.

The terms "haloalkenyl" and "haloalkynyl" are defined similarly except that alkenyl and alkynyl groups are present as part of the substituent instead of alkyl groups.

The term "haloalkoxy" means a straight or branched chain alkoxy group in which some or all of the hydrogen atoms of the group may be replaced with halogen atoms as specified above. Non-limiting examples of haloalkoxy include chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-fluoroethoxy, 2-chloro-2,2-difluoro Included are ethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2-trichloroethoxy, pentafluoroethoxy, and 1,1,1-trifluoroprop-2-oxy. This definition also applies to haloalkoxy as part of compound substituents such as haloalkoxyalkyl, etc., unless specifically defined otherwise.

The term "haloalkylthio" means a straight or branched chain alkylthio group wherein some or all of the hydrogen atoms of the group may be replaced with halogen atoms as specified above. Non-limiting examples of haloalkylthio include chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio, dichlorofluoromethylthio, chlorodifluoromethylthio, 1-chloroethylthio , 1-bromoethylthio, 1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2-fluoroethylthio, 2- chloro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethylthio, and 1,1,l-trifluoroprop-2- Ilthio is included. This definition also applies to haloalkylthio as part of compound substituents such as haloalkylthioalkyl, unless otherwise specifically defined.

Non-limiting examples of "haloalkylsulfinyl" include CF ₃ S(O), CCl ₃ S(O), CF ₃ CH ₂ S(O), and CF ₃ CF ₂ S(O) is included. Examples of "haloalkylsulfonyl" include CF ₃ S(O) ₂ , CCl ₃ S(O) ₂ , CF ₃ CH ₂ S(O) ₂ , and CF ₃ CF ₂ S(O) ₂ is included.

The term "hydroxy" means -OH and amino means -NRR, where R can be any possible substituent such as H or alkyl. Carbonyl means -C(O)-, carbonyloxy means -OC(O)-, sulfinyl means SO, sulfonyl means S(O) ₂ means

The term "alkoxy", used either alone or in compound words, includes C ₁ ～C ₂₄ alkoxy, preferably C ₁ ～C ₁₅ alkoxy, more preferably C ₁ ～C ₁₀ alkoxy, most preferably C ₁ ～C ₆ Contains alkoxy. Examples of alkoxy include methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3- methylbutoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4 -methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethyl butoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy, and l-ethyl-2-methylpropoxy, and different isomers. be This definition also applies to alkoxy as part of compound substituents such as haloalkoxy, alkynylalkoxy, and the like, unless specifically defined otherwise.

The term "alkoxyalkyl" denotes alkoxy substitution on alkyl. Non-limiting examples of "alkoxyalkyl" include CH ₃ OCH ₂ , CH ₃ OCH ₂ CH ₂ , CH ₃ CH ₂ OCH ₂ , CH ₃ CH ₂ CH ₂ CH ₂ OCH ₂ , and CH ₃ CH ₂ OCH ₂ CH ₂ is included.

The term "alkoxyalkoxy" denotes alkoxy substitution on alkoxy.

The term "alkylthio" refers to branched or straight chain alkylthio moieties such as methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio, 1,1-dimethyl ethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2 -dimethylpropylthio, 1-methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethyl butylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1 , 2,2-trimethylpropylthio, 1-ethyl-1-methylpropylthio, and l-ethyl-2-methylpropylthio, as well as different isomers.

Halocycloalkyl, halocycloalkenyl, alkylcycloalkyl, cycloalkylalkyl, cycloalkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylcarbonyl, cycloalkylcarbonyl, haloalkoxyalkyl and the like are defined analogously to the above examples. .

The term "alkylthioalkyl" means alkylthio substitution on alkyl. Representative examples of "alkylthioalkyl" include -CH ₂ SCH ₂ , -CH ₂ SCH ₂ CH ₂ , CH ₃ CH ₂ SCH ₂ , CH ₃ CH ₂ CH ₂ CH ₂ SCH ₂ , and CH ₃ CH ₂ SCH ₂ CH ₂ is included. "Alkylthioalkoxy" denotes alkylthio substitution on alkoxy. The term "cycloalkylalkylamino" denotes cycloalkyl substitution on alkylamino.

Terms such as alkoxyalkoxyalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkylaminoalkyl, cycloalkylaminocarbonyl are defined similarly as "alkylthioalkyl" or cycloalkylalkylamino.

The term "alkoxycarbonyl" is an alkoxy group attached to the backbone through a carbonyl group (-CO-). This definition also applies to alkoxycarbonyl as part of compound substituents such as cycloalkylalkoxycarbonyl and the like, unless specifically defined otherwise.

The term "alkoxycarbonylalkylamino" denotes alkoxycarbonyl substitution on alkylamino. "Alkylcarbonylalkylamino" denotes alkylcarbonyl substitution on alkylamino. Terms such as alkylthioalkoxycarbonyl, cycloalkylalkylaminoalkyl and the like are similarly defined.

Non-limiting examples of "alkylsulfinyl" include methylsulfinyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, butylsulfinyl, 1-methylpropylsulfinyl, 2-methylpropylsulfinyl, 1,1-dimethylethylsulfinyl , pentylsulfinyl, 1-methylbutylsulfinyl, 2-methylbutylsulfinyl, 3-methylbutylsulfinyl, 2,2-dimethylpropylsulfinyl, 1-ethylpropylsulfinyl, hexylsulfinyl, 1,1-dimethylpropylsulfinyl, 1,2 -dimethylpropylsulfinyl, 1-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methylpentylsulfinyl, 4-methylpentylsulfinyl, 1,1-dimethylbutylsulfinyl, 1,2-dimethylbutylsulfinyl, 1,3-dimethyl Butylsulfinyl, 2,2-dimethylbutylsulfinyl, 2,3-dimethylbutylsulfinyl, 3,3-dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1 , 2,2-trimethylpropylsulfinyl, 1-ethyl-1-methylpropylsulfinyl, and 1-ethyl-2-methylpropylsulfinyl, and different isomers. The term "arylsulfinyl" includes Ar-S(O), where Ar can be any carboxyl or heterocycle. This definition also applies to alkylsulfinyl as part of compound substituents such as haloalkylsulfinyl, unless specifically defined otherwise.

Non-limiting examples of "alkylsulfonyl" include methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, 1,1-dimethylethylsulfonyl , pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonyl, 3-methylbutylsulfonyl, 2,2-dimethylpropylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, 1,1-dimethylpropylsulfonyl, 1,2 -dimethylpropylsulfonyl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentylsulfonyl, 1,1-dimethylbutylsulfonyl, 1,2-dimethylbutylsulfonyl, 1,3-dimethyl Butylsulfonyl, 2,2-dimethylbutylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, 1-ethylbutylsulfonyl, 2-ethylbutylsulfonyl, 1,1,2-trimethylpropylsulfonyl, 1 , 2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropylsulfonyl, and l-ethyl-2-methylpropylsulfonyl, and different isomers. The term "arylsulfonyl" refers to Ar-S(O) ₂ wherein Ar can be any carboxyl or heterocyclic ring. This definition also applies to compound substituents such as alkylsulfonyl as part of alkylsulfonylalkyl and the like, unless otherwise defined.

"Alkylamino", "dialkylamino" and the like are defined analogously to the examples above.

The term "carbocycle" includes "aromatic carbocyclic ring system" and "non-aromatic carbocyclic ring system" or polycyclic or bicyclic ring systems in which the rings may be aromatic or non-aromatic. (spiro, fused, bridged, non-fused) ring compounds (aromatic indicates that Hückel rule is satisfied, non-aromatic indicates that Hückel rule is not satisfied).

The term "hetero" in reference to rings means that at least one ring atom is not carbon and contains 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. (where each ring contains up to 4 nitrogens, up to 2 oxygens, and up to 2 sulfurs).

The term "aromatic" indicates that the Hückel rule is satisfied, and the term "non-aromatic" indicates that the Hückel rule is not satisfied.

The term "heterocycle" or "heterocyclic" or "heterocyclic ring system" means "aromatic heterocycle" or "heteroaryl bicyclic ring system" and "non-aromatic heterocyclic ring system", or polycyclic or bicyclic (spiro, fused, bridged, non-fused) ring compounds in which the rings may be aromatic or non-aromatic, wherein heterocycle is N, O, S (O ) _0-2 and/or C ring members of the heterocyclic ring are C(=O), C(=S), C(=CR ^* R. ^* ), and C=NR ^* may be replaced by ^* indicates an integer.

The term "non-aromatic heterocycle" or "non-aromatic heterocyclic" means: 3-15 membered containing 1-4 heteroatoms from the group of oxygen, nitrogen and sulfur; preferably 3- to 12-membered saturated or partially unsaturated heterocyclic ring: in addition to the carbon ring members, 1 to 3 nitrogen atoms and/or 1 oxygen or sulfur atom or 1 or 2 oxygen and/or or a monocyclic, bicyclic, or tricyclic heterocyclic ring containing a sulfur atom (when the ring contains more than one oxygen atom, they are not directly adjacent); oxetanyl, oxiranyl, aziridinyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-isoxazolidinyl , 4-isoxazolidinyl, 5-isoxazolidinyl, 3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl, 1-pyrazolidinyl, 3-pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 1-imidazolidinyl, 2-imidazolidinyl, 4-imidazolidinyl, 1,2,4-oxadiazolidine- 3-yl, 1,2,4-oxadiazolidin-5-yl, 1,2,4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl, 1,2, 4-triazolidin-1-yl, 1,2,4-triazolidin-3-yl, 1,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin-2-yl, 1, 3,4-triazolidin-1-yl, 1,3,4-triazolidin-2-yl, 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl, 2,4-dihydrofur -2-yl, 2,4-dihydrofur-3-yl, 2,3-dihydrothien-2-yl, 2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl, 2 , 4-dihydrothien-3-yl, pyrrolinyl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 2-isoxazolin-3- yl, 3-isoxazolin-3-yl, 4-isoxazolin-3-yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4-isoxazolin-4-yl, 2-isoxazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3- isothiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3-dihydropyrazol-l-yl, 2 ,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazole- l-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4-yl, 3,4-dihydropyrazol-5-yl, 4,5-dihydropyrazol-l-yl, 4, 5-dihydropyrazol-3-yl, 4,5-dihydropyrazol-4-yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydroxazol-3 -yl, 2,3-dihydrooxazol-4-yl, 2,3-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4 -dihydrooxazol-4-yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4- yl, piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, pyrazinyl, morpholinyl, thiomorphulinyl, 1,3-dioxan-5-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, 3 -hexahydropyridazinyl, 4-hexahydropyridazinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl, 1,3,5-hexahydrotriazine-2 -yl, 1,2,4-hexahydrotriazin-3-yl, cycloserine, 2,3,4,5-tetrahydro[1H]azepine-1- or -2- or -3- or -4- or -5 - or -6- or -7-yl, 3,4,5,6-tetra-hydro[2H]azepin-2- or -3- or -4- or -5- or -6- or -7-yl , 2,3,4,7-tetrahydro[1H]azepin-1- or -2- or -3- or -4- or -5- or -6- or -7-yl, 2,3,6,7 - tetrahydro[1H]azepine-1- or -2- or -3- or -4- or -5- or -6- or -7-yl, hexahydroazepine-1- or -2- or -3- or -4-yl, tetra-, and hexahydrooxepinyl, such as 2,3,4,5-tetrahydro[1H]oxepin-2- or -3- or -4- or -5- or -6- or -7-yl, 2,3,4,7-tetrahydro[1H]oxepin-2- or -3- or -4- or -5- or -6- or -7-yl, 2,3,6,7 - tetrahydro[1H]oxepin-2- or -3- or -4- or -5- or -6- or -7-yl, hexahydroazepin-1- or -2- or -3- or -4-yl , tetra- and hexahydro-1,3-diazepinyl, tetra- and hexahydro-1,4-diazepinyl, tetra- and hexahydro-1,3-oxazepinyl, tetra- and hexahydro-1,4-oxazepinyl, tetra- and hexahydro- 1,3-dioxepinyl, tetra- and hexahydro-1,4-dioxepinyl. This definition also applies to heterocyclyl as part of compound substituents such as heterocyclylalkyl, unless specifically defined otherwise.

The term "heteroaryl" or "heteroaromatic" means: a 5- or 6-membered fully unsaturated ring containing 1-4 heteroatoms from the group of oxygen, nitrogen, and sulfur. monocyclic ring system (, if the ring contains more than one oxygen atom, they are not directly adjacent): 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms and 1 sulfur or 5-membered heteroaryl containing an oxygen atom: in addition to carbon atoms, a 5-membered heteroaryl group optionally containing 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms and 1 sulfur or oxygen atom as ring members , such as (but not limited to) furyl, thienyl, pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,4 -triazolyl, 1,3,4-oxadiazolyl, 1,3,4-thiadiazolyl, 1,3,4-triazolyl, tetrazolyl; nitrogen-bonded 5-membered heteroaryl containing 1 to 4 nitrogen atoms, or 1 to 3 benzo-fused nitrogen-bonded 5-membered heteroaryl containing a nitrogen atom: a 5-membered heteroaryl group optionally containing 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms as ring members in addition to carbon atoms buta-1,3- wherein 2 adjacent carbon ring members or 1 nitrogen and 1 adjacent carbon ring member may be replaced with 1 or 2 carbon atoms by nitrogen atoms; Optionally bridged by diene-1,4-diyl groups, these rings being attached to the backbone through one of the nitrogen ring members, 5-membered heteroaryl groups such as (but not limited to 1-pyrrolyl, 1-pyrazolyl, 1,2,4-triazol-l-yl, 1-imidazolyl, 1,2,3-triazol-1-yl, and 1,3,4-triazol-1 - Ill.

6-membered heteroaryl containing 1 to 4 nitrogen atoms: in addition to carbon atoms, for example, 6-membered heteroaryl groups which may contain, for example, 1 to 3 and 1 to 4 nitrogen atoms as ring members, respectively; For example (without limitation) 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3, 5-triazin-2-yl, 1,2,4-triazin-3-yl, and 1,2,4,5-tetrazin-3-yl; 1 to 3 nitrogen atoms or 1 nitrogen atom and 1 Benzo-fused 5-membered heteroaryl containing one oxygen or sulfur atom: for example (but not limited to) indol-l-yl, indol-2-yl, indol-3-yl, indol-4-yl, indole -5-yl, indol-6-yl, indol-7-yl, benzimidazol-l-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, indazol-l-yl , indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indazol-7-yl, indazol-2-yl, l-benzofuran-2-yl, l-benzofuran-3 -yl, l-benzofuran-4-yl, l-benzofuran-5-yl, 1-benzofuran-6-yl, l-benzofuran-7-yl, l-benzothiophen-2-yl, l-benzothiophene-3 -yl, l-benzothiophen-4-yl, 1-benzothiophen-5-yl, l-benzothiophen-6-yl, l-benzothiophen-7-yl, 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl, 1,3-benzothiazol-7-yl, 1,3-benzoxazole -2-yl, 1,3-benzoxazol-4-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl, and 1,3-benzoxazol-7-yl; Benzo-fused 6-membered heteroaryl containing 1-3 nitrogen atoms: for example (but not limited to) quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5-yl, quinoline -6-yl, quinolin-7-yl, quinolin-8-yl, isoquinolin-l-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7 -yl, and isoquinolin-8-yl.

This definition also applies to heteroaryl as part of compound substituents such as heteroarylalkyl, unless specifically defined otherwise.

The term "trialkylsilyl" refers to three branched and/or straight chain alkyl groups attached to and linked through a silicon atom such as trimethylsilyl, triethylsilyl, and t-butyl-dimethylsilyl. include. "Halotrialkylsilyl" indicates that at least one of the three alkyl groups is partially or fully substituted with halogen atoms which may be the same or different. The term "alkoxytrialkylsilyl " indicates that at least one of the three alkyl groups has been substituted with one or more alkoxy groups which may be the same or different. The term "trialkylsilyloxy" denotes a trialkylsilyl moiety attached through an oxygen.

Non-limiting examples _of "alkylcarbonyl" include C(O) _CH3 , C(O) _{CH2CH2CH3 ,} and C(O)CH( _CH3 ) ₂ . Non-limiting examples of "alkoxycarbonyl" include _CH3OC (=O), _{CH3CH2OC (} =O) _{, CH3CH2CH2OC} (=O), ( _{CH3 ) 2CHOC} ( =O), and different butoxy- or pentoxycarbonyl isomers. Non-limiting _{examples of "alkylaminocarbonyl" include CH3NHC(=O), CH3CH2NHC ( = O )} , _CH3CH2CH2NHC (=O), ( _CH3 ) _2CHNHC (=O), and different butylamino- or pentylaminocarbonyl isomers. Non-limiting examples of _" dialkylaminocarbonyl" include ( _CH3 ) _2NC (=O ₎ , ( _CH3CH2 ) _2NC (=O), _CH3CH2 ( _CH3 )NC(=O ), _CH3CH2CH2 ( _CH3 )NC(=O) _, and ( _CH3 ) _2CHN ( _CH3 ) _C (=O). Non-limiting examples _{of " alkoxyalkylcarbonyl" include CH3OCH2C (} = _O ), _CH3OCH2CH2C (=O), _CH3CH2OCH2C (=O) _{, CH3 Included are CH2CH2CH2OCH2C (} =O) and _{CH3CH2OCH2CH2C ( =} O) _. Non-limiting examples _{of " alkylthioalkylcarbonyl "} include _CH3SCH2C (= _O ), _CH3SCH2CH2C (=O), _CH3CH2SCH2C (=O), _{CH3 CH2CH2CH2SCH2C (} =O ₎ and _{CH3CH2SCH2CH2C ( =} O) are _{included .} Terms such as haloalkylsulfonylaminocarbonyl, alkylsulfonylaminocarbonyl, alkylthioalkoxycarbonyl, alkoxycarbonylalkylamino are similarly defined.

Non-limiting _{examples of} "_{alkylaminoalkylcarbonyl" include CH3NHCH2C (} = _{O )} , _CH3NHCH2CH2C (=O), _CH3CH2NHCH2C (=O), CH _{3CH2CH2CH2NHCH2C (} =O _{) , and CH3CH2NHCH2CH2C (} = _O ) _.

The term "amido" means A-R'C=ONR''-B, where R' and R'' represent substituent groups and A and B represent optional groups.

The term "thioamide" means A-R'C=SNR''-B, where R' and R'' represent substituent groups and A and B represent optional groups.

The total number of carbon atoms in a substituent is indicated by the prefix “C _i -C _j ”, where i and j are numbers from 1-21. For example, C ₁ -C ₃ alkylsulfonyl denotes methylsulfonyl to propylsulfonyl, C ₂ alkoxyalkyl denotes CH ₃ OCH ₂ , C ₃ alkoxyalkyl denotes, for example, CH ₃ CH(OCH ₃ ), CH ₃ OCH ₂ CH ₂ , or CH ₃ CH ₂ OCH ₂ , C ₄ alkoxyalkyl denotes various isomers of an alkyl group substituted with an alkoxy group containing a total of 4 carbon atoms, examples include CH _{3 CH2CH2OCH2 , and CH3CH2OCH2CH2 . _ _} In the above description, when compounds of formula (I) consist of one or more heterocycles, all substituents may be substituted via any available carbon or nitrogen by replacing a hydrogen on said carbon or nitrogen. are attached to these rings.

When compounds are substituted with substituents with subscripts indicating that the number of said substituents can be greater than 1, the substituents (if they are greater than 1) are selected from the group of substituents specified independently selected. Further, when the subscript m of (R) _m indicates an integer ranging from 0-4, for example, the number of substituents may be selected from integers ranging from 0-4.

When a group contains a substituent which may be hydrogen, it is recognized that the group is unsubstituted if the substituent is hydrogen.

Embodiments herein and various features and advantageous details thereof are described with reference to non-limiting embodiments in this description. Descriptions of well-known components and processing techniques are omitted so as not to unnecessarily obscure the embodiments herein. The examples used herein are merely intended to facilitate an understanding of how the embodiments herein may be practiced and to further enable those skilled in the art to practice the embodiments herein. are doing. Therefore, the examples should not be construed as limiting the scope of the embodiments herein.

The description of specific embodiments sufficiently reveals the general nature of the embodiments herein that others may, by applying their current knowledge, without departing from the general concept. , such specific embodiments may be readily modified and/or adapted for various uses, and such adaptations and modifications are therefore contemplated within the meaning and range of equivalents of the disclosed embodiments. should be and are intended to be. It is to be understood that the terminology or terminology used herein is for the purpose of description and should not be regarded as limiting. Thus, although the embodiments herein have been described with respect to preferred embodiments, those skilled in the art will appreciate that the embodiments herein can be modified and practiced within the spirit and scope of the embodiments described herein. would recognize

Any discussion of any documents, acts, materials, devices, articles, etc., contained herein is for the sole purpose of providing a context for disclosure. Any or all of these matters may have existed prior to the priority date of the present application and thus form part of the basis of the prior art or are common knowledge in the field to which this disclosure pertains. should not be taken as an admission that

While the numerical values set forth in the present description and the description/claims may form an essential part of the invention, any deviation from such numerical values may constitute the invention disclosed herein. is still within the scope of the invention if it follows the same scientific principles as those of The compounds of the invention according to the invention also exist where appropriate as mixtures of the different possible isomeric forms, in particular as mixtures of stereoisomers, for example E and Z, threo and erythro, and as mixtures of optical isomers. obtained, but may exist as a mixture of tautomers where appropriate. Both the E and Z isomers, as well as the threo- and erythro isomers, as well as the optical isomers, any desired mixtures of these isomers and the possible tautomers are disclosed and claimed.

The term "pest" for the purposes of this disclosure includes, but is not limited to, fungi, stramenopiles (oomycetes), bacteria, nematodes, mites, ticks, insects, and rodents. is not limited to Pests are also plants and animals that are harmful to humans or human concerns, including crops, livestock, and forestry.

The term "plant" is understood herein to mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants may be plants obtainable by conventional breeding and optimization methods, or biotechnological and genetic engineering methods, or a combination of these methods, transgenic plants and at the discretion of the plant breeder. Includes protectable and non-protectable plant cultivars.

For the purposes of this disclosure, the term "plant" typically refers to trees, shrubs that grow in a location, absorb water and necessary substances through their roots, and synthesize nutrients in their leaves through photosynthesis. , herbs, lawns, ferns, and mosses.

Examples of "plants" for the purposes of the present invention include agricultural crops such as wheat, rye, barley, triticale, oats, or rice; beets, such as sugar beets or fodder beets; fruits and fruit trees; pome fruit, drupe or soft fruit such as apple, pear, plum, peach, almond, cherry, strawberry, raspberry, blackberry or gooseberry; legumes such as lentils, peas, alfalfa, soybean; oil plant such as rapeseed, mustard, olive, sunflower, coconut, cocoa bean, castor bean, oil palm, peanut, or soybean; cucurbit, such as pumpkin, cucumber, or melon; fiber Plants such as cotton, flax, hemp, or jute: citrus fruits and citrus trees, such as oranges, lemons, grapefruits, or mandarins; any garden plants, vegetables, such as spinach, lettuce, asparagus, cabbage , carrots, onions, tomatoes, potatoes, gourds or paprika; Lauraceae plants such as avocado, cinnamon or camphor; cucurbitaceae; oleaginous plants; energy and feedstock plants such as grains , corn, soybeans, other legumes, rapeseed, sugarcane, or oil palm; tobacco; nuts; coffee; tea; sweet leaves (also called stevia); gum plants or ornamental and forest plants such as flowers, shrubs, broadleaf or evergreens such as conifers; plant propagation material such as seeds and crops of these plants Materials include, but are not limited to.

Preferably, plants for the purposes of the present invention include cereals, maize, rice, soybeans and other legumes, fruits and fruit trees, grapes, nuts and nut trees, citrus fruits and citrus trees, any horticultural plants, cucurbits, oil-bearing plants, tobacco, coffee, tea, cocoa, sugar cane, sugar beets, cotton, potatoes, tomatoes, onions, peppers, and vegetables, ornamental plants, any floricultural plants, and humans and Other plants for animal use include, but are not limited to.

The term "plant part" is understood to mean all parts and organs of plants above ground and below ground. For the purposes of this disclosure, the term plant part includes roots including cuttings, leaves, twigs, tubers, flowers, seeds, branches, taproots, lateral roots, root hairs, apexes, crowns, rhizomes, grafts. (slip), shoots, fruits, fruit bodies, bark, stems, buds, axillary buds, meristems, nodes and internodes.

The term "the locus" includes the soil, the surroundings of the plant or plant part, and equipment or implements used before, during or after sowing/planting the plant or plant part.

Application of the compounds of the disclosure, or optionally other compatible compounds, in compositions containing the compounds of the disclosure, or to the locus of plants or plant material, includes spraying, coating, dipping, fumigating, impregnating, injecting, and application by techniques known to those skilled in the art, including but not limited to dusting.

The term "applied" means physically or chemically attaching to a plant or plant part, including impregnation.

In one embodiment, the present invention provides compounds of formula (I):

Formula (I)

[In the formula,
R ¹ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ -C ₈ -cycloalkyl, and _C3 - _C8 -cycloalkyl- _C1 - _C6 -alkyl,
Y is independently selected from O or NR ^Y ;
R ^Y is hydrogen, cyano, C ₁ -C ₄ -alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, C ₁ -C ₄ -haloalkyl, C ₂ -C ₄ -haloalkenyl, C ₃ -C ₅ -cycloalkyl, and C ₃ -C ₅ -cycloalkyl-C ₁ -C ₃ -alkyl,
A represents N or ^CR2 ,
G represents N or C, provided that both G are not nitrogen at the same time,
R ² is hydrogen, halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl , C ₃ -C ₈ -cycloalkyl, OR ⁴ , CR ⁴ =NR ⁵ , NR ⁵ R ⁶ , S(O) _0-2 R ⁷ , C(=O)R ⁸ , S(O) _0-1 R ⁹ =NR ¹⁰ , N=S(O) _0-1 (R ⁹ ) ₂ , P(=O)(OR') ₂ , Si(R') ₃ , C _{6 -C 10} -aryl, C _{7 -C 14} -aralkyl, and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group optionally substituted with one or more R ^2a groups, a cyclic group of R ² is optionally substituted with one or more R ^2b groups,
R ^2a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ⁴ , ^CR4 = ^NR5 , ^NR5R6 , S( ^O ) _0-2R7 , C(=O) ^R8 , S( ^O ) _0-1R9 = ^NR10 , N=S( ^O ) _0-1 (R ⁹ ) ₂ , Si(R′) ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl;
R ^2b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl _{, OR4, CR4=NR5, NR5R6, S(O)0-2R7} ^{, C ( = O} ) ^{R8 ,} Si(R') ₃ , S(O ) _0-1 R ⁹ =NR ¹⁰ and N=S(O) _0-1 (R ⁹ ) ₂ , or two R ^2a or two R ^2b substituents are C(=O), C(=S), S(O) _0-2 , and 1-3 ring members selected from the group consisting of Si(R′) ₂ may optionally be included to form a 3-7 membered ring, said 3-7 membered ring comprising optionally substituted with one or more R ^2ab groups,
R ^2ab is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ -C ₈ -cycloalkyl, OR ⁴ , NR ⁵ R ⁶ , S(O) _0-2 R ⁷ , S(O) _0-1 R ⁹ =NR ¹⁰ , N=S(O) _0-1 (R ⁹ ) selected from the group consisting of ₂ , Si(R′) ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl;
Q represents a partially saturated or unsaturated 5- to 12-membered heterocyclic ring system optionally substituted with one or more R ³ groups, said heterocyclic ring system comprising unsubstituted benzothiazolyl and does not represent unsubstituted N-methylbenzimidazolyl,
R ³ is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, ^OR4 , ^CR4 = ^NR5 _, ^NR5R6 , S(O) ^0-2R7 , C(= ^O ) ^R8 , S(O) ^0-1R9 ₌ NR ¹⁰ , N=S(O) _0-1 (R ⁹ ) ₂ , P(=O)(OR') ₂ , Si(R') ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ - aralkyl, and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group optionally substituted with one or more R ^3a groups, wherein the cyclic group of R ³ is optionally substituted with one or more R ^3b groups,
R ^3a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ⁴ , ^CR4 = ^NR5 , ^NR5R6 , S( ^O ) _0-2R7 , C(=O) ^R8 , S( ^O ) _0-1R9 = ^NR10 , N=S( ^O ) _0-1 (R ⁹ ) ₂ , Si(R′) ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl;
R ^3b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -Cycloalkyl, ^{OR4 ,} C(R') ₂ - ^NR5R6 , C(R') _2- OR4, ^CR4 = ^NR5 , ^{NR5R6 ,} S(O ⁾ _{0- 2} R ⁷ , C(=O)R ⁸ , S(O) _0-1 R ⁹ =NR ¹⁰ , N=S(O) _0-1 (R ⁹ ) ₂ , Si(R') ₃ , C ₆ ~ selected from the group consisting of C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl;
Two R ^3a or two R ^3b substituents, together with the atom to which they are attached, or together with a further atom selected from the group consisting of C, N, O, S, are C (=O ), C(=S), S(O) _m , and Si(R′) ₂ to form a 3-7 membered ring, optionally containing 1-3 ring members selected from the group consisting of and said 3- to 7-membered ring may be optionally substituted on that moiety with one or more R ^3ab groups, wherein R ^3ab is hydrogen, halogen, cyano, C ₁ -C ₆ -alkyl, C ₁ ^- _C6 -haloalkyl, _C3 - _C8 -cycloalkyl, ^OR4 , ^NR5R6 , S( ^O ) _0-2R7 ,
two R ³ together with the atom to which they are attached or together with a further atom selected from the group consisting of C, N, O, S are C(=O), C(=S) , S(O) _m , and Si(R′) ₂ , optionally containing 1 to 3 ring members selected from the group consisting of 3 to 7 membered rings, wherein the 3 to 7-membered ring for that moiety is one or more selected from the group consisting of halogen, cyano, R ^3c , OR ^3c , SR ^3c , NR ^3c ₂ , Si(R ^3c ) ₃ , COOR ^3c , and CONR ^3c ₂ may be substituted with a group of
R ^3c is selected from the group consisting of hydrogen, halogen, linear or branched C ₁ -C ₆ -alkyl, and cyclic C _3-8 -alkyl, each group of R ^3c being one or more halogen is optionally replaced with
Ring E represents a 5- or 6-membered heterocyclic ring fused to Ring D, wherein Ring E is optionally substituted by one or more R ¹¹ groups;
R ¹¹ is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, ^OR4 , ^CR4 = ^NR5 _, ^NR5R6 , S(O) ^0-2R7 , C(= ^O ) ^R8 , S(O) ^0-1R9 ₌ NR ¹⁰ , N=S(O) _0-1 (R ⁹ ) ₂ , P(=O)(OR') ₂ , Si(R') ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ - aralkyl, and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group optionally substituted with one or more R ^11a groups, the cyclic group of R ¹¹ being optionally substituted with one or more R ^11b groups,
R ^11a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ⁴ , ^CR4 = ^NR5 , ^NR5R6 , S( ^O ) _0-2R7 , C(=O) ^R8 , S( ^O ) _0-1R9 = ^NR10 , N=S( ^O ) _0-1 (R ⁹ ) ₂ , Si(R′) ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl;
R ^11b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -Cycloalkyl, ^{OR4 ,} C(R') ₂ - ^NR5R6 , C(R') _2- OR4, ^CR4 = ^NR5 , ^{NR5R6 ,} S(O ⁾ _{0- 2} R ⁷ , C(=O)R ⁸ , S(O) _0-1 R ⁹ =NR ¹⁰ , N=S(O) _0-1 (R ⁹ ) ₂ , Si(R') ₃ , C ₆ ~ selected from the group consisting of C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl;
R ⁴ is hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - selected from the group consisting of C ₈ -cycloalkyl, S(O) ₂ R ⁷ , Si(R′) ₃ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl and C ₃ -C ₁₀ -heterocyclyl; , each aliphatic group is optionally substituted with R ^4a , the cyclic group of R ⁴ is optionally substituted with one or more R ^4b groups,
R ^4a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ', NR'R'', S(O) _0-2R ', C(=O)R', Si(R') ₃ , _C6 - _C10 -aryl, _C7 - _C14 -aralkyl, and is selected from the group consisting of C ₃ -C ₁₀ -heterocyclyl,
R ^4b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, OR, NR'R'', S(O) _0-2R ', C(=O)R', Si(R') ₃ , _C6 -Cio _- aryl, C ₇ -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl',
R ⁵ is hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -Cycloalkyl, ^OR4 , NR'R'^' , S(O) _0-2R7 , C(=O) ^R8 , Si(R') ₃ , _C6 - _C10 -aryl, _C7 -C ₁₄ -aralkyl, and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group optionally substituted with R ^5a and the cyclic group of R ⁵ being one or optionally substituted with multiple R ^5b groups,
R ^5a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ', NR'R'', S(O) _0-2R ', C(=O)R', Si(R') ₃ , _C6 - _C10 -aryl, _C7 - _C14 -aralkyl, and is selected from the group consisting of C ₃ -C ₁₀ -heterocyclyl,
R ^5b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, OR', NR'R'', S(O) _0-2R ', Si(R') ₃ , C(=O)R', _C6 -Cio _- aryl, selected from the group consisting of C ₇ -C ₁₄ -aralkyl and C ₃ -C ₁₀ -heterocyclyl;
R ⁶ is hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₁ - selected from the group consisting of C ₆ -cycloalkyl, and C(=O)R ⁸ ;
R ⁷ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ -C ₈ -cycloalkyl, NR ⁵ R ⁶ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group comprising one or more optionally substituted with R ^7a groups, the cyclic group of R ⁷ optionally substituted with one or more R ^7b groups,
R ^7a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ', NR'R'', S(O) _0-2R ', C(=O)R', C6 _{- C10} -aryl, _C7 - _C14 -aralkyl and _C3 - _C10 -heterocyclyl is selected from the group consisting of
R ^7b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, OR', NR'R'', S(O) _0-2R ', C(=O)R', _C6 - _C10 -aryl, _C7 - _C14 -aralkyl , and C ₃ -C ₁₀ -heterocyclyl,
R ⁸ is hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - C ₈ -cycloalkyl, OR ⁴ , NR ⁵ R ⁶ , N=S(O) _0-1 (R ⁹ ) ₂ , C ₆ -C ₁₀ -aryl, C ₇ -C ₁₄ -aralkyl and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group optionally substituted with one or more R ^8a groups, the cyclic group of R ⁸ being one or more R ^8b groups optionally substituted with
R ^8a is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ', NR'R'', S(O) _0-2R ', C(=O)R', C6 _{- C10} -aryl, _C7 - _C14 -aralkyl and _C3 - _C10 -heterocyclyl is selected from the group consisting of
R ^8b is halogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, OR', NR'R'', S(O) _0-2R ', C(=O)R', _C6 - _C10 -aryl, _C7 - _C14 -aralkyl , and C ₃ -C ₁₀ -heterocyclyl,
R ⁹ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ -C ₈ -cycloalkyl, and C(=O) ^R8 ;
R ¹⁰ is hydrogen, cyano, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ - _C8 -cycloalkyl, Si(R') ₃ , S(O) _0-2R7 , and C(= ^O ) ^R8 ;
R' is halogen, cyano, R'', OR'', N(R'') ₂ , S(O) _0-2 R'', C(=O)R'', C(=O)OR '', and C(=O)N(R'') ₂ R ⁸ ;
R'' consists of hydrogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl and C ₃ -C ₈ -cycloalkyl selected from the group, each optionally substituted with a halogen,
R ¹ to R ¹¹ , R ^2a , R ^2b , R ^2ab , R 3a , R ^3b , R ^3ab , R ^3c , R ^4a , R ^4b , R ^5a , R ^5b , R ^7a , ^{R 7b ,} R ^8a , and R each group of ^8b is one or more groups selected from the group consisting of halogen, cyano, R', OR', SR', N(R') ₂ , COOR', and CON(R') ₂ ; optionally substituted,
"m" is an integer ranging from 0 to 2]
or its agrochemically acceptable salts, isomers/structural isomers, stereoisomers, diastereoisomers, enantiomers, tautomers, polymorphs, metal complexes or N-oxides thereof.

In another embodiment, the compound of formula (I) is a compound of formula (IA):

Formula (IA)

represented by

In yet another embodiment, the compound of formula (I) is a compound of formula (IB):

Formula (IB)

represented by

In one embodiment, Q is represented by formulas Q1-Q10:

wherein _G1 , _G2 , _G4 , and _G5 independently represent N or ^CR3 , _G3 is ^NR6 , O or S, and Z is O or S, where “n” is an integer ranging from 0-4.

In preferred embodiments, Q is Q1a-Q10b:

wherein # denotes the point of attachment to ring D and R ⁶ is selected from the group consisting of hydrogen, C ₁ -C ₆ -alkyl, and cyclic C _3-10 -alkyl , each R ⁶ group is optionally substituted with one or more halogens, and “n” is an integer ranging from 0-4.

In one embodiment, the invention provides compounds of formula (I) wherein at least one nitrogen is in the fused ring system DE.

In another embodiment, the fused ring system DE is DE-1 through DE-15:

wherein # indicates the point of attachment to ring Q and ● indicates the point of attachment to the group —S(Y) _m R ¹ .

In a preferred embodiment, the present invention provides that Q is Q1a, Q1b, Q1c, Q1h, Q2b, Q3a, Q5b, Q5d, Q6aQ6b, Q9a, Q9b, Q7a, or Q8a;

providing a compound of formula (I) selected from

wherein # indicates the point of attachment to ring D,
R ³ is selected from the group consisting of halogen, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, and S(Y) _0-2R ⁷ ;
R ⁶ is selected from the group consisting of hydrogen, C ₁ -C ₆ -alkyl and C ₃ -C ₁₀ -cycloalkyl;
R ⁷ is C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₆ -haloalkenyl, C ₃ -C ₈ - selected from the group consisting of cycloalkyl,
The fused ring DE is

is selected from the group consisting of

wherein # indicates the point of attachment to ring Q, ● indicates the point of attachment to group —S(Y) _m R ¹ ,
R ² is halogen, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₈ -aryl, C ₇ -C ₉ -aralkyl and C ₃ -C ₆ -heterocyclyl, each aliphatic group optionally substituted with one or more R ^2a groups, and the cyclic groups of R ² being one or more optionally substituted with the R ^2b group of
"m" is an integer ranging from 0 to 2;
"n" is an integer ranging from 0 to 4;
R ¹¹ is halogen, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, OR ⁴ , NR ⁵ R ⁶ , C ₆ -C ₁₀ -aryl, C R ¹¹ is selected from the group consisting of ₇ -C ₁₄ -aralkyl and C ₃ -C ₁₀ -heterocyclyl, each aliphatic group being optionally substituted with one or more R ^11a groups; The cyclic group of may be optionally substituted with one or more R ^11b groups.

In another preferred embodiment, the compound of formula (I) is
2-(1-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(2-(ethylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
6-(1-bromo-2-(ethylsulfonyl)indolizin-3-yl)-7-methyl-3-(trifluoromethyl)-7H-imidazo[4,5-c]pyridazine;
2-(2-(ethylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-5-(trifluoromethyl)benzo[d]oxazole;
2-(2-(ethylsulfonyl)-7-(trifluoromethyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(8-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(1-(3,5-dichlorophenyl)-2-(ethylsulfonyl)-7-(trifluoromethyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4,5-b]pyridine;
2-(6-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5- b] pyridine;
2-(2-(ethylsulfonyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -b] pyridine;
2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5- c] pyridine;
2-(2-(ethylsulfonyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -c] pyridine;
2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)thio)benzo[d]oxazole;
2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)sulfonyl)benzo[d]oxazole;
2-(2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)thio)benzo[d]oxazole;
2-(2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)sulfonyl)benzo[d]oxazole;
2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-c] pyridine;
2-(2-(ethylsulfonyl)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-c]pyridine;
2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
2-(2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
2-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-c]pyridine;
2-(2-(ethylsulfonyl)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-b]pyridine;
2-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(2-(ethylthio)-7-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(2-(ethylthio)-7-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-c]pyridine;
2-(2-(ethylsulfonyl)-7-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-c]pyridine;
2-(2-(ethylthio)-7-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)thio)benzo[d] oxazole;
2-(2-(ethylsulfonyl)-7-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)sulfonyl)benzo[d ] oxazole;
2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)thio)benzo[d]oxazole;
2-(2-(ethylsulfonyl)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)sulfonyl)benzo[d]oxazole;
2-(7-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -c] pyridine;
2-(7-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -b] pyridine;
2-(7-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-c] pyridine;
2-(7-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)thio)benzo[d]oxazole;
2-(7-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(7-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)sulfonyl)benzo[d]oxazole;
2-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-c]pyridine;
2-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)thio)benzo[d]oxazole;
2-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-5-((trifluoromethyl)sulfonyl)benzo[d]oxazole;
2-(2-(ethylthio)-5-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c] pyridine;
2-(2-(ethylthio)-5-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c] pyridine;
2-(2-(ethylsulfonyl)-5-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b ] pyridine;
2-(2-(ethylsulfonyl)-5-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c ] pyridine;
2-(6-chloro-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(2-(ethylthio)-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b] pyridine;
2-(6-chloro-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b] pyridine;
2-(2-(ethylthio)-5-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-c]pyridine;
2-(6-chloro-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine ;
2-(6-chloro-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c] pyridine;
2-(2-(ethylsulfonyl)-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b ] pyridine;
2-(2-(ethylthio)-5-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-c]pyridine;
2-(2-(ethylthio)-5-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(6-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -b] pyridine;
2-(2-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine;
2-(2-(ethylthio)-5-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-c] pyridine;
2-(2-(ethylsulfonyl)-5-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-c]pyridine;
2-(2-(ethylsulfonyl)-5-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-b]pyridine;
2-(6-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(2-(ethylthio)-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c] pyridine;
2-(5-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-b]pyridine;
2-(2-(ethylsulfonyl)-6-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c ] pyridine;
2-(5-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(5-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-c]pyridine;
2-(5-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-c]pyridine;
2-(6-bromo-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(6-bromo-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b] pyridine;
2-(6-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-b]pyridine;
2-(6-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -c] pyridine;
2-(6-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-c] pyridine;
2-(2-(ethylthio)-5-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6- (trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
2-(6-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(2-(ethylthio)-5-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6- (trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-5-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6 -(trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
2-(2-(ethylsulfonyl)-5-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6 -(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(6-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-c]pyridine;
2-(6-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-c]pyridine;
2-(2-(ethylthio)-6-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-6-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine;
2-(5-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -b] pyridine;
2-(5-(4-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -c] pyridine;
2-(2-(ethylthio)-6-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-c]pyridine;
2-(2-(ethylthio)-7-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6- (trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(5-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(5-(4-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-c] pyridine;
2-(2-(ethylsulfonyl)-7-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6 -(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6 -(trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
3-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-7-(trifluoromethyl)-[1,2,4]triazolo [ 4,3-a]pyridine;
2-(2-(ethylthio)-7-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6- (trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
3-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-7-(trifluoromethyl)-[1,2,4]triazolo [4,3-a]pyridine;
2-(2-(ethylthio)-6-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6- (trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-6-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6 -(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(7-(3-chlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 -b] pyridine;
2-(7-(3,5-difluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(7-(3-chlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(2-(ethylsulfonyl)-6-(4-(trifluoromethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-c]pyridine;
2-(7-(3,5-difluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4,5-b]pyridine;
2-(7-(3-chloro-5-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(7-(3-chloro-5-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine;
2-(7-(3,4-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
7-(3,5-dichlorophenyl)-2-(ethylthio)-3-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrazolo[1,5-a ] pyrimidines;
2-(ethylthio)-3-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrazolo[1,5-a]pyrimidine;
7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)-3-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrazolo[1,5- a] pyrimidine;
2-(ethylsulfonyl)-3-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrazolo[1,5-a]pyrimidine;
2-(2-(ethylsulfonyl)-6-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6 -(trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
3-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2,4]triazolo [ 4,3-a]pyridine;
3-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2,4]triazolo [4,3-a]pyridine;
2-(7-(2,3-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-b]pyridine;
2-(2-(ethylthio)-7-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b] pyridine;
2-(7-(2,3-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-phenylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b ] pyridine;
2-(7-(4-chloro-3-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-b]pyridine;
2-(7-(4-chloro-3-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine;
2-(7-(4-chloro-3-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-c]pyridine;
2-(7-(2,4-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-b]pyridine;
2-(7-(2,4-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(7-(2,4-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-c]pyridine;
2-(7-(3-chloro-5-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-c]pyridine;
2-(7-(3-chloro-5-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-c]pyridine;
2-(7-(3,5-bis(trifluoromethyl)phenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl) -3H-imidazo[4,5-b]pyridine;
2-(2-(ethylthio)-7-(3-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(2-(ethylthio)-7-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(7-(3,5-bis(trifluoromethyl)phenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl )-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(3-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-b]pyridine;
2-(2-(ethylthio)-7-methylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylthio)-7-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-c] pyridine;
2-(2-(ethylsulfonyl)-7-methylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(2-(ethylthio)-7-(3-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-c]pyridine;
(7-(3,5-dichlorophenyl)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a] pyrimidin-2-yl)(ethyl)(imino)-6-sulfanone;
2-(2-(ethylsulfonyl)-7-(3-(trifluoromethyl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-c]pyridine;
2-(2-(ethylsulfonyl)-7-(3-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-c]pyridine;
2-(2-(ethylthio)-7-methylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine;
2-(7-(3-chloro-4-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridine;
2-(2-(ethylthio)-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ 4,5-b]pyridine;
2-(2-(ethylsulfonyl)-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4,5-b]pyridine;
2-(ethylthio)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-7 (4H )-on;
2-(7-bromo-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ;
2-(ethylsulfonyl)-N-methyl-3-(7-(trifluoromethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)pyrazolo[1,5-a ] pyrimidin-7-amine;
6-(8-(4-chloro-3-fluorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-7-methyl-3-(trifluoromethyl)-7H-imidazo[4,5- c] pyridazine;
2-(2-(ethylsulfonyl)-7-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3- methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(ethylthio)-N-methyl-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a]pyrimidine -7-amine;
2-(2-(ethylsulfonyl)-7-(3-fluorophenoxy)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4 ,5-b]pyridine;
6-(8-(4-chloro-3-fluorophenyl)-2-(ethylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-7-methyl-3-(trifluoromethyl)-7H - imidazo[4,5-c]pyridazine;
2-(6-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyrazine ;
4-(2-(ethylsulfonyl)-3-(7-methyl-3-(trifluoromethyl)-7H-imidazo[4,5-c]pyridazin-6-yl)indolizin-8-yl)-2 - fluorobenzonitrile;
2-(8-(cyclopropylmethyl)-2-(ethylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine;
2-(7-(4-chloro-1H-pyrazol-1-yl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl )-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(5-methyl-1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl- 6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl )-3H-imidazo[4,5-b]pyridine;
2-(2-(ethylsulfonyl)-7-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3- methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine;
2-(7-cyclopropyl-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[1,5- a] pyrazine;
2-(2-(ethylsulfonyl)-7-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-7- (trifluoromethyl)imidazo[1,2-c]pyrimidine;
4-(2-(ethylsulfonyl)-3-(7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)morpholine;
2-(7-(4-chloro-3-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-7-(trifluoromethyl)-[1,2, 4] triazolo[1,5-c]pyrimidine;
2-(2-(ethylsulfonyl)-7-(1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-7-(trifluoromethyl)- [1,2,4]triazolo[1,5-c]pyrimidine;
2-(2-(ethylsulfonyl)-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4,5-b]pyridine;
6-(1-bromo-2-(ethylsulfonyl)-8-methylindolizin-3-yl)-7-methyl-3-(trifluoromethyl)-7H-imidazo[4,5-c]pyridazine;
6-(8-bromo-2-(ethylsulfonyl)indolizin-3-yl)-3-(difluoromethyl)-7-methyl-7H-imidazo[4,5-c]pyridazine;
2-(2-(ethylsulfonyl)-7-methoxypyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b ] pyridine;
2-(2-(ethylsulfonyl)-7-(methylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5- b] pyridine;
2-(ethylsulfonyl)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-7 ( 4H)-thione;
2-(2-(ethylsulfonyl)-7-(1,1,2,2-tetrafluoroethoxy)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl )-3H-imidazo[4,5-b]pyridine;
2-(7-ethoxy-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyrazine;
Diethyl ((2-(ethylsulfonyl)-3-(6-(trifluoromethyl)imidazo[1,2-a]pyrazin-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl)imino) -16-sulfanone;
2-(ethylsulfonyl)-N,N-dimethyl-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)imidazo[1,2- a] pyridin-8-amine;
6-(2-(ethylsulfonyl)-7-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-7-methyl-3-(trifluoro methyl)-7H-imidazo[4,5-c]pyridazine;
2-(7-(4-chloro-3-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3,5-dimethyl-6-(trifluoromethyl) -3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one;
2-(2-(ethylsulfonyl)-7-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)- 3,5-dimethyl-6-(trifluoromethyl)-3,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one;
2-(7-(3-chloro-5-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2, 4]triazolo[1,5-a]pyrazine;
2-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-7-(trifluoromethyl)imidazo[1,2-c]pyrimidine ;
2-(7-(4-chloro-3-fluorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-methyl-7-(trifluoromethyl)-[ 1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;
2-(7-(5-chloropyridin-2-yl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2, 4]triazolo[1,5-a]pyridine;
2-(2-(ethylsulfonyl)-7-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-6- methyl-7-(trifluoromethyl)-[1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one;
2-(2-(ethylsulfonyl)-7-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)- 7-(trifluoromethyl)-[1,2,4]triazolo[1,5-c]pyrimidine;
Ethyl (3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-2-yl) (methylimino) -16-sulfanone.

Compounds of the invention can exist as one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers, and geometric isomers. One skilled in the art will recognize that one stereoisomer may be more active and/or exhibit beneficial effects when enriched relative to or separated from other stereoisomers. You will understand what you can show. Furthermore, the skilled artisan knows how to separate, enrich, and/or selectively prepare the above stereoisomers. The compounds of the invention may exist as a mixture of stereoisomers, individual stereoisomers or as an optically active form.

When the compound of formula (I) is cationic or capable of forming a cation, the anionic portion of the salt may be inorganic or organic. Alternatively, when the compound of formula (I) is anionic or capable of forming an anion, the cationic portion of the salt may be inorganic or organic. Examples of inorganic anionic moieties of salts include, but are not limited to, chloride, bromide, iodide, fluoride, sulfate, phosphate, nitrate, nitrite, bicarbonate, and bisulphate. . Examples of organic anionic moieties of salts include formate, alkanoate, carbonate, acetate, trifluoroacetate, trichloroacetate, propionate, glycolate, thiocyanate, lactate, succinate. , malate, citrate, benzoate, cinnamate, oxalate, alkyl sulfate, alkyl sulfonate, alkyl sulfonate, aryl disulfonate, alkyl phosphate, aryl phosphate, Including, but not limited to, aryl diphosphates, p-toluenesulfonates, and salicylates. Examples of inorganic cationic moieties of salts include, but are not limited to, alkali metals and alkaline earth metals. Examples of organic cationic moieties of salts include, but are not limited to, pyridine, methylamine, imidazole, benzimidazole, hisidine, phosphazene, tetramethylammonium, tetrabutylammonium, choline, and trimethylamine.

The metal ions in the metal complexes of the compounds of formula (I) are in particular ions of elements of the 2nd main group, especially calcium and magnesium, ions of elements of the 3rd and 4th main groups, especially aluminum, tin and lead. and ions of elements of the 1st to 8th transition groups, especially chromium, manganese, iron, cobalt, nickel, copper and zinc. Particular preference is given to metal ions of elements of the 4th period and the 1st to 8th transition groups. Here, metals can exist in a variety of valences that they can assume.

In one embodiment, the present invention provides compounds of formula (I), agriculturally acceptable salts, metal complexes, structural isomers, stereoisomers, diastereoisomers, enantiomers, chiral isomers, atropisomers thereof. , conformational isomers, rotamers, tautomers, optical isomers, polymorphs, geometric isomers, or N-oxides, and excipients, inert carriers, or surfactants, additives, solid diluents. The composition is provided with other essential ingredients such as agents, liquid diluents, and the like.

Compounds of formula (I) (including all stereoisomers, N-oxides and salts thereof) usually exist in two or more forms and thus formula (I) is represented by formula (I) Includes all crystalline and amorphous forms of the compound. Amorphous forms include embodiments that are solids, such as waxes and gums, and embodiments that are liquids, such as solutions and melts. Crystalline forms include embodiments that represent essentially a single crystalline form, and embodiments that represent mixtures of polymorphs (ie, different crystalline forms). The term "polymorph" refers to a particular crystalline form of a compound that can crystallize in different crystalline forms, which forms have different arrangements and/or conformations of the molecules in the crystal lattice. Polymorphs can have the same chemical composition but can also differ in composition due to the presence or absence of co-crystallized water or other molecules that can be weakly or strongly bound in the lattice. Polymorphs have chemical, physical and They can differ in biological properties. One skilled in the art will appreciate that polymorphs of a compound represented by formula (I) have beneficial effects (e.g., useful suitability for the preparation of formulations, improved biological performance). The preparation and isolation of specific polymorphs of the compounds represented by Formula (I) can be accomplished by methods known to those skilled in the art including, for example, crystallization using selected solvents and temperatures.

In one embodiment, the present invention provides processes for preparing compounds of formula (I) or agriculturally acceptable salts.

Compounds of formula (I) can be prepared according to Schemes 1-23/Examples described herein.

A process for preparing a compound of formula (I), more particularly a compound of formula (Ia) wherein Q is Q1 or Q2 or a compound of formula (Ib), comprises a compound of formula (2) and M is O, S, NR' with a compound of formula (3) or (4) to provide compounds of formula (Ia) and (Ib).

This process is summarized in Scheme 1.

Scheme: 1

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₃ , G ₄ , G ₅ , E, m and n have the meanings given above.

Compounds of formula (3) and formula (4) are either commercially available or are and methods known in WO2015000715 or analogous thereto can be prepared using the methods described in

In Scheme 1, the carboxylic acid groups present in compounds of formula (2) are converted to more reactive functional groups such as acyl halides, mixed anhydrides, acyl azides, N-acylbenzotriazoles, active esters, etc.; by peptide coupling reagents such as bis(2-oxo-3-oxazolidinyl)phosphinic acid chloride (BOP-Cl), dicyclohexylcarbodiimide (DCC), or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) In situ activation followed by formation of an amide bond with a compound of formula (3) in a solvent such as dichloromethane, dichloroethane, N,N-dimethylacetamide, tetrahydrofuran, acetonitrile, or mixtures thereof, yields formula (5). ) can be obtained. Organic non-nucleophilic bases such as triethylamine, ethyldiisopropylamine, pyridine, N-methylpyrrolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene may also be used. The reaction can be carried out at temperatures ranging from about 0.degree. C. to about 150.degree.

a compound of formula (5) in the presence of an acid catalyst such as methanesulfonic acid or paratoluenesulfonic acid in an inert solvent such as N-methylpyrrolidine at a temperature ranging from about 25°C to about 185°C, Compounds of formula (Ia) can be converted by dehydration according to conventional conditions or under microwave conditions. Such processes have been previously described in WO2009131237, WO2010125985, WO2011043404, WO2011040629, WO2012086848, WO2013018928, WO2015000715, and WO2015121136.

Alternatively, compounds of formula (5) can be reacted using diisopropyl azodicarboxylate, triphenylphosphine under Mitsunobu conditions well known to those skilled in the art in an inert solvent such as diethyl ether, tetrahydrofuran and the like from about 25° C. to about At temperatures in the range of 50° C. it can be converted to compounds of formula (Ia) where M is oxygen. This process has been previously described in WO2009131237.

By applying the method of Scheme 1 in the reaction of compounds of formula (2) with compounds of formula (4) compounds of formula (Ib) can be obtained.

A process for the synthesis of compounds of formula (I) represented by compounds of formula (Ic and Id) is shown in Scheme 2. Compounds of formula (Ic) or (Id) are prepared by reacting compounds of formula (6) with compounds of formula (3) or (4) to give compounds of formula (7) or (8) be able to. Additionally, compounds of formulas (7) and (8), wherein X is a halogen, such as fluorine, chlorine, or bromine, are optionally treated with a suitable base, such as an alkali metal carbonate, such as sodium carbonate. or potassium carbonate, or an alkali metal hydride such as sodium hydride, or an alkali metal hydroxide such as sodium hydroxide and potassium hydroxide, in an inert solvent at a temperature in the range of about 25°C to about 110°C. Compounds of formula (Ic) or (Id) can be obtained by reaction with compounds of formula (9) or compounds of formula (10) where M ₁ is eg sodium or potassium at temperature.

Scheme: 2

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₃ , G ₄ , G ₅ , E, m and n have the meanings given above.

Alternatively, the above reaction can also be performed in the presence of a ligand such as xantphos in the presence of a palladium catalyst such as tris(dibenzylideneacetone)dipalladium(0), as described in Tetrahedron, 2005, 61, 5253. It can be carried out in an inert solvent such as toluene or xylene at a temperature in the range of about 100°C to about 150°C. Compounds of formula (I) where Y = O, m = 1 (sulfoxide) and/or m = 2 (sulfone) can be prepared by applying suitable oxidizing agents and conditions well known to those skilled in the art, They can be obtained by oxidation of the corresponding sulfide compounds of formulas (Ic) and (Id). Oxidizing agents such as m-chloroperoxybenzoic acid (mCPBA), hydrogen peroxide/glacial acetic acid, hydrogen peroxide/trifluoroacetic acid, hydrogen peroxide/potassium permanganate, hydrogen peroxide/p-toluenesulfonylimidazole, urea Hydrogen peroxide/trifluoroacetic acid, oxone, sodium periodate, sodium hypochlorite, and other organic peracids and the like can be used for this purpose. Examples of solvents used in this reaction include aliphatic halogenated hydrocarbons such as dichloromethane and chloroform, alcohols such as methanol and ethanol, and mixtures thereof.

Compounds of formula (I) where m = 1 or 2, Y = NR ^Y and/or Y = O are prepared according to Chem. Commun. , 2017, 53, 2064-2067; Tetrahedron Lett. 2005, 46, 8007-8008 and by sulfoximation/sulfilimination of the corresponding sulfide compounds of formulas (Ic) and (Id) using analogous procedures described in WO2015071180A1 can be done.

Compounds of formula (2) are selected from the group consisting of formulas (2a), (2b), and (2c).

wherein R ¹ and R ¹¹ have the same meanings as above.

The syntheses of compounds of formulas (2a), (2b) and (2c) are described in Schemes 3-9.

Scheme: 3

wherein R ¹ , R ¹¹ and n have the meanings given above.

reacting a compound of formula (11) with a compound of formula (12) in a suitable solvent at a temperature in the range of 50-200° C. to obtain a dielectrophilic compound of formula (13); can be done. Examples of solvents include, but are not limited to, N,N-dimethylformamide, dimethylacetamide, 1,4-dioxane, 1,2-dichloromethane, toluene, xylene, and the like.

In step 2, the pyrimidine formation step, the pyrazole derivative compound of formula (14) is converted to the dielectrophilic compound of formula (13) or 1,3 of formula (15) in the presence or absence of a base. -treatment with a diketone compound (e.g., a 1,3-dialdehyde or a 3-(dialkylamino)-prop-2-enal) can undergo a cyclization condensation reaction to give a bicyclic compound of formula (16). can. The preparation of compounds of formula (14) is described in the literature (Acta Chimica Sinica 2003, 63, 855; Organic & Biomolecular Chemistry 2010, 8, 3394). Examples of bases include, but are not limited to piperidine, morpholine, N-methylpiperazine, diethylamine, triethylamine, and the like. Examples of solvents include, but are not limited to, methanol, ethanol, isopropanol, ethylene glycol, and the like. The reaction can be carried out at temperatures ranging from about 50°C to about 150°C.

If one or both of the electrophilic centers present in compounds of formulas (13) and (15) are protected/masked (e.g. the aldehyde is masked as a ketal), condensation in the presence of an acid in a solvent It can be performed. Examples of acids include acetic acid, sulfonic acid (eg PTSA), sulfuric acid, hydrochloric acid that release reactive functional groups. Examples of solvents include, but are not limited to, methanol, ethanol, isopropanol, ethylene glycol, and the like. The reaction can be carried out at temperatures ranging from about 0.degree. C. to about 150.degree. Hydrolysis of compounds of formula (16) can be carried out using bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, bis(tributyltin) oxide in solvents such as tetrahydrofuran, water, methanol, ethanol or mixtures thereof. to give compounds of formula (2a). The reaction can be carried out at temperatures ranging from about 50°C to about 150°C.

Alternatively, compounds of formula (2a) can also be prepared by Scheme 4 below.

Scheme: 4

wherein X is halogen and R ¹ and R ¹¹ have the meanings given above.

Compounds of formula (19) can be obtained in the same manner as described in step 1 of scheme 3 starting from compounds of formula (18). Reaction of compounds of formula (18) can be carried out in the same manner as described in Scheme 3, step 2. Additionally, compounds of formula (20) can be obtained if step 2 is performed in the presence of acetic acid without step 3.

The conversion of compounds of formula (20) to compounds of formula (21) can be carried out in a solvent in the presence of a halogenating agent and in the presence or absence of a base. Examples of solvents include, but are not limited to, acetonitrile, chloroform, tetrahydrofuran, 1,4-dioxane, toluene, N,N-dimethylformamide, and the like. Examples of halogenating agents include, but are not limited to, phosphorus oxychloride, thionyl chloride, phosphorus pentachloride, oxalyl chloride, and the like. Examples of bases include, but are not limited to, N,N-dimethylaniline, diisopropylethylamine, N-methylmorpholine, and the like. The reaction can be carried out at temperatures ranging from 50 to 200°C.

Compounds of formula (21) can be conveniently coupled with a boronic acid or boronic ester compound of formula (22) under standard Suzuki cross-coupling conditions to provide compounds of formula (23). The Suzuki cross-coupling reaction can be performed with a palladium-based catalyst including, but not limited to, 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) or tetrakis(triphenylphosphine)palladium(0) with a suitable in solvents such as tetrahydrofuran (THF), N,N'-dimethylformamide (DMF), 1,2-dimethoxyethane, 1,4-dioxane, or tetrahydrofuran (THF)/water, 1,2-dimethoxyethane/water , 1,4-dioxane/water. The reaction is usually carried out in the presence of a base such as potassium carbonate, cesium carbonate, or potassium phosphate. The reaction temperature is preferentially varied from ambient temperature (20° C.) to It can range up to the boiling point. Hydrolysis of compounds of formula (23) can be performed with bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, bis(tributyltin) oxide in solvents such as tetrahydrofuran, water, methanol, ethanol, toluene or mixtures thereof. to give compounds of formula (2a). The reaction can be carried out at temperatures ranging from about 50°C to 150°C.

Compounds of formula (2aa) can be prepared according to Scheme 5 below.

Scheme: 5

wherein R ¹ and R ¹¹ have the meanings given above.

A pyrazole derivative compound of formula (14) undergoes cyclocondensation with a 1,3-dimethyluracil compound of formula (24) or an alkoxyacrylate derivative of formula (25) in the presence of a base to form a pyrimidine- 5-one derivatives can be obtained. Examples of bases include sodium ethoxide, sodium methoxide, potassium tert-butoxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, and the like. Examples of solvents include methanol, ethanol, isopropanol, ethylene glycol, N,N-dimethylacetamide, N,N-dimethylformamide, and the like. The reaction can be carried out at temperatures ranging from about 50°C to about 150°C. Such reactions are well known in the literature and alternative reactions are well described in the literature (eg J. Org. Chem 2007, 72, 1046; WO2018081417). Halogenation of compounds of formula (26) with phosphorus oxychloride or phosphorus oxybromide can give compounds of formula (28), for example as described in WO201108689. Compounds of formula (27) can be conveniently coupled under standard Suzuki cross-coupling conditions to give compounds of formula (28) as described in step 5 of Scheme 4. Subsequent alkaline hydrolysis of compounds of formula (28) as described in step 6 of Scheme 4 can provide compounds of formula (2aa).

A process for synthesizing compounds of formula (2ab) is shown in Scheme 6:

Scheme: 6

wherein R ¹ and R ¹¹ have the meanings given above.

A bisacetal-protected malonaldehyde compound of formula (29) is treated with bromine, iodine, or chlorine, or a halogenating agent such as N-bromosuccinimide, N-iodosuccinimide, or N-chlorosuccinimide, using hydrochloric acid, sulfuric acid, methane. Halogenation in a suitable solvent, such as water, under acidic conditions that may be produced by utilizing an acid independently selected from sulfonic acid, trifluoroacetic acid, tetrafluoroboric acid, or p-toluenesulfonic to give halogenated aldehydes such as chloromalonaldehyde, iodomalonaldehyde, or bromomalonaldehyde of formula (30). After step 2, compounds of formula (30) can be reacted with pyrazole derivatives of formula (14) under suitable condensation conditions to provide compounds of formula (31). Examples of solvents include, but are not limited to, dimethylsulfoxide, N,N-dimethylacetamide, N,N-dimethylformamide, and mixtures thereof. The reaction can be carried out at temperatures ranging from about 50°C to about 150°C. Compounds of formula (31) can be further conveniently coupled under standard Suzuki cross-coupling conditions to give compounds of formula (32) as described in step 5 of scheme 4. Subsequent alkaline hydrolysis of compounds of formula (32) as described in step 6 of Scheme 4 can provide compounds of formula (2ab).

Alternatively, compounds of formula (31) can also be prepared by cyclizing pyrazole derivatives of formula (14) with commercially available 2-halomalonaldehydes of formula (33) under acid catalyzed conditions. . Examples of acids include, but are not limited to, acetic acid, sulfonic acid (eg PTSA), sulfuric acid, hydrochloric acid. Examples of solvents include, but are not limited to, methanol, ethanol, isopropanol, ethylene glycol, and the like. The reaction can be carried out at temperatures ranging from about 0.degree. C. to about 150.degree. Pyrazolo[1,5-a]pyrimidine derivatives of formula (32) can also be prepared from pyrazole derivatives of formula (14) using either commercially available malonaldehyde (34) or its equivalent (35). It can be prepared after cyclization condensation. Derivative (35) is described in J. Am. Het. Chem. 1974, 44, 51.

A process for synthesizing compounds of formula (2b) is shown in Scheme 7:

Scheme: 7

wherein R ¹¹ and n have the meanings given above.

Compounds of formula (38) can be prepared from 2-aminopyridine derivatives of formula (36) in a two-step procedure, the first step is the addition of formula (36) in a suitable solvent under basic conditions. ) with a haloacetic acid (37). Examples of suitable bases include, but are not limited to, tertiary amines such as trimethylamine and diisopropylethylamine. Examples of suitable solvents include, but are not limited to water, methanol, ethanol, isopropanol, and mixtures thereof. The reaction can be carried out at temperatures ranging from about 50°C to about 150°C.

Intramolecular cyclization of compounds of formula (38) in the presence of phosphorus oxychloride or phosphorus oxybromide in a suitable solvent such as toluene at elevated temperature provides 2-haloimidazoles of formula (39) [ 1,2-a]pyridine analogues can be obtained. Alkoxycarbonylation of compounds of formula (38) using chlorocarbonate alkyls of formula (40) as one carbon source can be performed using organometallic reagents such as n-butyllithium with tetrahydrofuran, diethyl ether, methyl tert- Performed in an ether solvent such as butyl ether, compounds of formula (41) can be obtained. The reaction can be carried out at temperatures ranging from about -78°C to about 25°C (WO2011163355). Subsequent alkaline hydrolysis of compounds of formula (41) as described in step 6 of Scheme 4 can provide compounds of formula (2b).

A process for synthesizing compounds of formula (2c) is shown in Scheme 8:

Scheme: 8

wherein R ² , R ¹¹ and n have the meanings given above.

Compounds of formula (44) include ethyl acetate, acetone, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, dichloroform, chloroform, N,N-dimethylformamide, toluene, xylene, methanol, ethanol. can be prepared by reacting a substituted pyridine compound of formula (42) with an alkyl 2-haloacetate of formula (43) in an inert solvent including, but not limited to, mixtures thereof. Bases such as trimethylamine, pyridine, N,N-diisopropylethylamine, 2,6-lutidine can be used in the reaction. The reaction can be carried out at a temperature ranging from 0° C. to the reflux temperature, and the reaction time is usually in the range of 30 minutes to 48 hours, depending on the starting material, solvent used, reaction temperature and the like.

Indolizine derivatives of formula (46) can be prepared by reacting a compound of formula (44) with a haloalkenyl tosylate of formula (45). The preparation of compounds of formula (45) is described in the literature (Tetrahedron 2018, 74, 5295; Organic Letters 2010, 12, 5518). Inert solvents include ethyl acetate, acetone, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, dichloroform, chloroform, N,N-dimethylformamide, toluene, xylene, methanol, ethanol, and Mixtures can be used in the reaction. Potassium carbonate, sodium carbonate, cesium carbonate, sodium hydroxide, potassium fluoride, lithium hydroxide, trimethylamine, pyridine, N,N-diisopropylethylamine, 2,6-lutidine can be used as bases for the reaction. The reaction can be carried out at temperatures ranging from 0° C. to reflux temperature. The reaction time is generally 1 hour to 48 hours, and varies depending on the starting material, solvent used, reaction temperature and the like. Such reactions are known in the literature and are fully described, eg, in Tetrahedron 2004, 60, 5487.

Subsequent alkaline hydrolysis of compounds of formula (46) as described in step 6 of Scheme 4 can provide compounds of formula (2c).

A process for synthesizing compounds of formula (2ca) is shown in Scheme 9:

Scheme: 9

wherein R ¹ , R ² , R ¹¹ and n have the meanings given above.

Indolizine derivatives of formula (47) can be prepared following step 2 as described in Scheme 8 by reacting compounds of (44) with haloalkenyl tosylates of formula (45a). Compounds of formula (47) can be reacted with compounds of formula (9) or compounds of formula (10) followed by oxidation to provide compounds of formula (48). Compounds of formula (49) can be prepared from compounds of formula (48) by halogenation with a halogenating agent such as N-bromosuccinimide, N-chlorosuccinimide, N-iodosuccinimide. The reaction can be carried out in an inert solvent selected from dichloromethane, 2-dichloromethane, chloroform, carbon tetrachloride, acetic acid, acetonitrile, methanol, N,N-dimethylformamide, etc., or mixtures thereof. The reaction can be carried out at temperatures ranging from 0° C. to reflux temperature. Reaction times are typically 30 minutes to 48 hours and vary depending on the starting materials, solvent used, and reaction temperature.

Compounds of formula (49) can be conveniently coupled under standard Suzuki cross-coupling conditions to give compounds of formula (50) as depicted in step 5 of Scheme 4. Subsequent alkaline hydrolysis of compounds of formula (50) as described in step 6 of Scheme 4 can provide compounds of formula (2ca).

A sub-group of compounds of formula (I) wherein Q is _Q3 , _G5 is ^CR3 and R=H can be represented by compounds of formula (52), compounds of formula (6b) and It can be prepared by reacting a compound of formula (51) to give a compound of formula (52) wherein _G5 is ^CR3 and ^R3 =H.

Scheme: 10

wherein R ³ , R ⁷ , A, G, G ₁ , G ₂ , G ₄ , G ₅ , E and n have the meanings given above.

Cyclization to give compounds of formula (52) can be accomplished with copper acetate ( II) can be carried out in the presence of a catalytic copper(II) salt such as under an oxygen or air atmosphere. The reaction can be carried out at temperatures ranging from about 100°C to about 180°C. Such reactions have precedents in the literature (see, for example, Adv. Synth. Catalysis, 2013, 355, 1741; J. Org. Chem, 2013, 78, 12494). The synthesis of compounds of formula (51) is described in WO2015000715.

Compounds of formula (52) can be reacted with compounds of formula (9) or compounds of formula (10) to provide compounds of formula (53).

Compounds of formula (53A) are prepared in Chem. Commun. , 2017, 53, 2064-2067; Tetrahedron Lett. 2005, 46, 8007-8008 and WO2015071180A1.

Scheme: 11

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₄ , G ₅ , E, m and n have the meanings given above.

Compounds of formula (54) where m = 1 (sulfoxide) and/or m = 2 (sulfone) can be converted to compounds of formula (53) with application of appropriate oxidizing agents and conditions well known to those skilled in the art. ) can be obtained by oxidizing the corresponding sulfide compounds. m-chloroperbenzoic acid (mCPBA), hydrogen peroxide/glacial acetic acid, hydrogen peroxide/trifluoroacetic acid, hydrogen peroxide/potassium permanganate, hydrogen peroxide/p-toluenesulfonylimidazole, urea hydrogen peroxide/trifluoroacetic acid Oxidizing agents such as fluoroacetic acid, oxone, sodium periodate, sodium hypochlorite, and other organic peracids can be used for oxidation. Examples of solvents used in this reaction include aliphatic halogenated hydrocarbons such as dichloromethane and chloroform, alcohols such as methanol and ethanol, and mixtures thereof.

G ₅ with a halogenating agent such as N-chlorosuccinamide, N-bromolosuccinamide, N-iodolosuccinamide in a polar aprotic solvent such as acetonitrile or N,N-dimethylformamide at ambient temperature. Compounds of formula (54) where =CR ³ and R ³ =H can be halogenated to give compounds of formula (Ic ₁ ).

Scheme: 12

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₄ , G ₅ , E, m and n have the meanings given above.

A compound of formula (Ic ₁ ) is reacted with a compound R ³ —B(OR''') ² (R''''=H or R''''=pinacolate) in the presence of a palladium catalyst to give G Compounds of formula (Ic) where ₅ = CR ³ and R ³ = alkyl, cycloalkyl, aryl, heteroaryl can be obtained. Such Suzuki reactions are well precedented in the literature (see, for example, WO2012133607).

A process for synthesizing compounds of formula (6b) is shown in Scheme 12a:

Scheme: 12a

wherein G, E and A have the meanings given above.

Carboxylic acids of formula (6) are converted to Weinreb amides of formula (55) by reaction with N,O-dimethylhydroxylamine by methods known to those skilled in the art analogously to procedures described in WO201175643 and EP2671582. can do. Subsequent treatment of the Weinreb amide of formula (55) with a Grignard reagent of formula ( ^R _CH MgHal) provides compounds of formula (6b) according to the method described in Tetrahedron Letters 1981, 22, 3815. be able to.

A process for synthesizing compounds of formula (1d) wherein Q is _Q4 , _G5 is nitrogen and _G4 is ^CR3 is shown in Scheme 13, then compounds of formula (1d) can be synthesized by the formula It can be prepared by reacting a compound of (56) with a compound of formula (57) optionally in the presence of a suitable base in an inert solvent. Alternatively, when G ₄ is nitrogen, compounds of formula (Id) are optionally preferred compounds of formula (58) and compounds of formula (59) where X ⁻ is a halide ion or mesityl sulfonate. can be prepared by reacting in an inert solvent in the presence of a suitable base.

Scheme: 13

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₄ , G ₅ , E, m and n have the meanings given above.

The synthesis of compounds of formula (56) is described in document WO2015000715. The synthesis of compounds of formula (57) can be achieved analogously to eg EP1371638. Compounds of formula (58) are described, for example, in J. Am. Heterocyclic Chem. 1975, 12, 107 and Synthesis 1977, 1, 17, reacting a compound of formula (56) with O-mesitylenesulfonylhydroxylamine (MSH) or one of its equivalents as an aminating reagent. can be prepared by N-amination.

A subgroup of compounds of formula (I) wherein Q is _Q5 and _G5 is ^CR3 can be represented by compounds of formula (Ie). Compounds of formula (Ie) can be synthesized by reacting compounds of formula (60) with compounds of formula (6b) in analogy to the preparation of compounds of formula (Ic).

Scheme: 14

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₅ , E, m and n have the meanings given above.

One skilled in the art will appreciate that compounds of formula (If) where Q is _Q6 and _G5 is ^CR3 can be similarly prepared by reacting compounds of formula (61) with compounds of formula (57a) or (6a). You will recognize that it can be prepared in

Scheme: 15

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₅ , E, m and n have the meanings given above.

A sub-group of compounds of formula (I) wherein Q is _Q3 and _G5 is nitrogen can be represented by compounds of formula (Ig), compounds of formula (62) and compounds of formula (59) can be prepared by reacting in an inert solvent, optionally in the presence of a suitable base.

Scheme: 16

wherein R ¹ , R ³ , A, G, G ₁ , G ₂ , G ₅ , E, m and n have the meanings given above.

Compounds of formula (62) are described, for example, in J. Am. Heterocyclic Chem. 1975, 12, 107 and Synthesis 1977, 1, 17, reacting a compound of formula (51) with O-mesitylenesulfonylhydroxylamine (MSH) or one of its equivalents as an aminating reagent. can be prepared by N-amination by A sub-group of compounds of formula (I) wherein Q is _Q5 and _G5 is nitrogen can be represented by compounds of formula (Ih), compounds of formula (63) and compounds of formula (59) can be prepared by reacting in an inert solvent, optionally in the presence of a suitable base.

Compounds of formula (63) can be prepared by N-amination by reacting compounds of formula (60) with O-mesitylenesulfonylhydroxylamine (MSH) as an aminating reagent. This process is described in J.M. Heterocyclic Chem. 1975, 12, 107 and Synthesis 1977, 1, 17. The synthesis of compounds of formula (60) is described in document WO2007113558.

wherein R ³ , G ₁ and G ₂ have the meanings given above.

In a further embodiment, reacting a compound of formula (64) with a compound of formula (65), wherein Q is _Q7 , to give a compound of formula (Ii), wherein _G5 is ^CR3 or N including. Scheme 17 summarizes the process for compounds of formula (Ii).

Scheme: 17

wherein R ¹ , R ³ , G, A, G ₁ , G ₂ , G ₅ , G ₆ , E, m and n have the meanings given above.

Compounds of formula (65) are commercially available or can be prepared by methods known per se in WO2017113558 and WO2011090122 or analogously as described therein.

In Scheme 17, N-substituted amidines of formula (66) can be prepared by reacting compounds of formula (64) with compounds of formula (65) in the presence of a suitable base. Examples of suitable bases are alkali metal hydrides such as sodium hydride, alkali metal salts of hexamethyldisilazane such as sodium hexamethyldisilazane, alcoholates such as potassium or sodium tert-butoxide, or lithium diisopropylamide. be. The reaction is carried out in a solvent, preferably such a solvent which is inert under the usual reaction conditions, for example diethyl ether, tetrahydrofuran, 1,4-dioxane, diisopropyl ether, 1,2-dimethoxyethane, tert-butyl in ether solvents such as methyl ether; nitriles such as acetonitrile or propionitrile; aromatic hydrocarbons such as toluene and xylene; aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidine, or dimethylsulfoxide It can be carried out. The reaction can be carried out at temperatures ranging from about 0.degree. C. to about 150.degree. Such reactions have precedents in the literature (see, for example, J. Am. Chem. Soc. 2009, 131, 15080).

Intramolecular oxidative cyclization of N-substituted amidines of formula (66) in the presence or absence of a suitable base is described in J. Am. Org. Chem 2015, 80, 7219; Org. Chem 2014, 79, 4687 can be performed analogously. Examples of oxidizing agents include sodium hypochlorite, lead(IV) acetate, manganese dioxide, iodine, phenyliodine(III) diacetate (PIDA) and phenyliodine(III) bis(trifluoroacetate) (PIFA). of hypervalent iodine (III) reagents. The reaction is carried out in a solvent, preferably a solvent which is inert under common reaction conditions, for example nitriles such as acetonitrile or propionitrile; aromatic hydrocarbons such as toluene or xylene; N,N-dimethylformamide; aprotic polar solvents such as N-methylpyrrolidone, dimethylsulfoxide, or ethyl acetate; halogenated hydrocarbons such as dichloromethane or dichloroethane; alcoholic solvents such as hexafluoroisopropanol, methanol, ethanol, trifluoroethanol, and isopropanol. be able to. Suitable bases include potassium carbonate, sodium carbonate, and cesium carbonate. The reaction can be carried out at temperatures ranging from about 25°C to about 180°C.

Alternatively, compounds of formula (1i) are described in WO201341472 and J. Am. Am. Chem. Soc. 2009, 131, 15080, in a single step comprising, after step 3, oxidative coupling of a compound of formula (65) with a compound of formula (64) with a transition metal catalyst Can be synthesized. Transition metal catalysts include zinc or copper such as copper(I) bromide, copper(I) chloride, copper(I) iodide, copper(II) acetate, zinc chloride, zinc(II) bromide, zinc iodide, etc. contains salt of Suitable bases include, for example, 1,10-phenanthroline, cesium carbonate, sodium carbonate, potassium carbonate. The reaction can be carried out in a solvent, preferably an aromatic hydrocarbon such as 1,2-dichlorobenzene, toluene, or xylene, which is inert under normal reaction conditions. The reaction can be carried out at temperatures ranging from 50°C to 150°C.

Compounds of formula (64) are selected from the group consisting of formulas (64a), (64b), and (64c).

wherein R ¹¹ and n have the meanings given above.

The synthesis of compounds of formulas (64a), (64b) and (64c) is described in Scheme 18 and Scheme 19.

Scheme: 18

wherein R ¹ , R ¹¹ and m have the meanings given above.

In the pyrimidine formation step, pyrazole derivatives of formula (67) are converted to dielectrophilic compounds of formula (13) or 1,3 -diketone (eg, 1,3-dialdehyde or 3-(dialkylamino)-prop-2-enal) can undergo a cyclization condensation reaction to provide compounds of formula (64a). The preparation of compounds of formula (67) is described in the literature (Journal of Heterocyclic Chemistry 2016, 53, 1231).

Scheme: 19

wherein R ¹¹ and n have the meanings given above.

Compounds of formula (68) can be prepared from compounds of formula (41) using a source of ammonia analogously to the methods described in WO201065760 and WO2016133838. Ammonium hydroxide or methanolic ammonia solutions are usually used as ammonia sources. The synthesis of compounds of formula (41) is described in Scheme 7. The reaction can be carried out at temperatures ranging from about 25° C. to about 100° C. under typical reaction conditions using ethereal solvents such as 1,4-dioxane or tetrahydrofuran or alcoholic solvents such as methanol, ethanol and the like. Compounds of formula (64b) can be obtained by reacting compounds of formula (68) with a dehydrating reagent such as, but not limited to, phosphoryl chloride or trifluoroacetic anhydride, analogously to methods described in WO201065760 and EP2740730. can be prepared by The reaction can be carried out at temperatures ranging from about 25° C. to about 120° C. under typical reaction conditions using ethereal solvents such as 1,4-dioxane or tetrahydrofuran.

Compounds of formula (64c) can be prepared starting from compounds of formula (46) following similar reaction sequences and conditions as described for the preparation of compounds of formula (64b) as described in Scheme 19. A general synthesis of compounds of formula (46) is described in Scheme 8.

In one embodiment, Q is Q ₈ and a compound of formula (2) or formula (59) or formula (69) is reacted with a compound of formula (70) to give G ₄ and G ₅ are N including obtaining a compound of formula (1j). Scheme 20 describes a method for preparing compounds of formula (Ij).

Scheme: 20

wherein R ¹ , R ³ , A, Z, G, G ₁ , G ₂ , E, m and n have the meanings given above.

Haloderivatives of compounds of formula (71) are commercially available or can be prepared by methods known in the literature or by other methods known to those skilled in the art. The reaction of compounds of formula (71) with hydrazine can be carried out using reaction conditions known to those skilled in the art (see, for example, Larock, R.C. "Comprehensive Organic Transformations: A Guide to functional Group Preparations, 2nd Ed.", 1999, Wiley-VCH). The intermediate compound of formula (70) in step 2 can be converted to N-methylmorpholine/isobutylchloroformate, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/hydroxybenzotriazole or "The Practice of Peptide Synthesis, 2nd Ed. ., Spring-Verlag, Bodanszy, Miklos (1993)” can be used to react with acids of compounds of formula (2) using a suitable set of amide coupling reagents such as others described in Intermediate hydrazides of formula (71) can be provided. Additionally, acyl hydrazides of formula (71) can be prepared after reacting compounds of formula (70) with acid chlorides of formula (59) in the presence of a suitable base such as N,N-diisopropylethylamine or triethylamine. can be prepared. Formation of triazolo compounds of formula (Ij) can be carried out using phosphorus oxychloride/phosphorus pentachloride, Lawesson's reagent, acetic acid, or polyphosphoric acid at elevated temperature under conventional procedures or under microwave irradiation. It can be achieved after cyclodehydration of the compound. Alternatively, the transformation can be accomplished by reacting a compound of formula (71) with triphenylphosphine dichloride or P(alkyl) ₃ /carbon tetrachloride in the presence of a base such as triethylamine or N,N-diisopropylethylamine, or by those skilled in the art. can also be achieved according to other methods known to the public. Alternatively, the hydrazone of formula (72) can be obtained after step 4 by reacting a compound of formula (70) with an aldehyde compound of formula (69), or by other methods known to those skilled in the art or in the literature. (eg, Larock, R. C. "Comprehensive Organic Transformations: A Guide to functional Group Preparations, 2nd Ed.", 1999, Wiley-VCH). Furthermore, after step 5, compounds of formula (Ij) can be converted to formula It can also be prepared by oxidative cyclization of the hydrazone of (72).

Compounds of formula (69) are selected from the group consisting of formulas (69a), (69b), and (69c).

wherein R ¹ , R ¹¹ and n have the meanings given above.

Compounds of formula (69a-c) can be prepared according to formula (23) by methods known in the literature (e.g. Larock, R.C. "Comprehensive Organic Transformations: A Guide to functional Group Preparations, 2nd edition", 1999, Wiley-VCH). ), (41), and (46) by partial reduction.

A process for preparing compounds of formula (I) wherein Q is _Q9 is to react a compound of formula (6b) with a compound of formula (73) such that _G3 = ^CR3 and ^R3 = Obtaining a compound of formula (74) which is H. Compounds of formula (1k) can then be obtained from compounds of formula (74) following the general reaction sequence described for the synthesis of compound (1c) in Scheme 1. The synthesis of compounds of formula (73) is described in WO2018206479.

Scheme: 21

wherein R ¹ , R ³ , R ⁶ , A, G, G ₁ , G ₂ , G ₃ , Z, E, m and n have the meanings given above.

A process for preparing compounds of formula (I), wherein Q is _Q10 , comprises reacting a compound of formula (2) with a compound of formula (75) to give a compound of formula ( ⁷⁶ ), wherein _G3 = NR6. including obtaining a compound. Compounds of formula (IL) can then be obtained from compounds of formula (76) following the general reaction sequence described in Scheme 1. The synthesis of compounds of formula (75) is described in WO2017084879.

Scheme: 22

wherein X is halogen and R ¹ , R ³ , R ⁶ , R′, A, Z, G ₁ , G ₃ , E, m and n have the meanings given above.

Processes for preparing compounds of formula (I) represented by compounds of formula (IB) are described in Chem. Commun. , 2017, 53, 2064-2067; Tetrahedron Lett. 2005, 46, 8007-8008 and WO2015071180A1, by sulfirimation/sulfoximation of compounds of formula (IA) where n=0.

Scheme: 23

wherein Q, R ¹ , R ^Y , A, G, E and n have the meanings given above.

In one embodiment, the invention provides compositions for controlling or preventing invertebrate pests. The composition comprises a biologically effective amount of a compound of formula (I) and at least one additional ingredient selected from the group consisting of surfactants and auxiliaries.

In yet another embodiment, the present invention provides the compound of formula (I) or its N-oxides and salts in agrochemical compositions of conventional types, such as solutions, emulsions, suspensions, powders, powders, pastes. , granules, presses, capsules and mixtures thereof. Examples of composition types include suspensions (SC, OD, FS, etc.), emulsifiable concentrates (EC, etc.), emulsion concentrates (EW, EO, ES, ME, etc.), capsules (CS, ZC, etc.), Pastes, troches, wettable powders, powders (e.g. WP, SP, WS, DP, DS), presses (e.g. BR, TB, DT), granules (e.g. WG, SG, GR, FG, GG, MG) , insecticides (eg LN), and gel formulations (eg GF) for the treatment of plant propagation material such as seeds. These and other types of compositions are described in "Catalogue of pesticide formulation types and international coding systems", Technical Monograph No. 2, ^6th Ed. May 2008, Crop Life International.

The compositions are described in Mollet and Grubemann, Formulation technology, Wiley VCH, Weinheim, 2001; or Knowles, New developments in crop protection product formulation, Agrow Reports. by known methods as described by DS243, TandF Informa, London, 2005 prepared.

Examples of suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetting agents, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesives, thickeners. , hygroscopic agents, repellents, attractants, feeding stimulants, compatibilizers, bactericides, antifreeze agents, antifoam agents, colorants, tackifiers, or binders.

Suitable solvents and liquid carriers include water and organic solvents such as medium to high boiling mineral oil fractions such as kerosene, diesel oil; oils of vegetable or animal origin; aliphatic hydrocarbons, cyclic hydrocarbons, and aromatics. alcohols, such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; glycol; DMSO; ketones, such as cyclohexanone; esters, such as lactate, carbonic acid. phosphonates; amines; amides such as N-methylpyrrolidone, fatty acid dimethylamides; and mixtures thereof.

Suitable solid carriers or fillers are mineral earths such as silicates, silica gel, talc, kaolin, limestone, lime, chalk, clay, dolomite, diatomaceous earth, bentonite, calcium sulphate, magnesium sulphate, magnesium oxide; For example, cellulose, starch; fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, urea; products of vegetable origin such as cereal flour, bark meal, wood meal, nut shell meal, and mixtures thereof.

Suitable surfactants are surface-active compounds such as anionic, cationic, nonionic and amphoteric surfactants, block polymers, polyelectrolytes and mixtures thereof. Such surfactants can be used as emulsifiers, dispersants, solubilizers, wetting agents, penetration enhancers, protective colloids, or adjuvants. Examples of surfactants are described in McCutcheon's, Vol. 1: Emulsifiers and Detergents, McCutcheon's Directories, Glen Rock, USA, 2008 (International or North American edition).

Suitable anionic surfactants are alkali, alkaline earth or ammonium salts of sulfonic, sulfuric, phosphoric, carboxylic acids and mixtures thereof. Examples of sulfonates include alkylarylsulfonates, diphenylsulfonates, alpha olefinsulfonates, ligninsulfonates, fatty acid and oil sulfonates, ethoxylated alkylphenol sulfonates, alkoxylated arylphenol sulfonates. sulfonates, sulfonates of condensed naphthalenes, sulfonates of dodecylandtridecylbenzene, sulfonates of naphthalene and alkylnaphthalenes, sulfosuccinates, or sulfosuccinamidates. Examples of sulfates are sulfates of fatty acids and oils, sulfates of ethoxylated alkylphenols, sulfates of alcohols, sulfates of ethoxylated alcohols, or sulfates of fatty acid esters. Examples of phosphates are phosphate esters. Examples of carboxylates are alkyl carboxylates and carboxylated alcohol or alkylphenol ethoxylates.

Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants, and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters, which are alkoxylated with 1 to 50 equivalents. Ethylene oxide and/or propylene oxide may be used for alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamides or fatty acid alkanolamides. Examples of esters are fatty acid esters, glycerol esters or monoglycerides. Examples of sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters, or alkylpolyglucosides. Examples of polymeric surfactants are homopolymers or copolymers of vinylpyrrolidone, vinyl alcohol, or vinyl acetate.

Suitable cationic surfactants are quaternary surfactants, eg quaternary ammonium compounds with one or two hydrophobic groups, or salts of long-chain primary amines. Suitable amphoteric surfactants are alkylbetaines and imidazolines. Suitable block polymers are AB or ABA block polymers containing blocks of polyethylene oxide and polypropylene oxide, or ABC block polymers containing alkanols, polyethylene oxide and polypropylene oxide. . Preferred polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamines or polyethyleneamines.

Suitable adjuvants are compounds that have negligible or even no insecticidal activity per se and that improve the biological performance of Compound I against a target. Examples are surfactants, mineral or vegetable oils and other auxiliaries. Further examples are listed in Knowles, Adjuvants and additives, Adgrow Reports DS256, TandF Informa UK, 2006, chapter 5.

Suitable thickeners are polysaccharides (eg, xanthan gum, carboxymethylcellulose), inorganic clays (organically modified or unmodified), polycarboxylates, and silicates. Preferred bactericides are bronopol and isothiazolinone derivatives such as alkylisothiazolinones and benzisothiazolinones. Suitable cryoprotectants are ethylene glycol, propylene glycol, urea, and glycerin. Suitable defoamers are silicones, long-chain alcohols, and salts of fatty acids. Suitable colorants (eg, red, blue, or green) are poorly water-soluble pigments and water-soluble dyes. Examples are inorganic colorants (eg iron oxide, titanium oxide, iron hexacyanoferrate) and organic colorants (eg alizarin, azo and phthalocyanine colorants). Suitable tackifiers or binders are polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylates, biological or synthetic waxes and cellulose ethers.

Examples of types of compositions and their preparation are as follows:

i) water-soluble concentrates (SL, LS)
10-60% by weight of compound I or its N-oxide or salt and 5-15% by weight of wetting agent (e.g. alcohol alkoxylate) up to 100% by weight, water and/or water-soluble solvent (e.g. alcohol ). The active substance dissolves when diluted with water.

ii) dispersible concentrate (DC)

5-25% by weight of Compound I or its N-oxide or salt and 1-10% by weight of a dispersant (eg polyvinylpyrrolidone) are dissolved in an organic solvent (eg cyclohexanone) up to 100% by weight. Dilution with water gives a dispersion.

iii) emulsifiable concentrates (EC)

15-70% by weight of compound I or its N-oxide or salt and 5-10% by weight of an emulsifier (e.g. calcium dodecylbenzenesulfonate and castor oil ethoxylate) in up to 100% by weight of a water-insoluble organic solvent ( aromatic hydrocarbons). Dilution with water gives an emulsion.

iv) emulsions (EW, EO, ES)

5-40% by weight of Compound I or its N-oxide or salt and 1-10% by weight of an emulsifier (e.g. calcium dodecylbenzenesulfonate and castor oil ethoxylate) in 20-40% by weight of a water-insoluble organic solvent (e.g. , aromatic hydrocarbons). This mixture, up to 100% by weight, is introduced into water by emulsifying equipment to form a uniform emulsion. Dilution with water gives an emulsion.

v) Suspension (SC, OD, FS)

In a stirred ball mill, 20-60% by weight of Compound I or its N-oxide or salt, 2-10% by weight of a dispersant and wetting agent (such as sodium lignosulfonate and alcohol ethoxylate), 0.1-2. Grind by addition of wt % thickener (such as xanthan gum) and up to 100 wt % water to produce a fine active suspension. Dilution with water gives a stable suspension of the active substance. For FS type compositions, up to 40% by weight of binder (eg polyvinyl alcohol) is added.

vi) Water-dispersible granules and water-soluble granules (WG, SG)

50-80% by weight of Compound I or its N-oxide or salt is finely ground with the addition of up to 100% by weight of dispersing and wetting agents (e.g. sodium lignosulfonate and alcohol ethoxylates) and is treated with technical equipment (e.g. , extrusion, spray tower, fluidized bed) as water-dispersible or water-soluble granules. Dilution with water gives a stable dispersion or solution of the active substance.

vii) water-dispersible and water-soluble powders (WP, SP, WS)

50-80% by weight of compound I or its N-oxide or salt, 1-5% by weight of a dispersing agent (such as sodium lignosulfonate), 1-3% by weight of a wetting agent (such as alcohol ethoxylate), and up to 100% by weight of solid carrier, eg silica gel, are added and ground in a rotor-stator mill. Dilution with water gives a stable dispersion or solution of the active substance.

viii) Gels (GW, GF)

In a stirred ball mill, 5-25% by weight of Compound I or its N-oxide or salt is combined with 3-10% by weight of a dispersant (e.g. sodium lignosulfonate), 1-5% by weight of a thickener (e.g. carboxymethylcellulose) and up to 100% by weight of water are added and ground to give a fine suspension of the active substance. Dilution with water gives a stable suspension of the active substance.

iv) Microemulsion (ME)

5-20% by weight of compound I or its N-oxide or salt, 5-30% by weight of organic solvent blend (e.g. fatty acid dimethylamide and cyclohexanone), 10-25% by weight of surfactant blend (e.g. alcohol ethoxylates and arylphenol ethoxylates) and up to 100% water. The mixture is stirred for 1 hour to spontaneously form a thermodynamically stable microemulsion.

iv) microcapsules (CS)

5-50% by weight of compound I or its N-oxide or salt, 0-40% by weight of water-insoluble organic solvent (e.g. aromatic hydrocarbon), 2-15% by weight of acrylic monomer (e.g. methyl methacrylate, methacrylic acid, and diol triacrylate) is dispersed in an aqueous solution of a protective colloid (eg polyvinyl alcohol). Poly(methyl acrylate) microcapsules are formed by radical polymerization initiated by a radical initiator. Alternatively, 5-50% by weight of a compound I according to the invention, 0-40% by weight of a water-insoluble organic solvent (eg an aromatic hydrocarbon) and an isocyanate monomer (eg diphenylmethene-4,4′-diisocyanate nanate) is dispersed in an aqueous solution of a protective colloid (eg polyvinyl alcohol). Addition of a polyamine (eg, hexamethylenediamine) forms polyurea microcapsules. The amount of monomer is 1-10% by weight. Weight percentages relate to the total CS composition.

ix) dustable powders (DP, DS)

1-10% by weight of Compound I or its N-oxide or salt is finely ground and intimately mixed with up to 100% by weight of solid carrier, eg finely divided kaolin.

x) Granules (GR, FG)

0.5-30% by weight of Compound I or its N-oxide or salt is finely ground and associated with up to 100% by weight of a solid carrier such as a silicate. Granulation is performed by extrusion, spray drying, or fluid bed.

xi) ultra low volume liquid (UL)

1-50% by weight of Compound I or its N-oxide or salt is dissolved in up to 100% by weight of an organic solvent such as an aromatic hydrocarbon.

Types of compositions i) to xi) optionally contain further auxiliaries, such as 0.1-1% by weight bactericides, 5-15% by weight anti-freezing agents, 0.1- 1% by weight defoamer, and 0.1-1% by weight colorant, and the like.

In another embodiment, the present invention provides an agrochemical composition compound of formula (I), which contains 0.01-95% by weight, preferably 0.1-90%, more preferably 1-70% , in particular from 10 to 60% by weight of active substance. The active substances are used in a purity of 90% to 100%, preferably 95% to 100% (according to NMR spectrum).

Water soluble concentrate (LS), suspoemulsion (SE), flowable concentrate (FS), dry processing powder (DS), slurry processing water dispersible powder (WS), water soluble powder (SS) , Emulsions (ES), Emulsifiable Concentrates (EC) and Gels (GF) are commonly used for the treatment of plant propagation materials, especially seeds. The compositions in question give, after 2- to 10-fold dilution, active substance concentrations of 0.01 to 60% by weight, preferably 0.1 to 40% by weight, in ready-to-use preparations. Application can be done before or during sowing.

Methods for applying or treating Compound I and compositions thereof, respectively, to plant propagation material, particularly seeds, include dressing, coating, pelletizing, dusting, soaking, and in-furrowing the propagation material. ) to apply. Preferably, Compound I, or a composition thereof, respectively, is applied to the plant propagation material by methods such as seed dressing, pelleting, coating, and dusting such that germination is not induced.

When used for plant protection, the amount of active substance applied is 0.001 to 2 kg per hectare, preferably 0.005 to 2 kg per hectare, more preferably 1 kg per hectare, depending on the type of effect desired. 0.05 to 0.9 kg per hectare, in particular 0.1 to 0.75 kg per hectare.

0.1 to 1000 g, preferably 1 to 500 g, more preferably 1 g per 100 kg of plant propagation material (preferably seeds) in the treatment of plant propagation material such as seeds, for example by dusting, coating or soaking the seeds. Amounts of active substance of -100 g, most preferably 5-100 g, are generally required.

When used for the protection of materials or preserved products, the amount of active substance applied will vary depending on the type of application area and the desired effect. Amounts normally applied for the protection of materials are from 0.001 g to 2 kg, preferably from 0.005 g to 1 kg of active substance per cubic meter of treated material.

Various types of oils, wetting agents, adjuvants, fertilizers, or micronutrients, and other control agents (e.g., herbicides, insecticides, fungicides, growth regulators, safeners) may be added to the active substance or It can be added to the composition containing the active substance as a premix or, if appropriate, not until just before use (tank mix). These agents can be mixed with the composition according to the invention in a weight ratio of 1:100 to 100:1, preferably 1:10 to 10:1.

A user can typically apply the compositions according to the present invention from a predosing device, knapsack sprayer, spray tank, spray plane, or irrigation system. Usually the agrochemical composition is made up of water, buffers and/or further auxiliaries up to the desired application concentration, thus obtaining a ready-to-use spray solution or agrochemical composition according to the invention. Usually 20 to 6000 liters, preferably 35 to 1000 liters, more preferably 50 to 500 liters of ready-to-use spray liquid are applied per hectare of agriculturally useful area.

According to one embodiment, the individual components of the composition according to the invention, such as part of a kit or part of a binary or ternary mixture, may be mixed by the user himself in a spray tank, optionally Additional auxiliaries may be added as required.

Accordingly, the compounds and compositions of the present invention are agronomically useful for protecting field crops from herbivorous invertebrate pests, and for protecting other horticultural crops and plants from herbivorous invertebrate pests. It is also useful non-agriculturally. This utility includes crops and other plants (i.e., agronomic and non-agronomic) containing genetic material introduced by genetic engineering (i.e., transgenic) or altered by mutagenesis to provide advantageous traits. agronomic) protection.

The compounds of the invention are characterized by favorable metabolism and/or soil persistence patterns and exhibit activity in controlling a range of agronomic and non-agronomic invertebrate pests. The compounds of the invention, even at low application rates, are active ingredients of preventive and/or curative value in the field of pest control, which are effective against control-resistant pests such as insects and mites. and is well tolerated by warm-blooded species, fish, and plants.

In the context of the present invention, "control of invertebrate pests" means inhibition of invertebrate pest emergence (including mortality) resulting in a significant reduction in feeding or other injury or damage caused by the pest. do. (Relevant expressions are similarly defined.) As referred to in the present invention, the term "invertebrate pest" includes arthropods, gastropods and nematodes of economic importance as pests. The term "arthropods" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs, and centipedes.

The term "gastropod" includes snails, slugs and other stigma. The term "helminth" includes roundworms, heartworms, plant-eating nematodes (Nematoda), trematodes (Tematoda), anatocephalus, tapeworms (Cestoda). All helminths such as Those skilled in the art will recognize that not all compounds are equally effective against all pests.

The compounds of the present invention are economically important agronomic pests in forests, greenhouses, seedlings, ornamental plants, grasses, food and textiles, public and animal health, domestic and commercial structures, domestic and stored products. Active against pests. These include armyworm larvae, armyworms, inchworms, and lepidopteran larvae such as heliothine.

(e.g., fall armyworm (Spodoptera fugiperda JE Smith), beet armyworm (Spodoptera exigua Hubner), black cutworm (Agrotis ipsilon Hufnagel), nettle cabbage looper (Trichoplusia ni Hubner), tobacco budworm (Heliothis virescens Fabricius));

Boring worms, casebearers, webworms and coneworms of the family Oryzidae, aphids and skeletonizers (e.g. European corn borer (Ostrinia nubilalis Hubner), Nabel orangeworm) (navel orangeworm) (Amyelois transitella Walker), corn root webworm (Crambus caliginosellus Clemens), and sod webworm (Herpetogramma licarsisalis Walker) er));

Hamakiga Leafroher, green worms, seedworms (SEED WORM), and fruit worms (FRUIT WORM) (for example, Codlinga) (Cydia Pomonella Linnaeus), Gray GRAPE BERRY MOTH (ENDOPIZA Viteana) Clemens), oriental fruit moth (Grapholita molesta Busck));

as well as many other economically important Lepidoptera such as diamondback moth (Plutella xylostella Linnaeus), pink bollworm (Pectinophora gossypiella Saunders), gypsy moth ( Lymantria dispar Linnaeus));

Cockroach nymphs and adults, including cockroaches of the German cockroach family and cockroach family (for example, oriental cockroach (Blatta orientalis Linnaeus), Asian cockroach (Blatella asahinai Mizukubo), German cockroach (German cockroach) (Blattella gemnanica Linnaeus), brownbanded cockroach (Supella longipalpa Fabricius), American cockroach (Periplaneta americana Linnaeus), brown cockroach (Periplaneta americana Linnaeus) iplaneta brunnea Burmeister), Madeira cockroach (Leucophaea maderae Fabricius) );

Coleoptera leaf feeding larvae and adults, including weevils of the family Pleurotus, Bean Curculion, and Curculionidae (e.g. boll weevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrus oryz Ophilus Kuschel), granary weevil (Sitophilus granarius Linnaeus), rice weevil (Sitophilus oryzae Linnaeus));

Flea beetles of the family Chrysomelidae, cucumber beetles, rootworms, leaf beetles, potato beetles, and worms (e.g. Colorado potato beetle (Leptinotarsa decemlineata Say), western corn rootworm (western c orn rootworm) (Diabrotica virgifera virgifera LeConte));

Scarab beetles and other beetles of the family Chaferidae (e.g. Japanese beetle (Popillia japonica Newman) and European chafer (Rhizotrogus majalis Razoumowsky));

carpet beetle of the family Dermestidae;

Wireworms of the Elateridae family;

bark beetle of the family Scolitidae, and flour beetle of the family Tenebrionidae. Furthermore, this is a scissor -eye adult and larvae (eg, European EARWIG), including the EARWIG, which contains the scissors (EARWIG) of Kuginuki Husamusamisamusae. LINNAEUS), Black IARWIG (BLACK EARWIG) Chelisoches mono Fabricius));

Hemiptera adults and nymphs, e.g. plant bugs of the family Miridae, cicadas of the family Cicadidae, leafhoppers of the family Cicadellidae (e.g. Empoasca spp .), planthoppers of Fulgoroidae and Delphacidae, treehoppers of Membracidae, psyllids of Psyllidae, whiteflies ( Aleyrodidae) whitefly (whitefly), aphid of the family Aphididae, phylloxera of the family Phylloxeridae, mealybug of the family Pseudococcidae, Coccidae e), Marcaidae ( Diaspididae), and scales of the family Margarodidae, and lace bugs of the family Tingidae, stink bugs of the family Stinkbug, stink bugs of the family Lygaeidae (cinch bug) (e.g. Blissus spp.), and other seed bugs, spittlebugs of the family Cercopidae, squash bugs of the family Coreidae, and Pyrrhocoridae red bugs, and cotton stainers. Adults and larvae of the order Arachai, for example spider mites and red mites of the family Tetranychidae (e.g. European red mite (Panychus ulmi Koch), two spotted spider mite (Tetran) ychus urticae Koch), McDaniel mite (Tetranychus mcdanieli McGregor)), flat mites of the family Tenuipalpidae (e.g. citrus flat mite (Brevipalpus lewisi McGregor)), and Corbicula Eriophyidae rust mites and bud mites, as well as other foliar-feeding mites and mites important to human and animal health, i.e., Epidermoptidae dust mites, Demodex mites Follicle mites of the family Demodicidae, grain mites of the family Glycyphagidae, ticks of the order Ixodidae (e.g. deer tick (Ixodes scapularis Say), Australian paralytic ( Australian paralysis tick (Ixodes holocycles Neumann), American dog tick (Dermacentor variabilis Say), lone star tick (Amblyomma americanum Linn) aeus), as well as Psoroptidae, Pyemotidae ), and scab mites and itch mites of the family Sarcoptidae;

Grasshoppers, locusts, and crickets (e.g. migratory grasshoppers (e.g. Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American grasshoppers (e.g. Schistocerc a americana Drury), desert locust ( desert locust (Schistocerca gregaria Forskal), migratory locust (Locusta migratoria Linnaeus), house cricket (Acheta domesticus Linnaeus), cricket Orthoptera adults, including (mole cricket) (Gryllotalpa spp.) and larvae;

Leafminers, midges, fruit flies (Tephritidae), frit flies (e.g. Oscinellafrit Linnaeus), soil maggots, house flies (e.g. Musca domestica Linnaeus), lesser house flies (e.g. Fannia canicularis Linnaeus, F. femoralis Stein), stable flies (e.g. Stomoxys calcitrans Linnaeus ), house fly (face fly), horn fly (horn fly), blow flies (e.g. Chiysomya spp., Phonnia spp.), and other muscoid fly pests, horse flies (e.g. Tabanus spp.), botflies (e.g. Gastrophilus spp., Oestrus spp.), cattle grub (e.g. Hypoderma spp.), deer flies (e.g. Chrysops spp.), keds (e.g. Melophagus ovinus Linnae us), and other Brachycera, mosquitoes (e.g. Aedes spp., Anopheles spp., Culex spp.), blackflies (e.g. Prosimulium spp., Simulium spp.), biting midges, sand flies, Diptera adults and larvae, including sciarids, and other Nematocera;

Adults and larvae of the order Thysanoptera, including the onion thrip (Thrips tabaci Lindeman), and other leaf-feeding thrips;

Ants (e.g. red carpenter ant (Camponotus ferrugineus Fabricius), black carpenter ant (Camponotus pennsylvanicus De Geer), Pharaoh ant (Monomoriumphara onis Linnaeus), little fire ants (Wasmannia auropuncta Roger), fire ants ( fire ant (Solenopsis geminata Fabricius), red imported fire ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), paper ant (crazy ant) t) (Paratrechina longicornis Latreille), pavement ant ) (Tetramorium caespitum Linnaeus), cornfield ant (Lasius alienus Fδrster), odorous house ant (Tapinoma sessile Say)), bee (carpenter bee ), hornet (hornet), hornet ( insect pests of the order Hymenoptera, including yellow jackets, as well as wasps;

Oriental subterranean termite (Reticulitermes flavipes Kollar), Western subterranean termite (Reticulitermes hesperus Banks), Taiwan subterranean termite (Coptotermes formosanus Shira) ki), West Indian drywood termite (Incisitermes immigrans) Snyder), as well as other economically important termite insect pests;

insect pests of the order Thysanura, including, for example, silverfish (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard);

head louse (Pediculus humanus capitis De Geer), body louse (Pediculus humanus humanus Linnaeus), chicken body louse (Menacanthus stramine) us Nitszch), dog biting louse (Trichodectes cams De Geer) , fluff louse (Goniocotes gallinae De Geer), sheep body louse (Bovicola ovis Schrank), short-nosed cattle louse (Haematopinus euryst emus Nitzsch), long-nosed cattle louse (Linognathus vituli Linnaeus) and other sucking and stinging lice that attack humans and animals;

Oriental rat flea (Xenopsylla cheopis Rothschild), cat flea (Ctenocephalides felis Bouche), dog flea (Ctenocephatides canis Curtis), chicken flea (hen flea) (Ceratophyllus gallinae Schrank), chicken Included are insect pests of the order Siphonoptera, including the sticktight flea (Echidnophaga gallinacea Westwood), the human flea (Pulex irritans Linnaeus) and other fleas that attack mammals and birds. Additional arthropod pests encompassed include spiders of the order Araneae, such as the brown recluse spider (Loxosceles reclusa Gertsch and Mulaik), and the black widow spider (Latrodectus mactans Fabricius). ), as well as Centipedes, such as house centipede (Scutigera coleoptrata Linnaeus) are included. Activity includes the orders Nematoda, Taeniida, Trematoda, and Trematoda, including economically important members of the order Cotyridae, Ascaris, Pinworm, Streptoria, Trichinoria, and Enopoules. Members of the class Acrocephalus, such as, but not limited to, economically important agricultural pests (i.e., root knot nematodes of the genus Meloidogyne, spotted lines of the genus Pratylenchus) lesion nematodes, stubby root nematodes of Trichodorus, etc.) and animal and human health pests (i.e. all economically important flukes, tapeworms and roundworms, e.g. , Strongylus vulgaris in horses, Toxocara canis in dogs, Haemonchus contortus in sheep, Diroflaria immitis Leidy in dogs, Anoplocephala peifoli in horses ata) , such as Fasciola hepatica Linnaeus in ruminants).

The compounds of the present invention are the pests of the wings (for example, Alabama Argillacea Hubner (Cotton Leaf Worm), ARCHIPS Argyrospila Walker (Fruit Tree Hamakiga (FRUIT TR) EE LEAF ROLLER), A. Rosana LINNAEUS (European leaf roller), and other Archips spp., Chilo suppressalis Walker (rice stem borer), Cnaphalocrossis medinalis Guenee (rice leaf roller), Crambus ca. liginosellus Clemens (corn root webworm )), Crambus teterrelus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm) ), Earias vittella Fabricius (spotted blueworms ( spotted bollworm), Helicoverpa armigera Hubner (American bollworm), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (Ni Tobacco budworm), Herpetogramma licarsisalis Walker (sodweb sod webworm), Lobesia botrana Denis and Schiffe πnuller (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm, Phylloc nistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus (diamondback moth), Spodoptera exigua Hubner (beet armyworm), Spodoptera litura Fabricius (tobacco cutworm, cluster caterpillar), Spodoptera frugiperda J.C. E. It is particularly active against Smith (fall armyworm), Trichoplusia ni Hubner (cabbage looper) and Tula absoluta Meyrick (tomato leafminer).

The compounds of the present invention also have commercially significant activity against members of the order Homoptera, including: Acyrthisiplionpisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid) , Aphis fabae Scopoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid) ple aphid), Aphis spiraecola Patch ( Spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphonfragaefolii Cockerell (strawberry aphid), Diura phis noxia Kurdjumov/Mordvilko (Russian wheat aphid), Dysaphis plantagina Paaseni (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (mealy plum aphid) hid)), Lipaphis erysimi Kaltenbach (tarnip aphid) , Metopolophium dirrhodum Walker (cereal aphid), Macrosipum euphorbiae Thomas (potato pqtato aphid), Myzus persicae Sulzer (peach potato aphid) each-potato aphid), green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphid and gall aphid), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphumpadi Linnaeus (bird cherry-oat aphid) at aphid)), Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius (English grain aphid), Therioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera aurantii, Boyer de Fonscolombe (comic aphid ( black citrus aphid)), and Toxoptera citiicida Kirkaldy (brown citrus aphid); Adelges spp. (adelgid); Phyloxera devastatrix Pergande (pecan phylloxera); Bemisia tabaci Gennadius (tobacco whitefly, sweetpotato o whitefly)), Bemisia argentifolii Bellows and Perring (silverleaf whitefly ( (silverleaf whitefly)), Dialeurodes citri Ashmead (citrus whitefly) and Trialeurodes vaporariorum Westwood (greenhouse whitefly); ca fabae Harris, (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler (green leafhopper), Nephotettix nigropic us Stal (rice leafhopper), Nilaparvata lugens Stal (brown plant hopper (brown planthopper), Peregrinus maidis Ashmead (corn planthopper), Sogatellafurcifera Horvath (white-backed planthopper), Sogatades ori zicola Muir (rice delphacid, Typhlocyba pomaria McAfee White apple leaf hopper (white apple leafhopper), Erythroneura spp. (grape leafhopper); Magicidada septendecim Linnaeus (periodical cicada); Iceryapurchasi Maskell (cotton cushion scale), Qu adraspidiotus perniciosus Comstock (San Jose scale); Planococcus citri Risso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear psylla, Trioza diospyri Ashmead (persimmon psylla).

These compounds also have activity in members of the order Hemiptera including: Acrostemum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus leucopterus leucopterus. Say (chinch bug), Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus sturellus Her rich-S chaffer (cotton stainer) , Euchistus servus Say (brown stink bug), Euchistus variolrius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (complex of seed bug), Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus linearis Palisot de Beauvois (tarnished plant bug) plant bug)) , Nezara viridula Linnaeus (southern green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus DaEas (large milkweed bug) milkweed bug)), Pseudatomoscelis seriatus Reuter (cotton fleahopper).

Other insects controlled by the compounds of formula (I) of the present invention include: Thrips (e.g. Frankliniella occidentalis Pergande (western flower thrip)), Scirthothnps citri Moulton (Citrus thrips ( citrus thrip), Sericothrips variabilis Beach (soybean thrip), and Thrips tabaci Lindeman (onion thrip); Colorado potato beetle) , Epilachna varivestis Mulsant (Mexican bean beetle) and click beetle larvae of the genera Agliotes, Athous, or Limonius).

In particular, the compounds of formula (I), their N-oxides, their isomers, their polymorphs and their salts are particularly suitable for effectively controlling the following pests:

Insects of the order Lepidoptera (Lepidoptera), such as Agrotis ypsilon, Agrotis segetum, Alabama argillacea, Anticarsia gemmatalis, Argyrestia conjugella, Autographa gamma, Bupalus piniarius, Cacoecia murinana, Capua reticulana, Cheimatobia brumata, Chilo infuscatellus, Coristoneura fumiferana, Coristoneura occidentalis, Cirphis unipuncta, Cydia pomonella, Dendrolimus pini, Diaphania nitidalis, Diatraea grandiosella, Earias insulana, Earias vittella, Elasmopalpus lignosella, Eu poecilia ambiguella, Evetria bouliana, Feltia subterranea, Galleria melloñella, Grapholita funebrana, Grapholita molesta, Helicoverpa armigera, Helicoverpa virescens, Helicoverpa zea , Hella undalis, Hibernia defoliaria, Hyphantria cunea, Hyponomeuta malinellus, Keiferia lycopersicella, Lambdina fiscellaria, Laphygma exigua, Leucop tera coffeella, Leucoptera scitella, Lithocolletis blancardella, Lobesia botrana, Loxostege sticticalis, Leucinodes orbonalis, Lymantria dispar, Lymantria monacha, Lyonetia clerkella, Malacosoma neustria, Mamestra brassicae, Orgyia pseudotsugata, Ostrinia nubilalis, Panolis flammea, Pectinophora gossypiella, Peridroma saucia, Phalera bucephala, Phth orimaea operculella, Phyllocnistis citrella, Pieris brassicae, Plathypena scabra, Plutella xylostella, Pseudoplusia inclusions, Rhyacionia frustrana, Scirpoph aga incertulas, Scrobipalpula absoluta, Sitotroga cerealella, Sparganthis pilleriana, Spodoptera frugiperda, Spodoptera littoralis, Spodoptera litura, Spodoptera exigua, Thaumatopoea pityocampa, Tor trix viridana, Trichoplusia ni and Zeiraphera canadensis; and

Beetles (Coleoptera) such as Agrilus sinuatus, Agriotes lineatus, Agriotes obscurus, Amphimallus solstitialis, Anisandrus dispar, Anthonomus grandis, Anthonomus pomorum, Aphthona euphor idae, Athous haemorrhoidalis, Atomaria linearis, Blastophagus piniperda, Blitophaga undata, Bruchus rufimanus, Bruchus pisorum, Bruchus lentis, Byctiscus betulae, Cassida nebulosa, Cerotoma trifurcata, Cetonia aurata, Ceuthorrhynchus assimilis, Ceuthorrhynchus napi, Chaetocnema tibialis, Conoder us vespertinus, Crioceris asparagi, Ctenicera ssp. , Diabrotica longicornis, Diabrotica semipunctata, Diabrotica undecimpunctata Diabrotica speciosa, Diabrotica virgifera, Epilachna varivestis, Epitrix hir tipennis, Eutinobothrus brasiliensis, Hylobius abietis, Hypera brunneipennis, Hypera postica, Ips typographus, Lema bilineata, Lema melanopus, Leptinotarsa deceml ineta, Limonius californicus, Lissorhoptrus oryzophilus , Melanotus communis, Meligethes aeneus, Melolontha hippocastani, Melontha melolontha, Oulema oryzae, Otiorrhynchus sulcatus, Otiorrhynchus ovatus, Phaedon cochleariae, Ph yllobius pyri, Phyllotreta chrysocephala, Phyllophaga sp. , Phyllopertha horticola, Phyllotreta nemorum, Phyllotreta striolata, Popillia japonica, Sitona lineatus and Sitophilus granaria;

Flies, mosquitoes (Diptera) such as Aedes aegypti, Aedes albopictus, Aedes vexans, Anastrepha ludens, Anopheles maculipennis, Anopheles crucians, Anopheles albimanus, Anopheles gamb iae, Anopheles freeborni, Anopheles leucosphyrus, Anopheles minimus, Anopheles quadrimaculatus, Calliphora vicina, Ceratitis capitata, Chrysomya bezziana, Chrysomya hominivorax, Chrysomya macellaria, Chrysops discalis, Chrysops silacea, Chrysops atlanticus, Cochliomyi a hominivorax, Contarinia sorghicola Cordylobia anthropophaga, Culicoides furens, Culex pipiens, Culex nigripalpus, Culex quinquefasciatus, Culex tarsalis, Culiseta inornata , Culista melanura, Dacus cucurbitae, Dacus oleae, Dasineura brassicae, Delia antique, Delia coarctata, Delia platura, Delia radicum, Dermatobia hominis, Fannia canicularis, Geomyza Tripunctata, Gasterophilus intestinalis, Glossina morsitans, Glossina palpalis, Glossina fuscipes, Glossina tachinoides, Haematobia irritans, Haplodiplosis equestris , Hippelates spp. , Hylemyia platura, Hypoderma lineata, Leptoconops torrens, Liriomyza sativae, Liriomyza trifolii, Lucilia caprina, Lucilia cuprina, Lucilia seriata, Lycori A pectoralis, Mansonia titillanus, Mayetiola destructor, Musca autumnalis, Musca domestica, Muscina stabilans, Oestrus ovis, Opomyza florum, Oscinella frit, Pegomya hysocyami, Phorbia antiqua, Phorbia brassicae, Phorbia coarctta, Phlebototomus argentipes, Psorophora columbiae, Psila rosae, Psorophora disc olor, Prosimulium mixum, Rhagoletis cerasi, Rhagoletis pomonella, Sarcophaga haemorrhoidalis, Sarcophaga spp. , Simulium vittatum, Stomoxys calcitrans, Tabanus bovinus, Tabanus atratus, Tabanus lineola, and Tabanus similis, Tipula oleracea, and Tipula paludosa;

Termites (Isoptera) such as Calotermes flavicollis, Leucotermes flavipes, Heterotermes aureus, Reticulitermes flavipes, Reticulitermes virginicus, Reticulitermes lucifugus, Reticulitermes santonen sis, Reticulitermes grassei, Termes natalensis, and Coptotermes formosanus;

Cockroaches (Diptera), such as Blattella germanica, Blattella asahinae, Periplaneta americana, Periplaneta japonica, Periplaneta brunnea, Periplaneta fuligginosa, Periplaneta austr alasiae, and Blatta orientalis;

Ants, bees, wasps, sawflies (Hymenoptera) such as Athalia rosae, Atta cephalotes, Atta capiguara, Atta cephalotes, Atta laevigata, Atta robusta, Atta sexdens, Att a texana, Crematogaster spp. , Hoplocampa minuta, Hoplocampa testudinea, Lasius niger, Monomorium pharaonis, Solenopsis geminata, Solenopsis invicta, Solenopsis richteri, Solenopsis xyloni, Pogonomyr mex barbatus, Pogonomyrmex californicus, Pheidole megacephala, Dasymutilla occidentalis, Bombus spp. , Vespula squamosa, Paravespula vulgaris, Paravespula pennsylvanica, Paravespula germanica, Dolichovespula maculata, Vespa labro, Polistes rubiginosa, Campono tus floridanus, and Linepithema humile;

Crickets, Grasshoppers, Locusts (Orthoptera) such as Acheta domestica, Gryllotapa gryllotalpa, Locusta migratoria, Melanoplus bivittatus, Melanoplus femurrubrum, Melanoplus mexicanus, Melano opplus sanguinipes, Melanoplus spretus, Nomadcris septemfaciata, Schistocerca americana, Schistocerca gregaria, Dociostaurus maroccanus, Tachycines asynamorus, Oedaleus senegalensis, Zonozerus variegatus, Hieroglyphus daganensis, Kraussaria angulifera, Calliptamus italicus, Chortoicetes terminifera, and Locustana pardalina;
Araneidae, such as Latrodectus mactans, and Loxosceles reclusa;

Fleas (order Fleas) such as Ctenocephalides felis, Ctenocephalides canis, Xenopsylla cheopis, Pulex irritans, Tunga penetrans, and Nosopsyllus fasciatus, silverfish, spotted spots (spots), such as Lepism a saccharina and Thermobia domestica, centipedes (Cipedes), For example, Scutigera oleoptrata, millipedes (millipedes), eg Narceus spp. , earwigs (Earwigs), e.g. forficula auricularia, lice (Pediculus), e.g. Pediculus humanus capitis, Pediculus humanus corporis, Pthirus pubis, Haematopinus eurysternus, Haemato pinus suis, Linognathus vituli, Bovicola bovis, Menopon allinae, Menacanthus stramineus, and Solenopotes capillatus, Collembola (collembola), eg Onychiurus ssp. .

The compounds of formula (I) of the present invention are useful against nematodes: plant parasitic nematodes such as root knot nematode, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne javanica and other Melo idogyne species; Cyst-forming nematodes, Globodera rostochiensis, and other Globodera species; Heterodera avenae, Heterodera glycines, Heterodera schachtii, Heterodera trifolii, and other Heterods era species; Seed gall nematodes, Anguina species; stem and leaf lines Stem and foliar nematode, Aphelenchoides species; Sting nematodes, Belonolaimus longicaudatus and other Belonolaimus species; Pine nematode, Bursaphelenchus xylophilus and other Burs saphelenchus species; Ring nematode, and Criconema species, Criconemella species, Criconemoides species, Mesocriconema species; Stem and bulb nematodes, Ditylenchus destructor, Ditylenchus dipsaci, and other Ditylenchus species; olichodoras species; spiral nematode ( Spiral nematode), Heliocotylenchus multicinctus, and other Helicotylenchus species; Sheath and sheathoid nematode, Hemicycliophora species, and Hemicriconemoides species; niella species; Lance nematode, Hoploaimus species; false rootknot nematode, Nacobbus species; Needle nematode, Longidorus elongatus, and other Longidorus species; Lesion nematode, Pratylenchus neglectus, Pratylenchus pene trans, Pratylenchus curvitatus, Pratylenchus goodeyi, and other Barrowing nematode, Radopholus similis, and other Radopholus species; Reniform nematode, Rotylenchus robustus, and other Rotylenchus species; Scutellonem Species a; Stubby root nematode (Stubby root nematode), Trichodorus primitiveus and other Trichodorus species, Paratrichodorus species; Stunt nematode, Tylenchorhynchus claytoni, Tylenchorhynchus dubius, and other Tylenchorhynchus species; Citrus nematode, Tylenchulus species; Dagger nematode , Xiphinema species; as well as other plant parasitic nematode species.

The compounds of formula (I) and their salts can be used in spiders such as arachnids (of the family Arachnoidea, e.g., Amblyomma americanum, Amblyomma variegatum, Argas persicus, Boophilus annulatus, Boophilus decoratus, Boophilus microplus, Dermacentor silvarum, Hyaloma truncatum, Ixodes ricinus, Ixodes rubicundus, Ornithodorus moubata, Otobius megnini, Derm anyssus gallinae, Psoroptes ovis, Rhipicephalus appendiculatus, Rhipicephalus evertsi, Sarcoptes scabiei, and Eriophyidae spp., such as Aculus schlechtendali, Phyllocoptr ata Tarsonemidae spp., such as Phytonemus pallidus and Polyphagotarsonemus latus; Tenuipalpidae spp., such as Brevipalpus phoenicis; spp., such as Tetranychus cinnabarinus, Tetranychus kanzawai, Tetranychus pacificus, Tetranychus telarius and Tetranychus urticae, Panonychus ulmi, It is also useful for controlling Panonychus citri, as well as oligonychus platensis.

In one embodiment of the invention, the invention is useful for controlling insects selected from sucking or stinging insects, such as insects from the genera Thrips, Diptera, and Hemiptera, especially insects from the following species: provides compounds of formula (I):

Thrips: Frankliniella fusca, Frankliniella occidentalis, Frankliniella tritici, Sirtothrips citri, Thrips oryzae, Thrips palmi, and Thrips tabaci,

Diptera: Aedes aegypti, Aedes albopictus, Aedes vexans, Anastrepha ludens, Anopheles maculipennis, Anopheles crucians, Anopheles albimanus, Anopheles gambiae, Ano Pheles freeborni, Anopheles leucosphyrus, Anopheles minimus, Anopheles quadrimaculatus, Calliphora vicina, Ceratitis capitata, Chrysomya bezziana, Chrysomya hominivorax, Chrysomya macellaria, Chrysops discalis, Chrysops silacea, Chrysops atlanticus, Cochliomyia hominivorax, Contarinia sorghicola Cordylobia anthrop ophaga, Culicoides furens, Culex pipiens, Culex nigripalpus, Culex quinquefasciatus, Culex tarsalis, Culiceta inornata, Culiseta melanura, Dacus cucurbitae, Dacus oleae, Dasin euro brassicae, Delia antique, Delia coarctata, Delia platura, Delia radicum, Dermatobia hominis, Fannia canicularis, Geomyza Tripunctata, Gasterophilus intestinalis, Glossina morsitans, Glossina palpalis, Glossina fuscipes, Glossina tachinoides, Haematobia irritans, Haplodiplosis questris, Hippelates spp. , Hylemyia platura, Hypoderma lineata, Leptoconops torrens, Liriomyza sativae, Liriomyza trifolii, Lucilia caprina, Lucilia cuprina, Lucilia seriata, Lycori A pectoralis, Mansonia titillanus, Mayetiola destructor, Musca autumnalis, Musca domestica, Muscina stabilans, Oestrus ovis, Opomyza florum, Oscinella frit, Pegomya hysocyami, Phorbia antiqua, Phorbia brassicae, Phorbia coarctta, Phlebototomus argentipes, Psorophora columbiae, Psila rosae, Psorophora disc olor, Prosimulium mixum, Rhagoletis cerasi, Rhagoletis pomonella, Sarcophaga haemorrhoidalis, Sarcophaga spp. , Simulium vittatum, Stomoxys calcitrans, Tabanus bovinus, Tabanus atratus, Tabanus lineola, and Tabanus similis, Tipula oleracea, and Tipula paludosa;

Hemiptera, especially aphids: Acyrthosiphon onobrychis, Adelges laricis, Aphidula nasturtii, Aphis fabae, Aphis forbesi, Aphis pomi, Aphis gossypii, Aphis grossulariae, Aphis schneideri, Aphis spiraecola, Aphis sambuci, Acyrthosiphon pisum, Aulacorthum solani, Brachycaudus cardui, Brachycaudus helichrysi, Brachycaudus persicae, Brachycaudus prunicola, Brevicoryne brassicae, Capitophorus horni, Cerosipha gossypii, Chaetosiphon fragaef olii, Cryptomyzus ribis, Dreyfusia nordmannianae, Dreyfusia piceae, Dysaphis radicola, Dysaulacorthum pseudosolani, Dysaphis plantagina, Dysaphis pyri, Empo Asca fabae, Hyalopterus pruni, Hyperomyzus lactucae , Macrosiphum avenae, Macrosiphum euphorbiae, Macrosiphon rosae, Megoura viciae, Melanaphis pyrarius, Metopolophium dirhodum, Myzodes persicae, Myzus ascalonicus, Myzus cerasi, Myzus varians, Nasonovia ribis-nigri, Nilaparvata lugens, Pemphigus bursarius, Perkinsiella saccharicida, Phorodon humuli, Psylla mail , Psylla piri, Rhopalomyzus ascalonicus, Rhopalosiphum maidis, Rhopalosiphum padi, Rhopalosiphum insertum, Sappaphis mala, Sappaphis mali, Schizaphis graminum, Schizoneura lanuginosa, Sitobion avenae, Trialeurodes vaporariorum, Toxoptera aurantiiand, and Viteus vitifolii.

In one embodiment, the present invention provides a biologically effective amount of a compound of formula (I) and a fungicide, insecticide, nematicide, acaricide, biopesticide, herbicide, plant growth regulator, A composition comprising at least one additional biologically active compatible compound selected from antibiotics, fertilizers, and nutrients is provided. Compounds used in compositions and used in combination with compounds of formula (I) are also referred to as active compatible compounds.

Known and reported fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, and nutrients have at least one of formula (I) of the present disclosure. Can be combined with compounds. For example, the fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers, and nutrients disclosed and reported in WO2016156129 and/or WO2017153200 are at least It can be combined with one compound of formula (I) of the present disclosure.

The fungicides, insecticides, nematicides, acaricides, biopesticides, herbicides, plant growth regulators, antibiotics, fertilizers and nutrients reported in WO2016156129 and/or WO2017153200 are at least one of the present disclosure is incorporated herein by reference as a non-limiting example for combination with compounds of formula (I).

In particular, the compounds of the present invention can be used as insecticides, fungicides, nematicides, bactericides, acaricides to form multi-component control agents and provide broader agricultural utility. agents, growth regulators such as rooting stimulants, chemical sterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologically active compounds, or entomopathogenic bacteria, viruses, or fungi. can be mixed with at least one additional biologically active and compatible compound (mixing partner), including but not limited to.

Examples of such biologically active compounds or agents/mixing partners with which the compounds of formula (I) of the present invention can be combined/formulated are disclosed in WO2019072906A1 (pages 27-37). .

In one embodiment, biological agents for admixture with compounds of the present invention include naturally occurring genetically modified viral insecticides, including Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, and members of the Baculoviridae family and insectivorous fungi. drug is included.

In certain instances, combinations with other invertebrate pest control compounds or agents having similar spectrums of control but different mechanisms of action are particularly beneficial in managing resistance. Accordingly, the compositions of the present invention may further comprise a biologically effective amount of at least one additional invertebrate pest control compound or agent having a similar spectrum of control but a different mechanism of action. . Contacting a plant protection compound (e.g., protein) or plant genetically modified to express a plant locus with a biologically effective amount of a compound of the invention also provides broader spectrum plant protection. and are beneficial in managing resistance.

In one embodiment of the invention, the biologically effective amount of the compound of formula (I) in the composition is from 0.1% to 99% by weight relative to the total weight of the composition, preferably range from 5% to 50% by weight relative to the total weight of the

The invention further provides a method of controlling an invertebrate pest, comprising: contacting an area, material, or environment, or said material, plant, seed, soil, surface, or space to be protected from pest attack or infestation, with a biologically effective amount of a compound or composition of the invention; A method is provided, comprising:

Invertebrate pests are controlled, agricultural, horticultural, and/or specialty crop, animal and human health protection is achieved by using an effective amount of one or more of the compounds of the present invention for agricultural and/or non-agricultural use. This is accomplished by direct application to the environment of the pest, including the site of entry, the area to be protected, or the pest to be controlled. Accordingly, the present invention provides a method for the control of foliar and soil-dwelling invertebrates and the protection of agricultural and/or non-agricultural crops, wherein the invertebrates or their environment are treated with a biologically effective amount of or a composition comprising at least one such compound, or at least one such compound and an effective amount of at least one additional biologically active compound, or The method further comprises contacting with a composition comprising the agent. A preferred method of contact is by spraying. Alternatively, a particulate composition containing the compound of the invention can be applied to the leaves of the plant or to the soil. The compounds of the invention can be applied to plants by contacting the plant with a composition comprising the compound of the invention applied as a liquid formulation soil soak, a granular formulation into the soil, a nursery box treatment, or a plant soak. effective in delivery via uptake of Other methods of contact include direct and residual sprays, aerial sprays, seed coatings, microencapsulation, systemic uptake, baits, ear tags, boluses, nebulizers, fumigants, aerosols, dust, and Applications of the compounds or compositions of the invention by many others are included.

The compounds of the invention can be incorporated into bait or within devices such as traps that are consumed by invertebrates. Granules or baits containing 0.01-5% active ingredient, 0.05-10% humectant and 40-99% vegetable flour can be used at very low dosages, especially for direct contact. It is effective in combating soil insects at doses of active ingredient that are lethal by ingestion, without feeding. The compounds of the invention can be applied in their pure state, but in most cases the application will comprise one or more of the compounds together with suitable carriers, diluents and surfactants, optionally Application of the formulation in combination with food according to the intended end use. A preferred method of application involves spraying an aqueous dispersion or refined oil solution of the compound. Combinations with spray oils, spray oil concentrations, spreaders, stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance the efficacy of the compounds.

The amount applied for effective control (i.e., the "biologically effective amount") depends on the species of invertebrate to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or It varies depending on factors such as animals, feeding behavior, mating behavior, ambient moisture and temperature. Under normal circumstances, an application rate of about 0.01 to 2 kg of active ingredient per hectare is sufficient to control pests in agroecosystems, although 0.0001 kg/ha may be sufficient, or 8 kg/ha may be required. For non-agricultural applications, effective usage ranges from about 1.0 to 50 mg/sqm, although 0.1 mg/sqm may be sufficient and 150 mg/sqm may be required. One skilled in the art can readily determine the biologically effective amount necessary for the desired level of invertebrate pest control.

Animal pests, i.e. insects, arachnids and nematodes, plants, the soil or water in which the plants are growing, are treated with a compound of formula (I), its N-oxides and salts by methods of application known in the art. , or a composition containing them. Thus, "contact" includes direct contact (applying the compound/composition directly to the animal pest or plant, typically to the leaves, stems or roots of the plant) and indirect contact ( applying the compound/composition to the locus of animal pests or plants).

The compounds of the present invention, or control compositions comprising the same, can be used to control growing plants and crops against animal pests, particularly animal pests, by contacting the plants/crops with a parasiticidally effective amount of at least one compound of the present invention. , insects, mites, or arachnids to protect against attack or infestation. The term "crop" refers to both growing and harvested crops.

In one embodiment, the present invention provides a method for protecting crops from attack or infestation by invertebrate pests, comprising treating the crops with a biologically effective amount of a compound or composition of the invention, its isomers. , polymorph, N-oxide, or salt.

The compounds of the present invention can be obtained by treating insects or plants, plant propagation material such as seeds, soil, surfaces, materials, or rooms to be protected from insecticidal attack with an insecticidally effective amount of the active compound. It is used as such or in the form of a composition. Application can be both pre- and post-infection by insects of plant propagation material such as plants, seeds, soil, surfaces, materials or rooms.

In one embodiment, the present invention provides a method for the protection of seeds from soil insects and the protection of seedling roots and shoots from soil and foliar insects, comprising pre-sowing and/or pre-germination ) subsequently contacting the seed with a compound or composition of the invention, N-oxide, or salt thereof.

Further, the present invention provides a method for treating or protecting an animal against parasitic infestation or infection comprising a biologically effective amount for the animal of a compound or composition of the present invention, its isomers, Methods are provided comprising administering or applying a polymorph, N-oxide, or veterinarily acceptable salt orally, topically, or parenterally.

When used to treat crop plants, the applied amount (effective dose applied) of the compounds of the invention ranges from 1 gai to 5000 gai per hectare of agricultural or horticultural crops, preferably from 25 g to 600 g per hectare, more preferably 1 gai per hectare. It can range from 50g to 500g per hectare.

The compounds and compositions of the present invention are useful in a variety of cultivated plants such as cereals, root crops, oil crops, vegetables, spices, ornamental plants such as durum and other wheats, barley, oats, rye, maize ( fodder maize and sugar corn/sweet corn and field corn), soybeans, oil crops, oilseed rape, cotton, sunflowers, bananas, rice, rapeseed, turnips, sugar beets, fodder beets, eggplants, Potato, grass, lawn, turf, forage grass, tomato, leek, pumpkin/squash, cabbage, iceberg lettuce, pepper, cucumber, melon, Brassica species , melons, beans, peas, garlic, onions, carrots, tubers such as potatoes, sugarcane, tobacco, grapes, petunias, geraniums/pelargoniums, pansies, and impatiens.

In particular, the compounds or compositions of the present invention may be used in agricultural crops such as cereals, maize, rice, soybeans and other legumes, fruits and fruit trees, grapes, nuts and nut trees, citrus and citrus trees, any horticultural plants, cucurbits, oil-bearing plants, tobacco, coffee, tea, cocoa, sugar beets, sugar cane, cotton, potatoes, tomatoes, onions, peppers, and other vegetables, and ornamental plants. be.

The compounds of the invention are effective both through contact (via soil, glass, walls, bed netting, carpet, plant parts, or animal parts) and ingestion (via food or plant parts).

The compounds of the invention may also be applied against non-crop invertebrate pests such as ants, termites, bees, flies, mosquitoes, crickets, or cockroaches. When used against the above non-crop pests, the compounds of the invention are preferably used in a bait composition.

Baits can be liquid, solid, or semi-solid preparations (eg, gels). Solid baits can be formed into a variety of shapes and forms suitable for each application, eg granules, blocks, sticks, discs. Liquid baits can be filled into a variety of devices to ensure proper application, such as open containers, spray devices, droplet sources, or evaporation sources. open. Gels can be based on aqueous or oily matrices and can be formulated to specific needs in terms of stickiness, moisturizing, or aging properties.

The bait used in the composition is a product sufficiently attractive to stimulate insects such as ants, termites, bees, flies, mosquitoes, crickets or cockroaches to eat it. Attraction can be manipulated using feeding stimulants or sex pheromones. Food stimulants include, but are not limited to, animal and/or vegetable proteins (meat and blood meal, fish blood meal, insect parts, egg yolk), oils and fats of animal and/or plant origin, or, in particular, sucrose, lactose, fructose, dextrose, It is selected from mono-, oligo- or polyorganic sugars derived from glucose, starch, pectin or even molasses or honey. Fresh or decaying parts of fruits, crops, plants, animals, insects, or certain parts thereof can also function as feeding stimulants. Sex pheromones are known to be more insect specific. Certain pheromones have been described in the literature and are known to those skilled in the art.

For use in bait compositions, the typical content of active ingredient is from 0.001% to 15%, desirably from 0.001% to 5% by weight of active compound.

Formulations of the compounds of the invention as aerosols (e.g., in spray cans), oil sprays, or pump sprays are useful for non-professional users to control pests such as flies, fleas, ticks, mosquitoes, or cockroaches. Very suitable. Aerosol recipes preferably include the active compound, solvents such as lower alcohols (eg, methanol, ethanol, propanol, butanol), ketones (eg, acetone, methyl ethyl ketone), paraffin carbonization with a boiling point range of about 50-250°C. Hydrogen (eg kerosene), dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, aromatic hydrocarbons such as toluene, xylene, water, further auxiliaries such as emulsifiers such as sorbitol monooleate, 3-7 mol fatty alcohol ethoxylates, perfume oils such as ether oils, esters of medium-chain fatty acids with lower alcohols, aromatic carbonyl compounds, if appropriate stabilizers such as sodium benzoate, amphoteric interfaces Activator, lower epoxide, triethyl orthoformate, and optionally propellant such as propane, butane, nitrogen, compressed air, dimethyl ether, carbon dioxide, nitrous oxide, or mixtures of these gases.

Oil spray formulations differ from aerosol recipes in that no propellants are used. For use in spray compositions, the content of active ingredient is 0.001-80% by weight, preferably 0.01-50% by weight, most preferably 0.01-15% by weight.

The compounds of the invention and their respective compositions can also be used in mosquito coils and fumigating coils, smoke cartridges, vaporizer plates or long-term vaporizers, moth paper, moth pads. , or in other non-thermal vaporizer systems.

Methods of controlling infections transmitted by insects (e.g. malaria, dengue and yellow fever, lymphatic filariasis, and leishmaniasis) using compounds of formula (I) and their respective compositions also include sheds and Also includes air spraying and impregnation of home surface treatments, curtains, tents, clothing, mosquito nets, tsetse traps, and the like. Insecticide compositions for application to fibres, fabrics, knitted goods, nonwovens, netting materials or foils and tarpaulins are preferably mixtures comprising an insecticide, optionally a repellent and at least one binder. including. Suitable repellents are, for example, N,N-diethyl-meta-toluamide (DEET), N,N-diethylphenylacetamide (DEPA), 1-(3-cyclohexan-1-yl-carbonyl)-2-methylpiperine , (2-hydroxymethylcyclohexyl)acetic acid lactone, 2-ethyl-1,3-hexanediol, indarone, methylneodecanamide (MNDA), pyrethroids not used for insect control, e.g. {(+/-)-3-allyl -2-methyl 4-oxocyclopent-2-(+)-enyl-(+)-trans-chrysanthemate (Esbiothrin), limonene, eugenol, (+)-eucamarol (1), (-) -Potanium extracts such as L -Epi -Eure Camarol or EUCALYPTUS MACULATA, VITEX ROTUNDIFOLIA, CYMBOPOPOGAN MARTINII, CYMBOPOGAN CITRATUS, CYMOPO Derived from a plant -derived plant extract such as GAN NARTDUS (Citronella) or the same as them is a repellent for Suitable binders are, for example, vinyl esters of fatty acids (such as vinyl acetate and vinyl versatate), acrylic acid and methacrylic acid esters of alcohols, such as butyl acrylate, 2-ethylhexyl acrylate, and methyl acrylate, mono- and It is selected from polymers and copolymers of diethylenically unsaturated hydrocarbons, such as styrene, and aliphatic dienes, such as butadiene.

The impregnation of curtains and mosquito nets is generally carried out by soaking the fibrous materials in insecticide emulsions or dispersions or by spraying them onto the nets.

The compounds of the present invention and compositions thereof can be used not only in wooden materials such as trees, fences and sleepers, and buildings such as houses, barns and factories, but also in building materials, furniture, leather, textiles, vinyl products, electric wires and cables. to protect against ants and/or termites, and to control ant and termite damage to crops or humans (e.g., when pests invade homes and public facilities). The compounds of the present invention are not only applied to the surrounding soil surface or subfloor soil to protect wooden materials, but also subfloor concrete surfaces, floor pillars, beams, plywood, timber products such as furniture, particleboards, slabs, etc. It can also be applied to wooden products such as boards, vinyl products such as coated wires and vinyl sheets, and heat insulating materials such as styrene foam.

For applications to crops or to ants that are harmful to humans, the compounds of the invention are applied to the crops or the surrounding soil, or applied directly to the ant colony or the like.

Seed Treatment The present invention further provides, among other things, treated seed comprising a compound of the present invention in an amount ranging from about 0.0001% to about 1% by weight of the seed prior to treatment.

The compounds of the present invention are also used to protect seeds from insect pests, particularly soil-dwelling insect pests and acarid pests, and to protect the resulting plant roots and shoots from soil and foliar insect pests. Suitable for processing.

The compounds of the present invention are particularly useful for the protection of seeds from soil pests and of the resulting plant roots (scarabidae, termites, click beetle larvae) and shoots against soil pests and foliar insects. Protection of the resulting plant roots and shoots is preferred. More preferred is the protection of the resulting plant shoots from sucking insects, most preferred is the protection from aphids, leafhoppers, thrips and whiteflies.

The present invention therefore provides a method for the protection of seeds from insects, especially soil insects, and the protection of seedling roots and shoots from insects, especially soil and foliar insects, comprising pre-sowing and/or pre-emergence A method is provided comprising subsequently contacting the seed with a compound of the invention. Particularly preferred are methods in which plant roots and shoots are protected, more preferably plant shoots are protected from sucking insects, and most preferably plant shoots are protected from aphids. is.

The term seed includes seeds and plant propagules of all kinds including, but not limited to, true seeds, seed parts, suckers, corms, bulbs, fruits, tubers, grains, cuttings, cut shoots, and the like. includes, and in a preferred embodiment means eugenic seed.

The term seed treatment includes all suitable seed treatment techniques known in the art, such as seed dressing, seed coating, seed dusting, seed soaking, seed pelleting.

The invention also includes seeds coated with or containing an active compound. Seeds can be coated with a seed coating composition comprising a compound of the invention. For example, EP3165092, EP3158864, WO2016198644, WO2016039623, WO2015192923, CA2940002, US2006150489, US2004237395, WO2011028115, EP2229808, WO200706 7042, EP1795071, EP1273219, WO200178507, EP1247436, NL1012918 and CA2083415.

The term "coated and/or containing" generally means that the majority of the active ingredient is on the surface of the propagation product upon application, although depending on the method of application a larger portion of the ingredient Or a lesser portion may penetrate the reproductive product. When the propagation product is (re)planted, it can absorb the active ingredient along with the water.

Suitable seeds are those of cereals, root crops, oil crops, vegetables, spices, ornamental plants, such as durum and other wheats, barley, oats, rye, maize (fodder maize and sugar maize/ sweet corn and fodder corn), soybeans, oil crops, oilseed rape, cotton, sunflowers, bananas, rice, rapeseed, turnips, sugar beets, fodder beets, eggplants, potatoes, grasses, lawns, fodder grasses, tomatoes, green onions, pumpkins / pumpkin, cabbage, iceberg lettuce, pepper, cucumber, melon, mustard, melon, bean, pea, garlic, onion, carrot, tubers such as potato, sugar cane, tobacco, grape, petunia, geranium/pelargonium , pansies, and impatiens.

Additionally, the compounds of the invention can be used to treat seed from plants that are resistant to the action of herbicides or fungicides or insecticides for breeding, including genetic engineering methods.

For example, the compounds of the invention can be derived from sulfonylureas, imidazolinones, glufosinate-ammonium or glyphosate-isopropylammonium and similar active substances (see for example EP242236, EP242246) (WO92/00377) (EP257993, US5013659). or have the ability to produce a Bacillus thuringiensis toxin (Bt toxin) that renders the plant resistant to certain pests (EP 142924 , EP 193259), can be used in transgenic crop plants such as cotton.

Furthermore, compounds of the invention are derived from plants with altered characteristics compared to existing plants, which can be produced, for example, by conventional breeding methods and/or the generation of mutants, or by recombinant procedures. can be used to treat seeds of For example, recombinant modification of crop plants (e.g. WO92/11376, WO92/14827, WO91/19806) for the purpose of modifying the starch synthesized in the plant or transgenic crop plants with altered fatty acid composition (WO91 /13972) are described.

Seed treatment application of the compounds of the invention is carried out by spraying or dusting the seeds before sowing the plants and before the plants emerge.

Compositions that are particularly useful for seed treatment include, for example:
A. Soluble concentrates (SL, LS)
B. Emulsion (EW, EO, ES)
C. Suspension (SC, OD, FS)
D. Water-dispersible granules and water-soluble granules (WG, SG)
E. Water-dispersible powders and water-soluble powders (WP, SP, WS)
F. Gel formulation (GF)
G. Dustable powders (DP, DS)

Conventional seed treatment formulations include, for example, Flowable Concentrate FS, Solution LS, Dry Treatment Powder DS, Slurry Treatment Water Dispersible Powder WS, Water Soluble Powder SS, Emulsion Formulation ES and EC, and Gel Formulation GF. . These formulations can be applied to diluted or undiluted seed. Application to the seeds is carried out directly on the seeds prior to sowing or after pregermination of the seeds.

In one embodiment, the FS formulation is used for seed treatment. Typically, FS formulations contain 1-800 g/l active ingredient, 1-200 g/l surfactant, 0-200 g/l cryoprotectant, 0-400 g/l binder, 0-200 g/l /l of pigment and up to 1 liter of solvent, preferably water.

In particular, FS formulations of the compounds of the invention for seed treatment usually contain 0.1-80% by weight (1-800 g/l) active ingredient, 0.1-20% by weight (1-200 g/l) at least one surfactant of, for example, 0.05-5% by weight wetting agent and 0.5-15% by weight dispersing agent, up to 20% by weight, such as 5-20% anti-freezing agent, 0 -15 wt.%, such as 1-15 wt.% pigments and/or dyes; 0-40 wt.%, such as 1-40 wt.% binders (stickers/adhesives); optionally up to 5 wt. %, for example 0.1 to 5% by weight thickener, optionally 0.1 to 2% antifoaming agent, and optionally in an amount, for example 0.01 to 1% by weight Contains preservatives such as biocides, antioxidants, and fillers/vehicles up to 100% by weight.

Seed treatment formulations may further comprise binders and optionally colorants.

Binders can be added to improve the adhesion of the live material to the seeds after treatment. Suitable binders are homopolymers and copolymers derived from alkylene oxides such as ethylene oxide or propylene oxide, polyvinyl acetate, polyvinyl alcohol, polyvinylpyrrolidone and copolymers thereof, ethylene-vinyl acetate copolymers, acrylic homopolymers and copolymers, polyethylene amines, polysaccharides such as polyethyleneamides and polyethylenepyrimidines, cellulose, tylose and starch; polyolefin homopolymers and copolymers such as olefin/maleic anhydride copolymers; polyurethanes, polyesters, polystyrene homopolymers and copolymers.

Optionally, a coloring agent can also be included in the formulation. Colorants or dyes suitable for seed treatment formulations include Rhodamine B, C.I. I. Pigment Red 112, C.I. I. Solvent Red 1, Pigment Blue 15:4, Pigment Blue 15:3, Pigment Blue 15:2, Pigment Blue 15:1, Pigment Blue 80, Pigment Yellow 1, Pigment Yellow 13, Pigment Red 112, Pigment Red 48:2, Pigment Red 48:1, Pigment Red 57:1, Pigment Red 53:1, Pigment Orange 43, Pigment Orange 34, Pigment Orange 5, Pigment Green 36, Pigment Green 7, Pigment White 6, Pigment Brown 25, Basic Violet 10 , Basic Violet 49, Acid Red 51, Acid Red 52, Acid Red 14, Acid Blue 9, Acid Yellow 23, Basic Red 10, and Basic Red 108.

An example of a gelling agent is carrageenan (Satiagel®).

In the treatment of seeds, the application amount of the compounds of the invention is generally between 0.1 g and 10 kg per 100 kg of seed, preferably between 1 g and 5 kg per 100 kg of seed, more preferably between 1 g and 1000 g, especially between 1 g and 200 g per 100 kg of seed. . The present invention therefore also provides seeds comprising a compound of formula (I) or an agriculturally useful salt of I as defined herein. The amount of compound I or an agriculturally useful salt thereof generally varies from 0.1 g to 10 kg per 100 kg of seed, preferably from 1 g to 5 kg per 100 kg of seed, in particular from 1 g to 1000 g per 100 kg of seed. For certain crops such as lettuce, the amount can be higher.

Animal Health The present invention also provides agricultural and/or veterinary compositions comprising at least one compound of the invention.

The present invention provides compounds, N-oxides, or veterinary acceptable salts thereof, or compounds of the present invention in the preparation of medicaments for treating or protecting animals from infestation or infection by invertebrate pests or parasites. It further relates to uses of the composition.

The compounds of formula (I), their N-oxides and/or veterinary acceptable salts are also particularly suitable for use in combating parasites in and on animals.

It is therefore an object of the present invention to provide novel methods for controlling parasites in and on animals. Another object of the present invention is to provide a safer control agent for animals. Another object of the present invention is to provide a control agent for animals that can be used at lower doses than existing control agents. Another object of the present invention is to provide a control agent for animals that provides long-term residual control of parasites.

The present invention also provides a parasiticidally effective amount of at least one compound of formula (I), its N-oxide, or a veterinarily acceptable compound for combating parasites in and on animals. and an acceptable carrier.

The present invention also provides a method for treating, controlling, preventing, and protecting an animal against parasitic infestation and infection, comprising a parasiticidally effective amount of a compound of the present invention, or a composition comprising the same. A method is provided comprising administering or applying the product to an animal orally, topically, or parenterally.

The invention also provides a composition for treating, controlling, preventing, or protecting an animal against parasitic infestation or infection, comprising a parasiticidally effective amount of a compound of the invention, or a composition comprising the same. Provide a process for preparing an object.

The activity of the compounds against agricultural pests requires, for example, low non-emetic doses when administered orally, metabolic compatibility with animals, low toxicity, and endoparasites in and on animals, which require safe handling. and no indication of suitability for the control of ectoparasites.

Surprisingly, it has now been found that the compounds of the invention are suitable for combating endo- and ectoparasites in and on animals.

The compounds of the invention and compositions containing them are preferably used to control and prevent infestations and infections in animals, including warm-blooded animals (including humans) and fish. They are, for example, mammals, such as bovines, sheep, pigs, camels, deer, horses, pigs, poultry, rabbits, goats, dogs and cats, buffaloes, donkeys, fallow deer and reindeer, and fur animals such as Suitable for controlling and preventing infestations and infections in freshwater and saltwater fish such as minks, chinchillas and raccoons, birds such as hens, geese, turkeys and ducks, and fish such as trout, carp and eels is.

The compounds of the invention and compositions containing them are preferably used to control and prevent infestations and infections in domestic animals such as dogs or cats.

Infestations in warm-blooded animals and fish include lice, lice, mites, larvae, larvae, sheep flies, biting flies, muscoid flies, sting flies, flies, myacitic fly larvae, chiggers, beeches, mosquitoes, and fleas. is not limited to

The compounds of the invention and compositions containing them are suitable for the systemic and/or non-systemic control of ectoparasites and/or endoparasites. They may be active against all or some stages of development.

The compounds of the invention are particularly useful for combating ectoparasites.

The compounds of the present invention are particularly useful for combating parasites of the following orders and species, respectively: Fleas (Siphonaptera) such as Ctenocephalides felis, Ctenocephalides cams, Xenopsylla cheopis, Pulex irritans, Tunga penetrans. , and Nosopsylus fasciatus, cockroaches (Blattaria Blattodea) such as Blattella germanica, Blattella asahinae, Periplaneta americana, Periplaneta japonica, Periplaneta brunnea, Periplaneta fuligginosa, Periplaneta australasiae, and Blatta orientalis, flies, mosquitoes (Diptera), For example, Aedes aegypti, Aedes albopictus, Aedes vexans, Anastrepha ludens, Anopheles maculipennis, Anopheles crucians, Anopheles albimanus, Anopheles gambiae, Anophel es freeborni, Anopheles leucosphyrus, Anopheles minimus, Anopheles quadrimaculatus, Calliphora vicina, Chrysomya bezziana, Chrysomya hominivorax, Chrysomya macellaria, Chrysops discalis, Chrysops silacea, Chrysops atlanticus, Cochliomyia hominivorax, Cordylobia anthropophaga, Culicoides furens, Culex pipiens, Culex nigrip quinq uefasciatus, Culex tarsalis, Culista inornata, Culiseta melanura, Dermatobia hominis, Fannia canicularis, Gasterophilus intestinalis, Glossina morsitans, Glossina palpalis, Glossina Fuscipes, Glossina tachinoides, Haematobia irritans, Haplodiplosis equestris, Hippelates spp. , Hypoderma lineata, Leptoconops torrens, Lucilia caprina, Lucilia cuprina, Lucilia sericata, Lycoria pectoralis, Mansonia spp. , Musca domestica, Muscina stabulans, Oestrus ovis, Phlebotomus argentipes, Psorophora columbiae, Psorophora discolor, Prosimulium mixtum, Sarcophaga haemorrho idalis, Sarcophaga spp. , Simulium vittatum, Stomoxys calcitrans, Tabanus bovinus, Tabanus atratus, Tabanus lineola, and Tabanus similis, lice (Phthiraptera) such as Pediculus humanus capitis, Pediculus humanus corporis, Pthirus pubis, Haematopinus eurysternus, Haematopinus suis, Linognathus vituli , Bovicola bovis, Menopon gallinae, Menacanthus stramineus, and Solenopotes capillatus, mites and parasitic mites (Parasitiformes): Ixodida, e.g. Ixodes scapularis, Ixodes holoc yclus, Ixodes pacificus, Rhiphicephalus sanguineus, Dermacentor andersoni , Dermacentor variabilis, Amblyomma americanum, Ambryomma maculatum, Ornithodorus hermsi, Ornithodorus turicata, and parasitic mites (Mesostigmata) such as Orinithonyssus b acoti, and Dermanyssus gallinae, Actinedida (Prostigmata) and Acaridae Suborders (Acaridida (Astigmata)) such as Acarapisa spp. , Cheyletiella spp. , Ornithocheyletia spp. , Myobia spp. , Psorergates spp. , Demodex spp. , Trombicula spp. , Listrophorus spp. , Acarus spp. , Tyrophagus spp. , Caloglyphus spp. , Hypodectes spp. , Pterolichus spp. , Psoroptes spp. , Chorioptes spp. , Otodetects spp. , Sarcptes spp. , Notoedres spp. , Knemidocoptes spp. , Cytodites spp. , and Laminosioptes spp. , Bugs (Heteropterida): Cimex lectularius, Cimex hemipterus, Reduvius senilis, Triatoma spp. , Rhodnius spp. , Panstrongylus spp. , and Arilus critatus, Anoplurida, such as Haematopinus spp. , Linognathus spp. , Pediculus spp. , Phtirus spp. , and Solenopotes spp. , Mallophagida (suborders Arnblycerina, and Ischnocerina), eg, Trimenopon spp. , Menopon spp. , Trinoton spp. , Bovicola spp. , Werneckiella spp. , Lepikentron spp. , Trichodectes spp. , and Felicola spp. .

Roundworm nematodes:

Wipeworm, and Trichinosis (Trichosyringida), eg Trichinellidae (Trichinella spp.), (Trichuridae), Trichuris spp. , Capillaria spp. , Rhabditida, eg Rhabditis spp. , Strongyloides spp. , Helicephalobus spp. , Strongylida, such as Strongylus spp. , Ancylostoma spp. , Necator americanus, Bunostomum spp. (Hookworm), Trichostrongylus spp. , Haemonchus contortus, Ostertagia spp. , Cooperia spp. , Nematodirus spp. , Dictyocaulus spp. , Cyathostoma spp. , Oesophagostomum spp. , Stephanurus dentatus, Ollulanus spp. , Chabertia spp. , Stephanurus dentatus, Syngamus trachea, Ancylostoma spp. , Uncinaria spp. , Globocephalus spp. , Necator spp. , Metastrongylus spp. , Muellerius capillaris, Protostrongylus spp. , Angiostrongylus spp. , Parelaphostrongylus spp. Aleurostrongylus abstrusus, and Dioctophyma renale, Intestinal roundworms (Ascaridida), such as Ascaris lumbricoides, Ascaris suum, Ascaridia galli, Parascaris equiru m, Enterobius vermicularis (Threadworm), Toxocara canis, Toxascaris leonine, Skrjabinema spp. , and Oxyuris equi, Camallanida, such as Dracunculus medinensis (guinea worm) Spirurida, such as Thelazia spp. , Wuchereria spp. , Brugia spp. , Onchocerca spp. , Dirofilari spp. , DiDi petalonema spp. , Setaria spp. , Elaeophora spp. , Spirocerca lupi, and Habronema spp. , Thorny-headed worm (Acanthocephala), eg Acanthocephalus spp. , Macracanthorhynchus hirudinaceus, and Oncicola spp. , Planarian (Plathelminthe): Fluke (Trematoda), eg Faciola spp. , Fascioloides magtna, Paragonimus spp. , Dicrocoelium spp. , Fasciolopsis buski, Clonorchis sinensis, Schistosoma spp. , Trichobilharzia spp. , Alaria a lata, Paragonimus spp. , and Nanocytes spp. , Cercomeromorpha, especially Cestoda (Tapeworms), such as Diphyllobothrium spp. , Tenia spp. , Echinococcus spp. , Dipylidium caninum, Multiceps spp. , Hymenolepis spp. , Mesocestoides spp. , Vampirolepis spp. , Moniezia spp. , Anoplocephala spp. , Sirometra spp. , Anoplocephala spp. , as well as Hymenolepis spp. .

The compounds of formula (I) and compositions containing them are particularly useful for controlling pests from the orders Diptera, Siphonaptera and Ixodida.

In one embodiment, the present invention provides the use of compounds of formula (I) and compositions containing them for combating mosquitoes.

In one embodiment, the present invention provides the use of compounds of formula (I) and compositions containing them for combating flies.

In one embodiment, the present invention provides the use of compounds of formula (I) and compositions containing them for combating fleas.

The use of the compounds of the invention and compositions containing them to combat mites is yet another embodiment of the invention.

The compounds of the present invention are also particularly useful for combating internal parasites (roundworm nematodes, acanthococcus, and planaria).

In one embodiment, administration of the compounds of the invention can be both prophylactic and therapeutic.

In another embodiment, administration of the compounds of the invention is carried out orally, topically/dermally, or parenterally, either directly or in the form of a suitable preparation.

For oral administration to warm-blooded animals, the compounds of the present invention can be formulated into animal feeds, animal feed premixes, animal feed concentrates, pills, solutions, pastes, suspensions, drenches, gels, tablets, boluses, and It can be formulated as a capsule. Additionally, the compounds of the invention may be administered to animals in their drinking water. For oral administration, the dosage form of choice is 0.01 mg/kg to 100 mg/kg animal body weight per day of a compound of the invention, preferably 0.5 mg/kg to 100 mg/kg animal body weight per day. should be provided to

Alternatively, the compounds of the invention can be administered to animals parenterally, for example, by intraruminal, intramuscular, intravenous, or subcutaneous injection. The compounds of the invention can be dispersed or dissolved in a physiologically acceptable carrier for subcutaneous injection. Alternatively, the compounds of the invention may be formulated into an implant for subcutaneous administration. Additionally, the compounds of the invention can be administered to animals transdermally. For parenteral administration, the dosage form chosen should provide the animal with 0.01 mg/kg to 100 mg/kg of animal body weight per day of a compound of the invention.

The compounds of the invention can also be in the form of dips, powders, powders, collars, medals, sprays, shampoos, spot-on and pour-on formulations and ointments or An oil-in-water or water-in-oil emulsion may be applied topically to the animal. For topical application, dips and sprays usually contain from 0.5 ppm to 5,000 ppm, preferably from 1 ppm to 3,000 ppm of the compounds of the invention. Additionally, the compounds of the invention may be formulated as ear tags for animals, particularly quadrupeds such as cows and sheep.

Suitable preparations are solutions such as oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pour-on formulations, gels; emulsions and suspensions for oral or dermal administration. liquids; semi-solid preparations; formulations in which the active compound is processed in an ointment base or an oil-in-water or water-in-oil emulsion base: solid preparations such as powders, premixes or concentrates, granules, pellets , tablets, boluses, capsules; aerosols and inhalants, and shaped articles containing active compounds.

Compositions suitable for injection are prepared by dissolving the active ingredient in a suitable solvent and optionally adding additional ingredients such as acids, bases, buffer salts, preservatives, and solubilizers.

The solution is filtered and filled aseptically.

Suitable solvents are physiologically acceptable solvents such as water, alkanols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycol, N-methylpyrrolidone, 2-pyrrolidone, and mixtures thereof.

The active compounds can optionally be dissolved in physiologically tolerable vegetable or synthetic oils which are suitable for injection.

Suitable solubilizers are solvents which facilitate dissolution of the active compound in the primary solvent or prevent its precipitation. Examples are polyvinylpyrrolidone, polyvinyl alcohol, polyoxyethylated castor oil, and polyoxyethylated sorbitan esters.

Suitable preservatives are benzyl alcohol, trichlorobutanol, p-hydroxybenzoates, and n-butanol.

Oral solutions are administered directly. Concentrates are administered orally after prior dilution to the concentration used. Oral solutions and concentrates are prepared according to the state of the art and as described above for injectable solutions and do not require sterilization procedures.

Solutions for use on the skin are trickled on, spread on, rubbed in, sprinkled on or sprayed on.

Solutions for use on the skin are prepared according to the state of the art and according to those described above for injectable solutions and do not require sterilization procedures.

Further suitable solvents are polypropylene glycol, phenylethanol, phenoxyethanol, esters such as ethyl or butyl acetate, benzyl benzoate, alkylene glycol alkyl ethers, ethers such as dipropylene glycol monomethyl ether, ketones such as acetone, methyl ethyl ketone, Aromatic hydrocarbons, vegetable and synthetic oils, dimethylformamide, dimethylacetamide, transcutol, solketal, propylene carbonate, and mixtures thereof.

It may be advantageous to add thickening agents during preparation. Suitable thickeners are inorganic thickeners such as bentonite, colloidal silicic acid, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohol and its copolymers, acrylates and methacrylates.

Gels are applied or spread on the skin or introduced into body cavities. Gels are prepared by treating a solution prepared as described for the injectable solution with sufficient thickening agent to give a clear material having an ointment-like consistency. The thickeners used are the thickeners mentioned above.

Pour-on formulations are poured or sprayed onto limited areas of the skin and the active compound penetrates the skin and acts systemically. Pour-on formulations are prepared by dissolving, suspending or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures. Other auxiliaries such as colorants, bioabsorption enhancers, antioxidants, light stabilizers, adhesives, etc. are added as needed.

Suitable solvents are, for example, water, alkanols, glycols, polyethylene glycol, polypropylene glycol, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, alkylene glycol alkyl ethers such as ethers, ethers such as dipropylene glycol monomethyl ether, diethylene glycol monobutyl ether, ketones such as acetone, methyl ethyl ketone, cyclic carbonates such as propylene carbonate, ethylene carbonate, aromatic and/or aliphatic hydrocarbons, vegetable oils or synthetic oils, DMF, dimethylacetamide, n-alkylpyrrolidone such as methylpyrrolidone, n-butylpyrrolidone or noctylpyrrolidone, N-methylpyrrolidone, 2-pyrrolidone, 2,2-dimethyl-4-oxy-methylene-1,3-dioxolane, Or glycerol formal.

Suitable coloring agents are, for example, all coloring agents which are acceptable for use on animals and which can be dissolved or suspended.

Suitable absorption-promoting substances are, for example, dimethyl sulfoxide, diffusion oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils and copolymers thereof with polyethers, fatty acid esters, triglycerides or fatty alcohols.

Suitable antioxidants are, for example, sulfites or metabisulfites, such as potassium metabisulfite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole or tocopherol.

A suitable light stabilizer is, for example, novantisolic acid. Suitable adhesives are, for example, cellulose derivatives, starch derivatives, polyacrylates or natural polymers such as alginate, gelatin. Emulsions can be administered orally, dermally or as an injection. Emulsions are either water-in-oil or oil-in-water.

They dissolve the active compound either in the hydrophobic phase or in the hydrophilic phase, contain suitable emulsifiers and, if suitable, other auxiliaries such as colorants, absorption-promoting substances, preservatives, antioxidants. It is prepared by homogenizing it with the solvent of the other phase with the aid of agents, light stabilizers, viscosity-enhancing substances.

Suitable hydrophobic phases (oils) are liquid paraffin, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as di(caprylic/caprylic) glycerides, chain length C ₁ to C ₁₂ triglyceride mixtures with vegetable fatty acids or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids which may also contain hydroxyl groups, mono- and diglycerides of Cs-do fatty acids, fatty acid esters such as , Ethyl Stearate, Di-n-Butyryl Adipate, Hexyl Laurate, Dipropylene Glycol Pelargonate, Esters of Medium Chain Branched Fatty Acids with C ₁₆ -C ₁₈ Saturated Fatty Acid Alcohols, Isopropyl Myristate, Palmitin isopropyl acid, caprylic/capric acid esters of saturated fatty acid esters of chain length C ₁₂ to C ₁₈ , isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid esters, such as synthetic duck tailbone Glandular fat, dibutyl phthalate, diisopropyl adipate and ester mixtures related to the latter, fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol and fatty acids such as oleic acid, and A mixture of them. Suitable hydrophilic phases are water, alcohols such as propylene glycol, glycerol, sorbitol, and mixtures thereof.

Suitable emulsifiers are, for example, nonionic surfactants such as polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethylstearate, alkylphenol polyglycol ethers amphoteric surfactants such as disodium N-lauryl-p-iminodipropionate or lecithin.

Suitable anionic surfactants are, for example, sodium lauryl sulfate, fatty alcohol ether sulfates, mono/dialkyl polyglycol ether orthophosphate monoethanolamine salts. A preferred cationic surfactant is cetyltrimethylammonium chloride.

Suitable further auxiliaries are, for example, viscosity-increasing and emulsion-stabilizing substances, such as carboxymethylcellulose, methylcellulose and other celluloses and starch derivatives, polyacrylates, alginates, gelatine, gum arabic, polyvinylpyrrolidone. , polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycol, waxes, colloidal silicic acid, or mixtures of the above substances.

Suspensions may be administered orally or topically/dermally. They suspend the active compound in the suspending agent, optionally with the addition of other auxiliaries such as wetting agents, colorants, bioabsorption enhancers, preservatives, antioxidants, light stabilizers. prepared by allowing

Liquid suspensions are all homogeneous solvents and solvent mixtures.

Suitable wetting agents (dispersing agents) are the emulsifiers mentioned above.

Other auxiliaries that may be mentioned are those mentioned above.

Semi-solid preparations may be administered orally or topically/dermally. They differ from the suspensions and emulsions described above only in that they are more viscous.

For the production of solid preparations, the active compound is mixed with suitable excipients, if appropriate with the addition of auxiliaries, and brought into the desired form.

All suitable excipients are physiologically acceptable solid inert substances. Those used are inorganic and organic substances. Inorganic substances are, for example, sodium chloride, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxide, titanium oxide, silicic acid, argillaceous earth, precipitated or colloidal silica, or phosphates. Organic substances are, for example, sugar, cellulose, food and feedstuffs, such as milk flour, animal meal, cereal meal and chips, starch, and the like.

Suitable auxiliaries are the preservatives, antioxidants and/or colorants mentioned above.

Other suitable auxiliaries are lubricants and glidants such as magnesium stearate, stearic acid, talc, bentonite, disintegration promoting substances such as starch or crosslinked polyvinylpyrrolidone, binders such as starch, gelatin or Linear polyvinylpyrrolidone, as well as dry binders such as microcrystalline cellulose.

In general, a "parasiticidally effective amount" means an observable effect on growth, including the effect of necrosis, death, retardation, prevention, elimination, destruction, or otherwise reducing the development and activity of the target organism. means the amount of active ingredient required to achieve The parasiticidally effective amount can vary for the various compounds/compositions used in the invention. A parasiticidally effective amount of the composition will also vary depending on prevailing conditions such as desired parasiticidal effect and duration, target species, mode of application, and the like. Compositions that can be used in the invention generally contain from about 0.001 to 95% of a compound of the invention.

In general, it is preferred to apply the compounds of the invention in a total amount of 0.5 mg/kg to 100 mg/kg per day, preferably 1 mg/kg to 50 mg/kg per day. The ready-to-use preparation contains from 10 ppm to 80 weight percent, preferably from 0.1 to 65 weight percent, more preferably from 1 to 50 weight percent of a compound acting against parasites, preferably ectoparasites. %, most preferably at a concentration of 5 to 40 weight percent. The preparations are diluted before use and contain the compounds acting against ectoparasites in concentrations of 0.5 to 90 weight percent, preferably 1 to 50 weight percent. Furthermore, the preparations contain the compounds according to the invention against endoparasites in concentrations of 10 ppm to 2% by weight, preferably 0.05 to 0.9% by weight, very particularly preferably 0.005 to 0.25% by weight. Including in

In one embodiment, a composition comprising a compound of the invention is applied dermally/topically.

In another embodiment, topical application is in the form of compound-containing moldings such as collars, medallions, ear tags, bands for fixing to body parts, and adhesive strips and foils.

Generally, a solid formulation that releases a compound of the invention from 10 mg/kg to 300 mg/kg, preferably from 20 mg/kg to 200 mg/kg, most preferably from 25 mg/kg to 160 mg/kg body weight of the treated animal over the course of three weeks. is preferably applied.

Thermoplastics and soft plastics as well as elastomers and thermoplastic elastomers are used for the preparation of moldings. Suitable plastics and elastomers are polyvinyl resins, polyurethanes, polyacrylates, epoxy resins, celluloses, cellulose derivatives, polyamides and polyesters which are well compatible with the compounds of the invention. A detailed listing of plastics and elastomers, as well as molding preparation procedures, is given in WO2003/086075.

Positive Crop Response:
The compounds of the present invention not only effectively control insect and acarid pests, but also have plant growth-enhancing effects, such as enhanced root growth, drought, high salinity, high temperature, cold, frost, leading to increased yields. or increased resistance to light radiation, improved flowering, increased nutrient utilization (e.g. improved nitrogen assimilation), improved plant products, higher number of effective tillers, increased resistance to fungi, insects, pests, etc. show positive crop reactions such as

Chemistry Examples:

The following examples illustrate, without limiting, methods and processes for preparing the compounds of this invention, including the best mode contemplated by the inventors for carrying out the invention.

Example 1: 2-(1-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 Synthesis of -b]pyridine (Compound No. 1):

a) Step 1: 1-(2-ethoxy-2-oxoethyl)pyridin-1-ium:
To a stirred solution of pyridine (10.2 mL, 126 mmol) in acetonitrile (10 mL) was added ethyl 2-bromoacetate (15.4 mL, 139 mmol) and the reaction mixture was heated to reflux for 18 hours. After completion of the reaction, the reaction mixture was cooled to 25°C. The resulting precipitate was filtered to give 1-(2-ethoxy-2-oxoethyl)pyridin-1-ium (20 g, 120 mmol, 95% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 9.09-9.11 (m, 2H), 8.70-8.74 (m, 1H), 8.25 (dd, J = 7.9, 6 .7 Hz, 2 H), 5.73 (s, 2 H), 4.22 (q, J = 7.1 Hz, 2 H), 1.21 (t, J = 7.1 Hz, 3 H); ESI MS (m/ z) 166.20 (MH) ⁺ .

b) Step 2: Ethyl 2-fluoroindolizine-3-carboxylate:

To a stirred solution of 1-(2-ethoxy-2-oxoethyl)pyridin-1-ium (8 g, 48.1 mmol) in N,N-dimethylformamide (80 mL) was added 2,2-difluorovinyl 4-methylbenzenesulfonate. (7.9 g, 33.7 mmol), potassium carbonate (6.7 g, 48.1 mmol), and triethylamine (6.7 mL, 48.1 mmol) were added. The reaction mixture was heated at 70° C. for 12 hours. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (150 mL) was added to the above reaction mixture and extracted twice with ethyl acetate (300 mL). The combined ethyl acetate layers were washed with brine (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by flash column chromatography on silica gel using ethyl acetate in hexanes as eluent to give ethyl 2-fluoroindolizine-3-carboxylate (4.2 g, 20.3 mmol, yield 42%) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.29 (dq, J = 7.2, 1.0 Hz, 1H), 7.51-7.65 (m, 1H), 7.23-7.27 (m, 1H), 6.72-7.08 (m, 1H), 6.27-6.50 (m, 1H), 4.33 (q, J=7.1Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H); ESI MS (m/z) 208.20 (MH) ⁺ .

c) Step 3: 2-fluoro-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)indolizine-3-carboxamide:

To a stirred solution of potassium tert-butoxide (1.2 g, 10.9 mmol) in N,N-dimethylformamide (5 mL) was added 2-fluoroindolizine-3-carboxylic acid in N,N-dimethylformamide (5 mL). A solution of ethyl (0.9 g, 4.4 mmol) and N-2-methyl-5-(trifluoromethyl)pyridine-2,3-diamine (1 g, 5.2 mmol) was added at 0°C. The reaction mixture was stirred at 25° C. for 2 hours. After completion of the reaction, tetrahydrofuran was removed under reduced pressure to give crude product, which was dissolved in water (25 mL) and extracted with ethyl acetate (75 mL). The ethyl acetate layer was washed with brine (50 mL) and water (50 mL), dried over anhydrous sodium sulfate and concentrated to give crude product. The crude product is purified by column chromatography on silica gel using 40% ethyl acetate in hexanes to give 2-fluoro-N-(2-(methylamino)-5-(trifluoromethyl)pyridine-3 -yl)indolizine-3-carboxamide (550 mg, 1.6 mmol, 36% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 9.38 (dd, J = 7.1, 0.7 Hz, 1 H), 8.75 (d, J = 4.6 Hz, 1 H), 8.30 (t , J = 1.1 Hz, 1H), 7.51-7.72 (m, 2H), 7.17-7.21 (m, 1H), 6.94-7.05 (m, 2H), 6 .55 (s, 1 H), 2.84-2.89 (d, J=4.6 Hz, 3 H); ESI MS (m/z) 352.95 (MH) ⁺ .

d) Step 4: 2-(2-fluoroindolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-fluoro-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)indolizine-3-carboxamide (1.4 g, 4 mmol), p-toluenesulfonic acid monohydrate (2.3 g, 11.9 mmol) was irradiated in a microwave oven at 150° C. for 1 hour under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (100 mL) was added to the above reaction mixture followed by extraction with ethyl acetate (200 mL). The ethyl acetate layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 20% ethyl acetate in hexanes as eluent to give 2-(2-fluoroindolizin-3-yl)-3-methyl-6- (Trifluoromethyl)-3H-imidazo[4,5-b]pyridine (830 mg, 2.5 mmol, 62% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.12 (dd, J = 7.1, 0.7 Hz, 1H), 8.78-8.82 (m, 1H), 8.55 (d, J = 1.5Hz, 1H), 7.65-7.75 (m, 1H), 7.16-7.19 (m, 1H), 6.96 (td, J = 7.0, 1.3Hz, 1H), 6.68 (s, 1H), 3.92 (s, 3H); ESI MS (m/z) 335 (MH) ⁺ .

e) Step 5: 2-(2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-(2-fluoroindolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine ( 830 mg, 2.5 mmol) was added sodium hydride (149 mg, 3.7 mmol) at 0° C. and the reaction mixture was stirred for 30 min. Ethanethiol (0.4 mL, 5 mmol) was added dropwise to the above reaction mixture at 0° C. and the reaction mixture was heated at 60° C. for 1 hour. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (50 mL) was added to the reaction mixture followed by extraction with ethyl acetate (150 mL). The ethyl acetate layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using ethyl acetate in hexanes as eluent to give 2-(2-(ethylthio)indolizin-3-yl)-3-methyl-6- (Trifluoromethyl)-3H-imidazo[4,5-b]pyridine (730 mg, 1.94 mmol, 78% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.83 (q, J = 0.9 Hz, 1H), 8.59-8.60 (m, 1H), 8.43 (dd, J = 7.1 , 0.7 Hz, 1 H), 7.57 (dd, J = 7.8, 1.2 Hz, 1 H), 7.00 (dd, J = 9.0, 6.6, 1.0 Hz, 1 H), 6.81 (s, 1H), 6.72 (td, J=6.9, 1.2Hz, 1H), 3.89 (s, 3H), 2.90-2.96 (q, J=7 .1 Hz, 2 H), 1.19 (t, J=7.3 Hz, 3 H); ESI MS (m/z) 377.05 (MH) ⁺ .

f) Step 6: 2-(2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-(2-(Ethylthio)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (200 mg, 0.5-b) in dichloromethane (3 mL). 5 mmol), m-chloroperbenzoic acid (306 mg, 1.1 mmol) was added portionwise at 0-5°C. The reaction mixture was stirred at 25° C. for 2 hours. After completion of the reaction, the reaction mixture was diluted with aqueous sodium thiosulfate and extracted with dichloromethane (150 mL). The dichloromethane layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(2-(ethylsulfonyl)indolizin-3-yl)-3-methyl -6-(Trifluoromethyl)-3H-imidazo[4,5-b]pyridine (150 mg, 0.4 mmol, 69% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.91 (t, J = 1.0 Hz, 1 H), 8.70 (d, J = 1.5 Hz, 1 H), 8.14 (dd, J = 7 .1, 1.0 Hz, 1H), 7.71-7.91 (m, 1H), 7.11-7.16 (m, 2H), 6.88-6.91 (m, 1H), 3 .7 (s, 3H), 3.39 (q, J = 7.1 hz, 2H), 1.15 (t, J = 7.1 Hz, 3H) ^; .

g) Step 7: 2-(1-bromo-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-(2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (185 mg, 0.45 mmol) in dichloromethane (2 mL) of N-bromosuccinimide (89 mg, 0.5 mmol) was added at 0° C. and the reaction mixture was stirred at 25° C. for 30 min. After completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with dichloromethane (50 mL) three times. The combined dichloromethane layers were washed with brine (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 30% ethyl acetate in hexanes to give 2-(1-bromo-2-(ethylsulfonyl)indolizin-3-yl)-3- Methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (160 mg, 0.3 mmol, 72% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 1.8 Hz, 1 H), 8.69 (d, J = 1.8 Hz, 1 H), 8.11 (d, J = 7 .3Hz, 1H), 7.68 (d, J = 9.2Hz, 1H), 7.24 (dd, J = 9.2, 6.7Hz, 1H), 6.90-6.94 (m, 1H), 3.70 (s, 3H), 3.36-3.46 (m, 2H), 1.12 (t, J=7.3 Hz, 3H); ESI MS (m/z) 486.85 , 489.05 [(MH) ⁺ Br ^79,81 ].

h) Step 8: 2-(1-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b]pyridine:

2-(1-bromo-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl) in a mixture of 1,4-dioxane (2 mL) and water (0.2 mL) )-3H-imidazo[4,5-b]pyridine (110 mg, 0.2 mmol) and (3,5-dichlorophenyl)boronic acid (43.1 mg, 0.2 mmol) was added sodium carbonate (71.8 mg, 0.7 mmol) and tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.01 mmol) were added. The reaction mixture was fully deoxygenated by subjecting it to vacuum/nitrogen cycles three times and heated in a microwave oven at 110° C. for 1.5 hours. After completion of the reaction, the reaction mixture was cooled to 25° C. and filtered through a pad of celite. The filtrate is concentrated under reduced pressure and the crude product is purified by flash column chromatography on silica gel using ethyl acetate in hexane as eluent to give 2-(1-(3,5-dichlorophenyl)-2 -(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (73 mg, 0.1 mmol, 58% yield) rice field. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.92 (t, J = 2.2 Hz, 1 H), 8.71 (t, J = 2.2 Hz, 1 H), 8.15-8.17 (m , 1H), 7.68-7.74 (m, 3H), 7.52-7.55 (m, 1H), 7.16-7.20 (m, 1H), 6.93-6.99 (m, 1H), 3.79 (s, 3H), 3.05 (dtd, J = 63.8, 14.5, 7.3Hz, 2H), 0.89-1.1 (m, 3H) ESI-MS (m/z) 553.90, 554.90 [(MH) ⁺ Cl ^35,37 ].

Example 2: 2-(2-(ethylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b] Synthesis of Pyridine (Compound No. 2):

a) Step 1: 2-(2-iminopyridin-1(2H)-yl)acetic acid:

To a stirred solution of 2-chloroacetic acid (4.0 g, 42.3 mmol) in water (10 mL) was added triethylamine (6.8 mL, 48.7 mmol) dropwise at 25°C. After stirring for 10 minutes, pyridin-2-amine (4.8 g, 50.8 mmol) was added and the resulting brown solution was heated at 90° C. for 5 hours. After cooling to 25° C., ethanol (20 mL) was added and the resulting suspension was stirred at 5° C. for 2 hours. The precipitate was collected by filtration and washed with cold ethanol (30 mL) to give 2-(2-iminopyridin-1(2H)-yl)acetic acid (4.2 g, 28 mmol, 65% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 8.11 (s, 1 H), 7.79-7.91 (m, 2 H), 6.98 (d, J = 7.8 Hz, 1 H), 6. 82 (s, 1H), 4.44 (s, 2H); ESI MS (m/z) 152.95 (MH) ⁺ .

b) Step 2: 2-chloroimidazo[1,2-a]pyridine:

To a stirred solution of 2-(2-iminopyridin-1(2H)-yl)acetic acid (4.2 g, 27.6 mmol) in toluene (50 mL) was added phosphorus oxychloride (7.7 mL, 83 mmol) dropwise, The resulting reaction mixture was heated at 100° C. for 16 hours. After completion of the reaction, the reaction mixture was cooled to 25°C. Cold water (500 mL) was added and the solution was stirred for 15 minutes. The aqueous layer was neutralized with 10% aqueous sodium hydroxide solution and extracted twice with dichloromethane (250 mL). The combined dichloromethane layers were washed with water (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by flash column chromatography on silica gel using ethyl acetate in hexanes as eluent to give 2-chloroimidazo[1,2-a]pyridine (3.2 g, 21 mmol, yield 76 %) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.50 (dt, J = 6.8, 1.2 Hz, 1H), 8.05-8.08 (m, 1H), 7.54 (dq, J = 9.1, 0.9Hz, 1H), 7.33 (ddd, J = 9.2, 6.8, 1.3Hz, 1H), 6.99 (td, J = 6.8, 1.2Hz , 1H); ESI MS (m/z) 152.90 (MH) ⁺ .

c) Step 3: Ethyl 2-chloroimidazo[1,2-a]pyridine-3-carboxylate:

To a stirred solution of 2-chloroimidazo[1,2-a]pyridine (0.5 g, 3.3 mmol) in tetrahydrofuran (10 mL) was added n-butyllithium (1.8 mL, 3.6 mmol) at -78°C. Added dropwise. After stirring for 30 minutes, ethyl chloroformate (0.36 g, 3.3 mmol) in tetrahydrofuran (10 mL) was added to the reaction mixture at the same temperature. The reaction mixture was stirred at -78°C for 1 hour, followed by stirring at 25°C for an additional hour. After completion of the reaction, the reaction was quenched by adding saturated ammonium chloride solution (20 mL) and extracted twice with ethyl acetate (100 mL). The combined ethyl acetate layers were washed with water (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by flash chromatography on silica gel using 30% ethyl acetate in hexanes as eluent to give ethyl 2-chloroimidazo[1,2-a]pyridine-3-carboxylate (0. 5 g, 2.2 mmol, 68% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 9.24 (dt, J = 6.9, 1.2 Hz, 1 H), 7.77 (dt, J = 9.0, 1.2 Hz, 1 H), 7 .66 (ddd, J = 9.0, 6.9, 1.3 Hz, 1 H), 7.31 (td, J = 6.9, 1.3 Hz, 1 H), 4.35 (q, J = 7 .1 Hz, 2 H), 1.45 (t, J = 6.8 Hz, 3 H); ESI MS (m/z) 224.90 (MH) ⁺ .

d) Step 4: 2-chloro-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide:

To a stirred solution of potassium tert-butoxide (0.5 g, 4.5 mmol) in tetrahydrofuran (10 mL) was added ethyl 2-chloroimidazo[1,2-a]pyridine-3-carboxylate (0 .5 g, 2.2 mmol) and N-2-methyl-5-(trifluoromethyl)pyridine-2,3-diamine (0.4 g, 2.2 mmol) were added at 0°C. The reaction mixture was stirred at 25° C. for 1 hour. After completion of the reaction, tetrahydrofuran was removed under reduced pressure to give the crude product, which was dissolved in water (20 mL) and extracted with dichloromethane (75 mL). The dichloromethane layer was washed with brine (50 mL) and water (50 mL), dried over anhydrous sodium sulfate and concentrated to give crude product. The crude product is purified by column chromatography on silica gel using 40% ethyl acetate in hexanes to give 2-chloro-N-(2-(methylamino)-5-(trifluoromethyl)pyridine-3 -yl)imidazo[1,2-a]pyridine-3-carboxamide (0.45 g, 1.2 mmol, 55% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.16-9.22 (m, 2H), 8.34 (q, J = 1.1 Hz, 1H), 7.59-7.76 (m, 3H ), 7.24 (td, J = 7.0, 1.4 Hz, 1 H), 7.03 (q, J = 4.6 Hz, 1 H), 2.90 (d, J = 4.6 Hz, 3 H) ESI MS (m/z) 369.85 (MH) ⁺ .

e) Step 5: 2-(2-chloroimidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-chloro-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3 in N-methyl-2-pyrrolidone (10 mL) A mixture of -carboxamide (0.25 g, 0.68 mmol), p-toluenesulfonic acid monohydrate (0.39 g, 2.03 mmol) was irradiated in a microwave oven at 150° C. for 2 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (50 mL) was added to the above reaction mixture followed by extraction with ethyl acetate (150 mL). The ethyl acetate layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(2-chloroimidazo[1,2-a]pyridin-3-yl) -3-Methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (0.2 g, 0.5 mmol, 76% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.89 (q, J = 0.9 Hz, 1H), 8.68-8.73 (m, 2H), 7.79 (dt, J = 9.0 , 1.1 Hz, 1 H), 7.60 (ddd, J = 9.0, 7.0, 1.3 Hz, 1 H), 7.20 (td, J = 7.0, 1.2 Hz, 1 H), 3.92 (s, 3H); ESI MS (m/z) 352.05 (MH) ⁺ .

f) Step 6: 2-(2-(ethylthio)imidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b] Pyridine:

2-(2-chloroimidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4 in dry N,N-dimethylformamide (5 mL) To a stirred solution of ,5-b]pyridine (0.3 g, 0.9 mmol) was added sodium hydride (0.1 g, 1.7 mmol) at 0° C. and the reaction mixture was stirred for 30 minutes. Ethanethiol (0.1 mL, 1.3 mmol) was added to the above reaction mixture at 0° C. and the reaction mixture was heated at 60° C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to 25°C. Cold water (150 mL) was added to the reaction mixture and the resulting precipitate was filtered off, washed with water (10 mL) and dried under vacuum to give crude product. The crude product is purified by flash column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(2-(ethylthio)imidazo[1,2-a]pyridine-3- yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (0.25 g, 0.7 mmol, 78% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.85 (t, J = 1.0 Hz, 1H), 8.63-8.65 (m, 2H), 7.74 (dt, J = 9.0 , 1.1 Hz, 1 H), 7.50 (ddd, J = 9.0, 6.8, 1.2 Hz, 1 H), 7.08 (td, J = 6.8, 1.2 Hz, 1 H), 3.90 (s, 3H), 3.25 (q, J=7.3Hz, 2H), 1.23 (t, J=6.8Hz, 3H); ESI MS (m/z) 378.10 ( MH) ⁺ .

g) Step 7: 2-(2-(ethylsulfonyl)imidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b ] Pyridine:

2-(2-(ethylthio)imidazo[1,2-a]pyridin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b in dichloromethane (5 mL) ] To a solution of pyridine (0.2 g, 0.5 mmol) was added portionwise m-chloroperbenzoic acid (0.3 g, 1 mmol) at 0-5°C. The reaction mixture was stirred at 25° C. for 2 hours. After completion of the reaction, the reaction mixture was diluted with aqueous sodium thiosulfate and extracted with dichloromethane (15 mL). The dichloromethane extract was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 35% ethyl acetate in hexanes as eluent to give 2-(2-(ethylsulfonyl)imidazo[1,2-a]pyridine-3 -yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (0.1 g, 0.3 mmol, 67% yield) was obtained. ¹ H-NMR (400MHz, DMSO-d6) δ 8.93-8.93 (m, 1H), 8.73 (dd, J = 2.1, 0.6Hz, 1H), 8.47 (dt, J = 7.0, 1.1 Hz, 1H), 7.94 (dt, J = 9.2, 1.1 Hz, 1H), 7.68 (ddd, J = 9.0, 6.8, 1.2 Hz , 1H), 7.22 (td, J = 6.9, 1.1Hz, 1H), 3.86 (s, 3H), 3.49-3.52 (q, J = 6.8Hz, 2H) , 1.15-1.24 (t, J=7.6 Hz, 3H); ESI MS (m/z) 409.95 (MH) ⁺ .

Example 3: 2-(8-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 Synthesis of -b]pyridine (Compound No. 6):

a) Step 1: 3-bromo-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium:

To a stirred solution of 3-bromopyridine (12.4 mL, 127 mmol) in acetonitrile (200 mL) was added ethyl 2-bromoacetate (15.5 mL, 139 mmol) and the reaction mixture was heated to reflux for 16 hours. After completion of the reaction, the reaction mixture was cooled to 25° C., the resulting precipitate was filtered and 3-bromo-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium (30 g, 122 mmol, yield 97%) was obtained. ¹ H-NMR (400 MHz, chloroform-D) δ 9.56 (m, 1H), 9.35 (s, 1H), 8.62 (d, J = 8.3 Hz, 1H), 6.28 (s, 2H), 4.36 (q, J=7.1 Hz, 3H), 1.33-1.4 (t, J=7.2 Hz, 3H); ESI MS (m/z) 243.85, 245. 85 [(MH) ⁺ Br ^79,81 ].

b) Step 2: Ethyl 6-bromo-2-fluoroindolizine-3-carboxylate and Ethyl 8-bromo-2-fluoroindolizine-3-carboxylate:

To a stirred solution of 3-bromo-1-(2-ethoxy-2-oxoethyl)pyridin-1-ium (3 g, 12.2 mmol) in N,N-dimethylformamide (80 mL) was added 2,2-difluorovinyl 4 - Methylbenzenesulfonate (1 g, 4.3 mmol), potassium carbonate (0.85 g, 6.1 mmol), and triethylamine (0.85 mL, 6.1 mmol) were added. The reaction mixture was heated at 70° C. for 16 hours. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (50 mL) was added to the above reaction mixture and extracted twice with ethyl acetate (200 mL). The combined ethyl acetate layers were washed with brine (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by reverse-phase preparative HPLC to give ethyl 6-bromo-2-fluoroindolizine-3-carboxylate (240 mg, 0.8 mmol, 14% yield) and 8-bromo-2-fluoroindo Ethyl lysine-3-carboxylate (160 mg, 0.56 mmol, 9%) was obtained.

i. Ethyl 6-bromo-2-fluoroindolizine-3-carboxylate: ¹ H-NMR (400 MHz, DMSO-d6) δ 9.37-9.47 (m, 1H), 7.63-7.71 (m, 1H), 7.35-7.41 (m, 1H), 6.58-6.69 (m, 1H), 4.35 (q, J = 7.1Hz, 2H), 1.35 (t, J=7.2 Hz, 3 H); ESI MS (m/z) 286.05, 288.05 [(MH) ⁺ Br ^79,81 ].

ii. Ethyl 8-bromo-2-fluoroindolizine-3-carboxylate: ¹ H-NMR (400 MHz, DMSO-d6) δ 9.28-9.40 (m, 1H), 7.58-7.64 (m, 1 H), 6.97 (t, J=7.2 Hz, 1 H), 6.57 (d, J=11.5 Hz, 1 H), 4.33 (q, J=7.2 Hz, 2 H), 1. 3 (t, J = 7.2 Hz, 3H); ESI MS (m/z) 286,288 [(MH) ^{+ Br79,81} ].

c) Step 3: 8-bromo-2-fluoro-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)indolizine-3-carboxamide:

Ethyl 6-bromo-2-fluoroindolizine-3-carboxylate (2.1 g, 7.3 mmol) and N-2-methyl-5-( 8-Bromo-2-fluoro-N-(2-(methylamino)- was obtained by reacting with trifluoromethyl)pyridine-2,3-diamine (1 g, 5.23 mmol) as the appropriate reactant. 5-(Trifluoromethyl)pyridin-3-yl)indolizine-3-carboxamide (1.3 g, 3 mmol, 41% yield) was obtained. ¹ H-NMR (400 MHz, chloroform-D) δ 9.62 (d, J = 7.0 Hz, 1 H), 8.37 (d, J = 0.9 Hz, 1 H), 7.72 (dd, J = 6 .7, 2.1 Hz, 1 H), 7.46-7.52 (m, 1 H), 7.33-7.38 (m, 1 H), 6.75 (t, J = 7.3 Hz, 1 H) , 6.49 (s, 1 H), 5.13 (d, J = 4.3 Hz, 1 H), 3.05-3.08 (d, J = 5.2 Hz, 3 H); ESI MS (m/z ) 430.75, 432.75 [(MH) ⁺ Br ^79,81 ].

d) Step 4: 2-(8-bromo-2-fluoroindolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

using 8-bromo-2-fluoro-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)indolizine-3-carboxamide (2.2 g, 5.10 mmol) 2-(8-bromo-2-fluoroindolizin-3-yl)-3-methyl-6-(trifluoromethyl)-, following the same synthetic procedure as described in step 4 of Example 34. 3H-imidazo[4,5-b]pyridine (1.8 g, 4.4 mmol, 85% yield) was obtained. ESI MS (m/z) 412.70, 414.70 [(MH) ^{+ Br79,81} ].

e) Step 5: 2-(8-bromo-2-(ethylthio)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-(8-bromo-2-fluoroindolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (100 mg, 0.2 mmol) was added to the appropriate As a starting material, 2-(8-bromo-2-(ethylthio)indolizin-3-yl)-3-methyl-6-(tri- Fluoromethyl)-3H-imidazo[4,5]-b]pyridine (50 mg, 0.1 mmol, 45% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.83 (d, J = 1.2 Hz, 1 H), 8.61 (d, J = 1.5 Hz, 1 H), 8.41 (d, J = 7 0 Hz, 1 H), 7.33 (dd, J=7.3, 0.6 Hz, 1 H), 6.83 (d, J=0.6 Hz, 1 H), 6.66 (t, J=7. 2 Hz, 1 H), 3.82 (s, 3 H), 2.98 (q, J = 7.3 Hz, 2 H), 1.18 (q, J = 7.1 Hz, 3 H); ESI MS (m/z ) 454.95, 456.95 [(MH) ⁺ Br ^79,81 ].

f) Step 6: 2-(8-bromo-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine:

2-(8-Bromo-2-(ethylthio)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- was prepared following the same synthetic procedure as described in Step 6 of Example 34. 2-(8-Bromo-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-( Trifluoromethyl)-3H-imidazo[4,5-b]pyridinepyridine (800 mg, 1.6 mmol, 89% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.89-8.93 (m, 1H), 8.55-8.72 (m, 1H), 8.12-8.23 (m, 1H), 7.50-7.57 (m, 1H), 7.11-7.26 (m, 1H), 6.75-6.85 (m, 1H), 3.72 (s, 3H), 3. 39-3.51 (q, J=6.8 Hz, 2H), 1.15 (t, J=7.1 Hz, 3H); ESI MS (m/z) 487.05, 489.05 [(MH) ⁺ Br ^79,81 ].

g) Step 7: 2-(8-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b]pyridine:

2-(8-bromo-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl) while following the same synthetic procedure as described in step 7 of Example 34 2-(8 -(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (65 mg, 0 .1 mmol, 38% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 8.73 (s, 1H), 8.22 (d, J = 7.1 Hz, 1H), 7.81 (s, 3H), 7.27 (d, J=6.8Hz, 1H), 6.99-7.13 (m, 2H), 3.73 (s, 3H), 3.40 (q, J=7. 2 Hz, 2 H), 1.11 (t, J=7.3 Hz, 3 H); ESI-MS (m/z) 553.15, 555.15 [(MH) ⁺ Cl ^35,37 ].

Example 4: 2-(6-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5 Synthesis of -b]pyridine (Compound No. 8):

Starting from ethyl 8-bromo-2-fluoroindolizine-3-carboxylate obtained in step 2 of Example 42, 2-(8-(3,5-dichlorophenyl)-2-(ethylsulfonyl)indolizine -3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine was prepared following the same sequence of steps 3-7 described for the synthesis of 2- (6-(3,5-)dichlorophenyl)-2-(ethylsulfonyl)indolizin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine Obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.92-8.93 (m, 1H), 8.71-8.71 (m, 1H), 8.55 (d, J = 0.7Hz, 1H ), 7.90-7.94 (m, 1H), 7.73-7.77 (m, 2H), 7.62 (m, 1H), 7.53 (dd, J = 9.4, 1 .6Hz, 1H), 7.01-7.28 (m, 1H), 3.75 (s, 3H), 3.33-3.42 (m, 2H), 1.15 (t, J = 6 .2 Hz, 3H); ESI MS (m/z) 553.00, 555.00 [(MH) ^{+ Cl35,37} ].

Example 5: 2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [ Synthesis of 4,5-b]pyridine (Compound No. 9):

a) Step 1: Ethyl 2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylate:

Ethyl 5-amino-3-(ethylthio)-1H-pyrazole-4-carboxylate (2 g, 9.3 mmol) in acetic acid (20 mL) [Acta Chimica Sinica 2003, 63, 855; Organic & Biomolecular Chemistry, 2010, 8 , 3394] and 2,4-pentanedione (1.15 mL, 11.15 mmol) was added 2 drops of concentrated sulfuric acid. The resulting mixture was heated at 50° C. for 15 minutes. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (5 mL) was added to the above reaction mixture and the reaction mixture was extracted with ethyl acetate (10 mL) three times. The combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by column chromatography on silica gel using 20% ethyl acetate in hexanes as eluent to give 2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidine Ethyl-3-carboxylate (2.0 g, 7.20 mmol, 77% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 7.04 (d, J = 0.7 Hz, 1 H), 4.25 (q, J = 7.1 Hz, 2 H), 3.17 (q, J = 7 .3Hz, 2H), 2.67-2.83 (m, 3H), 2.56 (d, J = 23.7Hz, 3H), 1.36-1.53 (m, 3H), 1.30 (q, J = 6.9 Hz, 3H); ESI MS (m/z) 280.20 (MH) ⁺ .

b) Step 2: 2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid:

Ethyl 2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylate (2.3 g, 8 .2 mmol) was added lithium hydroxide monohydrate (5.18 g, 123.0 mmol). The reaction mixture was stirred at 60° C. for 17 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to remove ethanol. The residue was treated with 1N hydrochloric acid solution and the resulting precipitate of 2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid (88 mg, 0.35 mmol, yield 59%) was filtered off, washed with water (10 mL) and dried under vacuum. ¹ H-NMR (400MHz, DMSO-d6) δ 12.16 (s, 1H), 7.02 (d, J = 0.7Hz, 1H), 3.15 (q, J = 7.3Hz, 2H), 2.67 (d, J = 0.9 Hz, 3H), 2.53 (s, 3H), 1.37 (t, J = 7.3 Hz, 3H); ESI MS (m/z) 252.15 ( MH) ⁺ .

c) Step 3: 2-(ethylthio)-5,7-dimethyl-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine- 3-carboxamide:

To a solution of 2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid (500 mg, 2 mmol) in anhydrous N,N-dimethylformamide (27 mL), 1-[ Bis(dimethylamino)methylene]-1H-1,2,3-triazole[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) (908 mg, 2.4 mmol) was added and the reaction mixture was brought to 0- Stir at 5° C. for 15 minutes. N-2-methyl-5-(trifluoromethyl)pyridine-2,3-diamine (761 mg, 4 mmol) and N,N-diisopropylethylamine (1 mL, 6 mmol) were then added to the above reaction mixture to was heated at 100° C. for 16 hours. After completion of the reaction, water (40 mL) was added to the reaction mixture, which was then extracted with ethyl acetate (30 mL) three times. The combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(ethylthio)-5,7-dimethyl-N-(2-(methylamino) -5-(trifluoromethyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (510 mg, 1.20 mmol, 60% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.27 (d, J = 1.3 Hz, 1H), 8.05-8.07 (m, 1H), 7. 14-7.28 (m, 1H), 6.80 (d, J = 4.9Hz, 1H), 3.22 (q, J = 7.3Hz, 2H), 2.92 (d, J = 4 .6Hz, 3H), 2.76 (d, J = 0.5Hz, 3H), 2.64 (s, 3H), 1.41 (t, J = 7.3Hz, 3H); z) 425.20 (MH) ⁺ .

d) Step 4: 2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo [4,5-b]pyridine:

2-(ethylthio)-5,7-dimethyl-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)pyrazolo [1 in N-methyl-2-pyrrolidone (8 mL) ,5-a]pyrimidine-3-carboxamide (380 mg, 0.90 mmol), p-toluenesulfonic acid monohydrate (511 mg, 2.7 mmol) was heated at 150° C. in a microwave oven under a nitrogen atmosphere. 0.5 hours of irradiation. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (50 mL) was added to the above reaction mixture followed by extraction with ethyl acetate (50 mL). The ethyl acetate layer was washed with water (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by flash column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5 -a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (194 mg, 0.5 mmol, 53% yield) was obtained. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.64 (d, J=1.2 Hz, 1 H), 8.31 (d, J=1.5 Hz, 1 H), 6.65 (d, J=0. 7 Hz, 1 H), 4.02 (s, 3 H), 3.29 (q, J = 7.4 Hz, 2 H), 2.79 (d, J = 0.7 Hz, 3 H), 2.57 (s, 3H), 1.46 (t, J=7.3 Hz, 3H); ESI MS (m/z) 407.10 (MH) ⁺ .

Example 6: 2-(2-(ethylsulfonyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo Synthesis of [4,5-b]pyridine (Compound No. 10):

2-(2-(ethylthio)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- in dichloromethane (8 mL) To a solution of imidazo[4,5-b]pyridine (165mg, 0.4mmol) m-chloroperbenzoic acid (255mg, 0.8mmol) was added in portions at 0-5°C. The reaction mixture was stirred at 25° C. for 5 hours. After completion of the reaction, the reaction mixture was diluted with aqueous sodium thiosulfate and extracted with dichloromethane (20 mL). The dichloromethane layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by flash column chromatography on silica gel using 60% ethyl acetate in hexanes as eluent to give 2-(2-(ethylsulfonyl)-5,7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (92 mg, 0.2 mmol, 52% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1 H), 8.61 (d, J = 2.0 Hz, 1 H), 7.36 (d, J = 1.0 Hz, 1 H), 3.78 (s, 3H), 3.73 (q, J=7.3Hz, 2H), 2.83 (s, 3H), 2.57 (s, 3H), 1.25 (t, J= 7.3 Hz, 3 H); ESI MS (m/z) 439.25 (MH) ⁺ .

Example 7: 2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H- Synthesis of imidazo[4,5-b]pyridine (Compound No. 19):

a) Step 1: Ethyl 2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate:

(E)-3-(dimethylamino)- 1-(4-Fluorophenyl)prop-2-en-1-one (1.7 g, 9 mmol) was added and the resulting mixture was heated at 50° C. for 2 hours. After completion of reaction, acetic acid was removed under reduced pressure to obtain crude product. The crude product is purified by column chromatography on silica gel using 30% ethyl acetate in hexanes as eluent to give 2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a ] to give ethyl pyrimidine-3-carboxylate (2.2 g, 6.37 mmol, 71% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 8.77 (d, J = 4.6 Hz, 1H), 8.20-8.25 (m, 2H), 7.44-7.49 (m, 2H) ), 7.42 (d, J = 4.6 Hz, 1 H), 4.30 (q, J = 7.1 Hz, 2 H), 3.09 (q, J = 7.3 Hz, 2 H), 1.33 (dt, J = 15.6, 7.2 Hz, 6H); ESI MS (m/z) 346.30 (MH) ⁺ .

b) Step 2: 2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid:

Ethyl 2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (2.2 g, 6.4 mmol) in a mixture of ethanol (30 mL) and water (30 mL) ) was added lithium hydroxide monohydrate (2.7 g, 63.7 mmol). The reaction mixture was stirred at 60° C. for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to remove ethanol. The residue was treated with 1N hydrochloric acid solution and the resulting precipitate of 2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (1.6 g, 5 mmol, Yield 79%) was filtered off, washed with water (10 mL) and dried under vacuum. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.44 (d, J = 4.6 Hz, 1 H), 8.28 (ddd, J = 12.1, 5.3, 3.2 Hz, 2 H), 7 .43-7.49 (m, 2H), 7.19 (d, J = 4.6Hz, 1H), 3.00 (q, J = 7.3Hz, 2H), 1.32 (t, J = 7.3 Hz, 3 H); ESI MS (m/z) 317.90 (M) ⁺ .

c) Step 3: 2-(ethylthio)-7-(4-fluorophenyl)-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)pyrazolo[1,5-a ] pyrimidine-3-carboxamide:

2 drops to a suspension of 2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (500 mg, 1.58 mmol) in anhydrous dichloromethane (15 mL). of N,N-dimethylformamide was added followed by oxalyl chloride (0.2 mL, 2.4 mmol) and the resulting reaction mixture was stirred at 25° C. for 4 hours. The reaction mixture was evaporated under reduced pressure at a bath temperature of 60°C. The resulting residue was dissolved in anhydrous dichloromethane (15 mL) and treated with N-2-methyl-5-(trifluoromethyl)pyridine-2,3-diamine (304 mg, 1.6 mmol) and triethylamine (0.9 mL, 6.5 mL). 6 mmol) was added dropwise at 0°C to a stirred solution. The reaction mixture was stirred at 25° C. for 16 hours. After completion of the reaction, water (40 mL) was added to the reaction mixture, which was then extracted with ethyl acetate (20 mL) three times. The combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(ethylthio)-7-(4-fluorophenyl)-N-(2-( Methylamino)-5-(trifluoromethyl)pyridin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (377 mg, 0.8 mmol, 49% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.51 (s, 1 H), 8.85 (d, J = 4.6 Hz, 1 H), 8.28-8.34 (m, 3 H), 7. 90 (d, J = 1.8Hz, 1H), 7.49-7.53 (m, 3H), 6.92 (d, J = 4.6Hz, 1H), 3.14 (q, J = 7 .2 Hz, 2 H), 2.89 (d, J=4.6 Hz, 3 H), 1.33-1.39 (m, 3 H); ESI MS (m/z) 490.95 (M) ⁺ .

d) Step 4: 2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - imidazo[4,5-b]pyridine:

2-(ethylthio)-7-(4-fluorophenyl)-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl) in N-methyl-2-pyrrolidone (8 mL) A mixture of pyrazolo[1,5-a]pyrimidine-3-carboxamide (377 mg, 0.8 mmol), p-toluenesulfonic acid monohydrate (439 mg, 2.3 mmol) was heated in a microwave oven at 150° C. under a nitrogen atmosphere. for 1.5 hours. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (50 mL) was added to the above reaction mixture followed by extraction with ethyl acetate (150 mL). The ethyl acetate layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1 ,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (185 mg, 0.4 mmol, 51% yield) was obtained. . ¹ H-NMR (400 MHz, DMSO-d6) δ 8.77 (q, J = 0.9 Hz, 1 H), 8.75 (d, J = 4.4 Hz, 1 H), 8.54-8.54 (m , 1H), 8.29-8.33 (m, 2H), 7.49-7.53 (m, 2H), 7.43 (d, J = 4.6Hz, 1H), 3.97 (s , 3H), 3.17 (q, J = 7.3 Hz, 2H), 1.36 (t, J = 7.3 Hz, 3H); ESI MS (m/z) 473.00 (MH) ⁺ .

Example 8: 2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine Synthesis of (Compound No. 22):

a) Step 1: Ethyl 2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylate:

To a stirred solution of ethyl 5-amino-3-(ethylthio)-1H-pyrazole-4-carboxylate (1.3 g, 6 mmol) in acetic acid (38 mL) was added 3-(dimethylamino)acrolein (0.9 mL, 9 .1 mmol) was added. The reaction mixture was stirred at 25° C. for 24 hours. After completion of the reaction, the reaction mixture was neutralized using saturated aqueous sodium bicarbonate and extracted with ethyl acetate (20 mL) three times. The combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography on silica gel using 30% ethyl acetate in hexanes as eluent to give ethyl 2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylate ( 0.9 g, 3.5 mmol, 57% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 9.18 (dd, J = 6.9, 1.7 Hz, 1 H), 8.74 (q, J = 1.9 Hz, 1 H), 7.20 (dd , J = 7.0, 4.3 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 3.16 (q, J = 7.3 Hz, 2H), 1.37 (t, J=7.3 Hz, 3H), 1.25-1.31 (m, 3H); ESI MS (m/z) 252.10 (MH) ⁺ .

b) Step 2: 2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid:

To a stirred suspension of ethyl 2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylate (0.9 g, 3.5 mmol) in a mixture of ethanol (50 mL) and water (50 mL) was added water. Lithium oxide monohydrate (1.45 g, 34.6 mmol) was added. The reaction mixture was stirred at 60° C. for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to remove ethanol. The residue was treated with 1N hydrochloric acid solution and the resulting precipitate of 2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.6 g, 2.8 mmol, 81% yield) was filtered off. Separated, washed with water (10 mL) and dried under vacuum. ¹ H-NMR (400MHz, DMSO-d6) δ 12.38 (s, 1H), 9.16 (dd, J = 7.0, 1.8Hz, 1H), 8.69 (q, J = 2.0Hz , 1H), 7.16 (dd, J = 6.7, 4.3Hz, 1H), 3.14 (q, J = 7.3Hz, 2H), 1.36 (t, J = 7.5Hz, 3H); ESI MS (m/z) 223.85 (M) ⁺ .

c) Step 3: 2-(ethylthio)-N-(5-(methylamino)-2-(trifluoromethyl)pyridin-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide:

To a suspension of 2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (325 mg, 1.5 mmol) in anhydrous dichloromethane (14 mL) was added 2 drops of N,N-dimethylformamide. was followed by the addition of oxalyl chloride (0.2 mL, 2.2 mmol) and the resulting mixture was stirred at 25° C. for 4 hours. The reaction mixture was evaporated under reduced pressure at a bath temperature of 60°C. The resulting residue was dissolved in anhydrous dichloromethane (14 mL) and treated with N-3-methyl-6-(trifluoromethyl)pyridine-3,4-diamine (278 mg, 1.5 mmol) and triethylamine (0.85 mL, 6.5 mL). 1 mmol) was added dropwise at 0°C to a stirred solution. The reaction mixture was stirred at 25° C. for 16 hours. After completion of the reaction, water (40 mL) was added to the reaction mixture and extracted with ethyl acetate (20 mL) three times. The combined ethyl acetate layers were dried over sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(ethylthio)-N-(5-(methylamino)-2-(trifluoro Methyl)pyridin-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (392 mg, 1 mmol, 68% yield) was obtained. ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.45 (d, J=6.8 Hz, 1 H), 8.26 (d, J=3.9 Hz, 1 H), 8.11 (d, J=6. 1Hz, 1H), 6.95 (s, 1H), 6.72 (dd, J = 6.8, 4.2Hz, 1H), 5.18-4.61 (2H), 3.35 (s, 3H), 3.21 (q, J=7.3 Hz, 2H), 1.41-1.44 (m, 3H); ESI MS (m/z) 397.05 (MH) ⁺ .

d) Step 4: 2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c] Pyridine:

2-(ethylthio)-N-(5-(methylamino)-2-(trifluoromethyl)pyridin-4-yl)pyrazolo[1,5-a]pyrimidine in N-methyl-2-pyrrolidone (9 mL) A mixture of -3-carboxamide (392 mg, 1 mmol), p-toluenesulfonic acid monohydrate (564 mg, 3 mmol) was irradiated in a microwave oven at 150° C. for 1.5 hours under nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to 25°C. Water (50 mL) was added to the above reaction mixture followed by extraction with ethyl acetate (150 mL). The ethyl acetate layer was washed with water (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 40% ethyl acetate in hexanes as eluent to give 2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidine-3- yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine (256 mg, 0.7 mmol, 68% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.27 (dd, J = 6.8, 1.7 Hz, 1H), 9.14 (s, 1H), 8.70 (dd, J = 4.3 , 1.6 Hz, 1 H), 8.19 (d, J = 0.7 Hz, 1 H), 7.21 (dd, J = 6.8, 4.2 Hz, 1 H), 4.01 (s, 3 H) , 3.22 (q, J=7.3 Hz, 2H), 1.32-1.38 (m, 3H); ESI MS (m/z) 378.90 (MH) ⁺ .

Example 9: 2-(2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c] Synthesis of Pyridine (Compound No. 23):

2-(2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c in dichloromethane (9 mL) ] To a solution of pyridine (187 mg, 0.5 mmol) was added portionwise m-chloroperbenzoic acid (262 mg, 1 mmol) at 0-5°C. The reaction mixture was stirred at 25° C. for 5 hours. After completion of the reaction, the reaction mixture was diluted with aqueous sodium thiosulfate and extracted with dichloromethane (20 mL). The dichloromethane extract was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 60% ethyl acetate in hexanes as eluent to give 2-(2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidine-3 -yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-c]pyridine (105 mg, 0.3 mmol, 52% yield) was obtained. ¹ H-NMR (400MHz, DMSO-d6) δ 9.50 (dd, J = 7.1, 1.7Hz, 1H), 9.22 (s, 1H), 8.87 (q, J = 2.0Hz , 1H), 8.25 (d, J = 0.7Hz, 1H), 7.51 (dd, J = 7.2, 4.0Hz, 1H), 3.90 (s, 3H), 3.74 (q, J = 7.4 Hz, 2H), 1.24 (t, J = 7.5 Hz, 3H) ESI MS (m/z) 411.05 (MH) ⁺ .

Example 10: 2-(2-(ethylsulfonyl)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H - Synthesis of imidazo[4,5-b]pyridine (Compound No. 25):

2-(2-(ethylthio)-7-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)- in dichloromethane (6 mL) To a solution of 3H-imidazo[4,5-b]pyridine (185 mg, 0.4 mmol) was added m-chloroperbenzoic acid (208 mg, 0.8 mmol) portionwise at 0-5°C. The reaction mixture was stirred at 25° C. for 5 hours. After completion of the reaction, the reaction mixture was diluted with aqueous sodium thiosulfate and extracted with dichloromethane (15 mL). The dichloromethane layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by flash column chromatography on silica gel using 60% ethyl acetate in hexanes as eluent to give 2-(2-(ethylsulfonyl)-7-(4-fluorophenyl)pyrazolo [ 1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (120 mg, 0.2 mmol, 61% yield) was obtained. rice field. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 4.6 Hz, 1 H), 8.85 (d, J = 1.5 Hz, 1 H), 8.63 (d, J = 1 .5Hz, 1H), 8.25-8.28 (m, 2H), 7.69 (d, J = 4.6Hz, 1H), 7.53-7.59 (m, 2H), 3.81 (s, 3H), 3.73 (q, J = 7.4 Hz, 2H), 1.26 (t, J = 7.3 Hz, 3H); ESI MS (m/z) 505.10 (MH) ⁺ .

Example 11: 2-(7-(3-chloro-5-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl )-3H-imidazo[4,5-b]pyridine (Compound No. 102) Synthesis:

a) Step 1: 2-Cyano-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)acetamide:

2-cyanoacetic acid (7 g, 82 mmol), N2-methyl-5-(trifluoromethyl)pyridine-2,3-diamine (12.58 g, 65.8 mmol), and hydroxybenzotriazole ( HOBt) (15.12 g, 99 mmol) was added with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl) (18.93 g, 99.0 mmol) and N,N-diisopropyl. Ethylamine (35.9 mL, 206 mmol) was added. The resulting mixture was stirred at 25° C. for 24 hours under a nitrogen atmosphere. After completion of the reaction, water (100 mL) was added to the above reaction mixture and the reaction mixture was extracted with ethyl acetate (100 mL) three times. The combined ethyl acetate layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by column chromatography on silica gel using 30% ethyl acetate in hexanes as eluent to give 2-cyano-N-(2-(methylamino)-5-(trifluoromethyl) Pyridin-3-yl)acetamide (11.8 g, 45.7 mmol, 55.5% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1 H), 8.26 (d, J = 1.0 Hz, 1 H), 7.64 (d, J = 2.4 Hz, 1 H), 6.94 (d, J=4.4 Hz, 1 H), 3.83 (d, J=17.6 Hz, 2 H), 2.87 (d, J=4.6 Hz, 3 H); ESI MS (m/ z) 258(M)+.

b) Step 2: 2-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetonitrile:

A solution of 2-cyano-N-(2-(methylamino)-5-(trifluoromethyl)pyridin-3-yl)acetamide (11.8 g, 45.7 mmol) in acetic acid (120 mL) was treated at 100° C. for 2 Heated for hours. After completion of the reaction, the reaction mixture was cooled to 25°C. The reaction mixture was concentrated under reduced pressure to remove acetic acid. Water (100 mL) was added to the above concentrated reaction mixture and the reaction mixture was extracted with ethyl acetate (75 mL) three times. The ethyl acetate layer was washed with water (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 15% ethyl acetate in hexanes as eluent to give 2-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4 ,5-b]pyridin-2-yl)acetonitrile (9.0 g, 37.5 mmol, 82% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 8.76 (t, J = 1.0 Hz, 1 H), 8.55-8.56 (m, 1 H), 4.69 (s, 2 H), 3. 82 (s, 3H); ESI MS (m/z) 240.95 (MH)+.

c) Step 3: 3,3-bis(ethylthio)-2-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)acrylonitrile

A stirred solution of 2-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetonitrile (8.8 g, 36.6 mmol) in acetonitrile (80 mL) To the solution was added potassium hydroxide (4.84 g, 73.3 mmol) at 25°C. The resulting reaction mixture was stirred at 25° C. for 1 hour. The reaction mixture was further cooled to −5° C. and carbon disulfide (2.2 mL, 36.6 mmol) was added dropwise over 10 minutes. The reaction mixture was stirred at -5°C for 1 hour. Further ethyl iodide (5.92 mL, 73.3 mmol) was added dropwise into the reaction mixture at 0° C. over 15 minutes. The reaction mixture was again stirred at 0° C. for 2 hours and left at 25° C. for 16 hours. The reaction mixture was concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel using 10% ethyl acetate in hexanes as eluent to give 3,3-bis(ethylthio)-2-(3-methyl-6-(tri Fluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)acrylonitrile (12.4 g, 33.3 mmol, 91% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.84 (q, J = 1.0 Hz, 1 H), 8.62 (q, J = 0.9 Hz, 1 H), 3.87 (s, 3 H), 3.25 (q, J = 7.3Hz, 2H), 2.84 (q, J = 7.4Hz, 2H), 1.37 (t, J = 7.2Hz, 3H), 1.14 (t , J=7.3 Hz, 3 H); ESI MS (m/z) 373.00 (MH)+.

d) Step 4: 3-(ethylthio)-4-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-pyrazol-5-amine

3,3-bis(ethylthio)-2-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine-2 in a mixture of acetonitrile (1 mL) and ethanol (2 mL) -yl)acrylonitrile (1 g, 2.69 mmol) was added hydrazine monohydrate (0.17 mL, 2.69 mmol (79% w/v)) dropwise at 0°C. The reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was diluted with ice-cold water (20 mL) to precipitate a solid. The precipitated solid was filtered, washed with water and dried under vacuum to give crude product. The crude product is purified by column chromatography on silica gel using 100% ethyl acetate as eluent to give 3-(ethylthio)-4-(3-methyl-6-(trifluoromethyl)-3H-imidazo [4,5-b]pyridin-2-yl)-1H-pyrazol-5-amine (720 mg, 2.1 mmol, 78% yield) was obtained. 1H-NMR (400 MHz, DMSO-D6) δ 12.01 (s, 1H), 8.66 (s, 1H), 8.37 (s, 1H), 5.75 (s, 2H), 3.77 ( s, 3H), 2.88 (q, J = 6.8 Hz, 2H), 1.15 (t, J = 6.8 Hz, 3H); ESI MS (m/z) 343.00 (MH) ⁺ .

e) Step 5: 2-(ethylthio)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a] Pyrimidin-7(4H)-one

3-(ethylthio)-4-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)-1H-pyrazol-5-amine in acetic acid (5 mL) (550 mg, 1.61 mmol) and its uncyclized intermediate was added methyl 3,3-dimethoxypropanoate (0.34 mL, 2.41 mmol). The reaction mixture was heated at 100° C. for 6 hours. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure to remove acetic acid. Water (20 mL) was added to the above concentrated reaction mixture and the reaction mixture was extracted with ethyl acetate (25 mL) three times. The ethyl acetate layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 5% methanol in dichloromethane as eluent to give 2-(ethylthio)-3-(3-methyl-6-(trifluoromethyl)- 3H-Imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-one (375 mg, 0.95 mmol, 59% yield) was obtained. ¹ H-NMR (400MHz, DMSO-d6) δ 12.40 (s, 1H), 8.80 (q, J = 0.9Hz, 1H), 8.56 (dd, J = 2.1, 0.6Hz , 1 H), 7.84 (d, J = 7.3 Hz, 1 H), 5.87 (d, J = 7.3 Hz, 1 H), 3.77 (s, 3 H), 3.16 (q, J = 7.3 Hz, 2H), 1.32 (t, J = 7.3 Hz, 3H); ESI MS (m/z) 395.00 (MH) + .

f) Step 6: 2-(7-bromo-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4, 5-b] pyridine

2-(ethylthio)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1,5-a in acetonitrile (28 mL) ]Pyrimidin-7(4H)-one (1.05 g, 2.66 mmol) was added to a stirred solution of potassium carbonate (1.10 g, 7.99 mmol) and phosphorus oxybromide (2.29 g, 7.99 mmol) in 25 °C. The reaction mixture was further heated at 95° C. for 4 hours. The reaction mixture was cooled to 0°C. The reaction mixture was diluted with an ice-water mixture (50 mL). The pH of the reaction mixture was adjusted to 7-8 by slow addition of saturated aqueous sodium bicarbonate. The reaction mixture was extracted with ethyl acetate (50 mL) three times. The ethyl acetate layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by flash column chromatography on silica gel using 50% ethyl acetate in hexanes as eluent to give 2-(7-bromo-2-(ethylthio)pyrazolo[1,5-a] Pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (980 mg, 2.14 mmol, 80% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.77 (t, J = 1.1 Hz, 1 H), 8.55 (d, J = 1.5 Hz, 1 H), 8.48 (d, J = 4 .6 Hz, 1 H), 7.65 (d, J = 4.6 Hz, 1 H), 3.92 (s, 3 H), 3.25 (q, J = 7.3 Hz, 2 H), 1.40 (t , J=7.3 Hz, 3H); ESI MS (m/z) 456.95, 458.95 (MH; ^Br79,81 )+

g) Step 7: 2-(7-(3-chloro-5-fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoro methyl)-3H-imidazo[4,5-b]pyridine

2-(7-bromo-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl) in a mixture of tetrahydrofuran (4 mL) and water (2 mL) )-3H-imidazo[4,5-b]pyridine (170 mg, 0.37 mmol) and (3-chloro-5-fluorophenyl)boronic acid (78 mg, 0.446 mmol) was added sodium carbonate (197 mg, 1 .86 mmol) was added. The reaction mixture was fully deoxygenated by subjecting it to vacuum/nitrogen cycles three times. Tetrakis(triphenylphosphine)palladium(0) (12.9 mg, 0.01 mmol) was added to the reaction mixture and heated at 85° C. for 4 hours. After completion of the reaction, the reaction mixture was cooled to 25° C. and filtered through a pad of celite. The filtrate is concentrated under reduced pressure and the crude product is purified by flash column chromatography on silica gel using 20% ethyl acetate in hexane as eluent to give 2-(7-(3-chloro-5- fluorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (120 mg, 0.24 mmol, 64% yield). ¹ H-NMR (400 MHz, DMSO-d6) δ 8.77-8.79 (m, 2H), 8.55 (d, J = 1.5 Hz, 1H), 8.23 (d, J = 1.5 Hz , 1H), 8.10 (dq, J = 9.7, 1.2Hz, 1H), 7.79 (dt, J = 8.8, 2.1Hz, 1H), 7.55 (d, J = 4.6 Hz, 1 H), 3.96 (s, 3 H), 3.16 (q, J = 7.3 Hz, 2 H), 1.40 (t, J = 7.2 Hz, 3 H); ESI MS (m /z) 506.95, 508.95 (MH ^{; Cl35,37} )+.

Example 12: 3-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2 ,4]triazolo[4,3-a]pyridine (Compound No. 111) Synthesis

a) Step 1: 2-hydrazinyl-5-(trifluoromethyl)pyridine:

To a stirred solution of 2-chloro-5-(trifluoromethyl)pyridine (10.0 g, 55.1 mmol) in ethanol was added hydrazine hydrate (5.18 g, 123 mmol). The resulting reaction mixture was stirred at 90° C. for 16 hours. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure to remove ethanol. Water (50 mL) was added to the above concentrated reaction mixture and the reaction mixture was extracted with ethyl acetate (200 mL) three times, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford 2-hydrazinyl-5-(trifluoromethyl). Pyridine (8.50 g, 48.00 mmol, 87% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.25 (d, J = 0.7 Hz, 2H), 7.68 (dd, J = 9.0, 2.4 Hz, 1H), 6.78 (d , J=9.0 Hz, 1 H), 4.32 (s, 2 H); ESI MS (m/z) 178.10 (MH) ⁺ .

b) Step 2: 7-(3,5-dichlorophenyl)-2-(ethylthio)-N′-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-3- Carbohydrazide:

To a stirred solution of 2-hydrazinyl-5-(trifluoromethyl)pyridine (0.80 g, 4.52 mmol) in N,N-dimethylformamide (8 mL) was added 7-(3,5-dichlorophenyl)-2-( Ethylthio)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (1.66 g, 4.52 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.29 g, 6.77 mmol) ), 1-hydroxybenzotriazole (0.91 g, 6.77 mmol), and N,N-diisopropylethylamine (1.75 mL, 13.55 mmol) were added at 0°C. The reaction mixture was stirred at 25° C. for 16 hours under a nitrogen atmosphere. After completion of the reaction, water (20 mL) was added to the reaction mixture and the resulting precipitate was filtered and dried under reduced pressure to give 7-(3,5-dichlorophenyl)-2-(ethylthio)-N′- (5-(Trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-3-carbohydrazide (1.2 g, 2.27 mmol, 50% yield) was obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H), 9.39 (s, 1H), 8.83 (dd, J = 11.9, 4.6 Hz, 1H), 8. 42 (d, J = 20.2Hz, 1H), 8.24-8.29 (m, 2H), 7.91-7.99 (m, 1H), 7.84 (dd, J = 8.9 , 2.1 Hz, 1 H), 7.58-7.61 (m, 1 H), 6.77 (d, J = 8.7 Hz, 1 H), 3.09 (q, J = 7.2 Hz, 2 H) , 1.40 (t, J=7.2 Hz, 3 H); ESI MS (m/z) 527.25 (MH) ⁺ .

c) Step 3: 3-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2 ,4]triazolo[4,3-a]pyridine:

7-(3,5-dichlorophenyl)-2-(ethylthio)-N′-(5-(trifluoromethyl)pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-3-carbohydrazide (1 g, 1.90 mmol) was added phosphoryl chloride (3 mL) and the resulting reaction mixture was heated at 90° C. for 6 hours. The reaction mixture was cooled at 25° C. and concentrated under reduced pressure. The reaction mixture was further cooled to 0° C. and the resulting mass was treated with saturated sodium bicarbonate solution to bring the pH to basic (pH 9). The resulting mixture was extracted with ethyl acetate (50 mL) three times. The combined ethyl acetate layers were dried over anhydrous sodium sulfate and concentrated under reduction to give crude product. The crude product is purified by column chromatography on silica gel using 25% ethyl acetate in hexanes as eluent to give 3-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1 ,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (500 mg, 0.98 mmol, 52% yield). rice field. ¹ H-NMR (400 MHz, DMSO-d6) δ 9.09 (d, J = 1.0 Hz, 1 H), 8.72 (d, J = 4.4 Hz, 1 H), 8.32 (d, J = 2 .0 Hz, 2 H), 8.09 (d, J = 9.8 Hz, 1 H), 7.96 (t, J = 2.0 Hz, 1 H), 7.68 (dd, J = 9.7, 1. 6 Hz, 1 H), 7.56-7.58 (m, 1 H), 3.17 (q, J = 7.3 Hz, 2 H), 1.42 (t, J = 7.3 Hz, 3 H); ESI MS (m/z) 508.70 (MH)+.

d) Step 4: 3-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1, 2,4]triazolo[4,3-a]pyridine:

3-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1, in dichloromethane (8 mL) To a solution of 2,4]triazolo[4,3-a]pyridine (0.35g, 0.68mmol) was added m-chloroperbenzoic acid (0.58g, 2.06mmol, 60%) at 0°C. The resulting reaction mixture was stirred at 25° C. for 16 hours. The reaction mixture was diluted with dichloromethane (20 mL) and washed twice with saturated aqueous sodium bicarbonate (20 mL) followed by water (10 mL). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give crude product. The crude product is purified by column chromatography on silica gel using 30% ethyl acetate in hexane as eluent to give 3-(7-(3,5-dichlorophenyl)-2-(ethylsulfonyl)pyrazolo [ 1,5-a]pyrimidin-3-yl)-6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (210 mg, 0.388 mmol, 56% yield) Obtained. ¹ H-NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 4.4 Hz, 2H), 8.24 (d, J = 1.7 Hz, 2H), 8.15 (d, J = 9 .5 Hz, 1 H), 8.01 (t, J = 2.0 Hz, 1 H), 7.82 (d, J = 4.6 Hz, 1 H), 7.74 (dd, J = 9.7, 1. 6 Hz, 1 H), 3.62 (q, J=7.3 Hz, 2 H), 1.27 (t, J=7.5 Hz, 3 H); ESI MS (m/z) 540.90 (MH)+.

Example 13: (7-(3,5-dichlorophenyl)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-2-yl)pyrazolo[1, Synthesis of 5-a]pyrimidin-2-yl)(ethyl)(imino)-λ ⁶ -sulfanone (Compound No. 135):

2-(7-(3,5-dichlorophenyl)-2-(ethylthio)pyrazolo[1,5-a]pyrimidin-3-yl)-3-methyl-6-(trifluoromethyl) in methanol (6 mL) To a stirred solution of -3H-imidazo[4,5-b]pyridine (312 mg, 0.60 mmol) and ammonium carbamate (140 mg, 1.79 mmol) was added iodobenzene diacetate (384 mg, 1.19 mmol) at 0°C. added. The resulting reaction mixture was stirred at 25° C. for 16 hours. The reaction mixture was concentrated under reduced pressure. The crude residue was diluted with water (20 mL) and the mixture was extracted three times with ethyl acetate (50 mL). The ethyl acetate layer was washed with water (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude product. The crude product was purified by preparative HPLC to give (7-(3,5-dichlorophenyl)-3-(3-methyl-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine- 2-yl)pyrazolo[1,5-a]pyrimidin-2-yl)(ethyl)(imino)-λ ⁶ -sulfanone (110 mg, 0.2 mmol, 44% yield) was obtained. 1H-NMR (400 MHz, DMSO-d6) δ 8.90 (d, J=4.4 Hz, 1 H), 8.84 (d, J=1.2 Hz, 1 H), 8.62 (t, J=1. 1 Hz, 1 H), 8.25 (d, J = 2.0 Hz, 2 H), 7.98 (t, J = 2.0 Hz, 1 H), 7.75 (d, J = 4.4 Hz, 1 H), 4.80 (s, 1H), 3.81 (s, 3H), 3.49-3.56 (m, 2H), 1.28 (t, J = 7.5 Hz, 3H); ESI MS (m /z) 554.00 (MH)+.

The following compounds (Table-1) were obtained using Schemes 1-23 or analogous procedures as described in the Examples.

Compound names are created using Chemdraw Professional 18.1

The following compounds (Table 2) can be obtained using Schemes 1-23 or analogous procedures described in the Examples.

Compound names are created using Chemdraw Professional 18.1

As described herein, compounds of formula (I) exhibit insecticidal activity exerted against a large number of insects that attack important agricultural crops. The compounds of the invention were evaluated for their activity as described in the following tests:

Biological example

Example A: Helicoverpa armigera

A dietary incorporation method was used in which the required amount of test compound was weighed, dissolved in a detergent solution, kept vortexed for 90 minutes for proper mixing, and then diluted with water to the desired test concentration. When the temperature reached approximately 50°C in the bioassay vessel, the solution was incorporated into the semi-synthetic diet. The diet and solution were stirred well for proper mixing and then cooled for 30 minutes. The solidified diet was cut into equal pieces and each piece was transferred to one cell of the bioassay tray. A single starved 3rd instar larva was released into each of these cells in a bioassay tray, each tray covered with a lid. Bioassay trays were maintained under laboratory conditions at a temperature of 25° C. and a relative humidity of 70%. Observations of dead, moribund, and live larvae were recorded 96 hours after larval release. Mortality was calculated by combining dead and moribund larvae and comparing the result to one untreated control. Compounds 15 21 25 26 27 28 32 39 83 87 90 91 93 97 99 101 102 103 104 109 118 120 126, and 136 showed greater than 70% mortality activity at 300 PPM.

Example B: Spodoptera litura

A dietary intake method was used in which the required amount of test compound was weighed, dissolved in a detergent solution, kept vortexed for 90 minutes for proper mixing, and then diluted with water to the desired test concentration. . When the temperature in the bioassay vessel reached approximately 50°C, the solution was incorporated into the semi-synthetic diet. The diet and solution were stirred well for proper mixing and allowed to cool for 30 minutes. The solidified diet was cut into equal pieces and each piece was transferred to one cell of the bioassay tray. A single starved 3rd instar larva was released into each of these cells in a bioassay tray and the tray was covered with a lid. Bioassay trays were maintained under laboratory conditions at a temperature of 25° C. and a relative humidity of 70%. Observations of dead, moribund, and live larvae were recorded 96 hours after larval release. Mortality was calculated by combining dead and moribund larvae and comparing the result to one untreated control. Compounds 15 21 25 26 37 63 83 87 90 93 101 103 118 126 129, and 134 showed greater than 70% mortality activity at 300 PPM.

Example C: Plutella xylostella

Weigh the required amount of compound, dissolve in a detergent solution, keep on vortex for 90 minutes at 2000 rpm with zirconia beads for proper mixing, then dilute with 0.01% Triton-X solution. A leaf immersion method was used in the test, where the desired test concentration was obtained. Cabbage leaves were immersed in the solution for 10 seconds, dried in the shade for 20 minutes, and then transferred to bioassay trays. One-second-old larvae were released into the cells of each bioassay tray and the tray was covered with a lid. The bioassay trays were maintained under laboratory conditions at a temperature of 25°C and a relative humidity of 70%. Observations of dead, moribund, and live larvae were recorded 72 hours after larval release. Mortality was calculated by combining dead and moribund larvae and comparing the result to one untreated control. compound 5 6 9 12 15 18 20 21 22 25 26 27 28 29 30 32 34 35 37 39 40 43 46 48 50 62 63 66 67 69 70 71 74 80 81 83 87 88 90 91 93 95 96 99 100 101 103 104 109 114 115 118 119 129 130 131 133 135 136, and 137 showed over 70% mortality activity at 300 PPM.

Example D: Bemisia tabaci
The required amount of test compound is weighed, dissolved in a detergent solution, kept on a vortex at 2000 rpm for 90 minutes using zirconia beads for proper mixing, and then with 0.01% Triton-X solution. A leaf immersion method was used for testing, with dilution to the desired test concentration. A cotton leaf was dipped into the solution for 10 seconds, dried in the shade for 20 minutes, and then kept in a glass unit while the leaf was submerged in water. A known number of freshly used adults were released and maintained in a plant growth chamber at a temperature of 25° C. and a relative humidity of 70%. Observations of dead, moribund, and live adults were recorded 72 hours after release. Mortality was calculated by combining dead and moribund adults and comparing the results to one untreated control. Compounds 22 and 119 showed greater than 70% mortality activity at 300 PPM.

Example E: Myzus persicae

The required amount of test compound is weighed, dissolved in a detergent solution, kept on a vortex at 2000 rpm for 90 minutes using zirconia beads for proper mixing, and then with 0.01% Triton-X solution. A leaf immersion method was used for testing, with dilution to the desired test concentration. Capsicum leaves were dipped into the solution for 10 seconds, dried in the shade for 20 minutes, and then kept in a glass unit while the leaves were submerged in water. A known number of third instar nymphs was released into glass units and maintained in a plant growth chamber at a temperature of 25° C. and a relative humidity of 70%. Observations of dead, dying, and live nymphs were recorded 72 hours after release. Mortality, dead and moribund nymphs were combined and calculated by comparing the results to one of the untreated controls. Compounds 9 14 16 22 23 50 71 104, and 131 showed efficacy with greater than 70% mortality at 300 PPM.

Example F: Nilaparvata lugens

The required amount of test compound is weighed, dissolved in a detergent solution, kept on a vortex at 2000 rpm for 90 minutes using zirconia beads for proper mixing, and then with 0.01% Triton-X solution. A seedling dipping method was used for testing, which diluted to the desired test concentration. Rice seedlings were dipped in the solution for 10 seconds, dried in the shade for 20 minutes, and then kept in glass tubes while the roots were submerged in water. A known number of third instar nymphs was released into test tubes, which were maintained in a plant growth chamber at a temperature of 25°C and a relative humidity of 75%. Observations of dead, dying, and live nymphs were recorded 72 hours after release. Mortality was calculated by combining dead and moribund nymphs and comparing the results to one untreated control. Compounds 1422 and 63 showed greater than 70% mortality activity at 300 PPM.

Having described the invention with reference to certain preferred embodiments, other embodiments will become apparent to those skilled in the art from consideration of the specification. It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the invention.