A PROCESS FOR THE SYNTHESIS OF ANTHRANYLIC DIAMIDE COMPOUNDS AND INTERMEDIATE COMPOUNDS THEREOF.

Abstract

The present invention discloses a process for the synthesis of an anthranilic diamide compound of formula (I), wherein R1, R2, R3a, R3b, R3c, R4, R5, R6, and Z are as defined in the detailed description. Process 5 comprises the step of obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), which is then converted into an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va). Furthermore, the compound of formula (VI) can optionally be synthesized from the compound of formula (IV, V, or Va).

Description

A PROCESS FOR THE SYNTHESIS OF ANTHRANYLIC DIAMIDE COMPOUNDS AND INTERMEDIATE COMPOUNDS THEREOF FIELD OF INVENTION: The present invention relates to a process for the synthesis of anthranilic diamide compounds. More particularly, the present invention relates to a process for the synthesis of anthranilic diamide compound of formula (I) from substituted aniline compound of formula (II). The present invention further relates to a process for the synthesis of intermediate compounds useful in the synthesis of compound of formula (I) from substituted aniline compound of formula (II). BACKGROUND OF THE INVENTION: Anthranilic diamides are a commercially important class of synthetic insecticides that bind to the ryanodine receptor with selective potency against insect forms of the receptor versus mammalian forms. The first commercially available anthranilic diamide of this class, chlorantraniliprole, has exceptional activity against lepidopteran pests. The second anthranilic diamide product in the same class, cyantraniliprole, has excellent cross-spectrum activity against a variety of insect orders, including lepidopteran and hemipteran pests. PCT publications WO2003015518, WO2003015519, WO2004067528, WO2005077934, and WO20100069502 disclose the use of anthranilic diamides for controlling invertebrate pests such as arthropods. These anthranilic diamide compounds can be prepared from 3,5-substituted 2-amino-A / -alkylbenzamide compounds as intermediates. PCT publication WO2013007603 discloses a process for the preparation of 2-amino-5-cyano-3-methyl(V-methyl)benzamide compounds from 2-amino-5-cyano-3-methylbenzoic acid esters. Furthermore, the synthesis of certain 3,5-substituted 2-amino-V-alkylbenzamide compounds and their usefulness as intermediates for preparing the corresponding anthranilic diamide insecticide compounds have been disclosed in documents WO2004067528, WO2006068669, WO2006062978, and WO2012103436. Furthermore, the process for the synthesis of cyano derivatives of anthranilic diamide compounds or cyano functions containing compounds RPRRCn / LZnZ / q / YIAI intermediates thereof are disclosed in PCT publications WO2008010897, WO2008070158, WO2009085816, WO2009061991, WO2009006061 and WO2008082502. However, the processes described in the aforementioned literature are laborious, and a simple, efficient, and industrially economical process for the preparation of anthranilic diamide compounds remains necessary. Therefore, the present invention provides a simple, environmentally friendly, and cost-effective process for the preparation of anthranilic diamide compounds and their intermediates. OBJECT OF THE INVENTION: The main objective of the present invention is to provide a simple, environmentally friendly and cost-effective process for the synthesis of anthranilic diamide compound of formula (I). Another objective of the present invention is to provide a process for the synthesis of anthranilic acid compound of formula (V) and anthranilic amide compound of formula (Va). Another objective of the present invention is to provide a process for the synthesis of an N-substituted anthranilic amide compound of formula (VI). SUMMARY OF THE INVENTION: Accordingly, the present invention provides a process for the synthesis of anthranilic diamide compound of formula (I), RPRRCn / LZnZ / q / YIAI Formula (I) where, R1 is C1-C4 alkyl or halogen; R2 is hydrogen, halogen or cyano; R3ay R3bsonindependently hydrogen, C1-C4 alkyl or C3-C6 cycloalkyl C1-C4 alkyl; > π N 3N — c R3ces hydrogen or C1-C4 alkyl;« £^3« N=\ N ''N R4 is halogen, CF3, OCF2H, OCH2CF3 or 'N; R5s is halogen; R6 is hydrogen or halogen; Z is CR7o N;y R7 is hydrogen or halogen, from substituted aniline compound of formula (II); π where, R1, R2 and R3 have the definition mentioned above. The process for the synthesis of the anthranilic diamide compound of formula (I) comprises a step of obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV) which is then converted into an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va). Finally, the compound of formula (VI) can optionally be synthesized from the compound of formula (IV or V or Va). In one embodiment, the present invention provides a process for the synthesis of an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va) from a substituted aniline compound of formula (II). In another embodiment, the present invention provides a process for the synthesis of an N-substituted anthranilic amide compound of formula (VI) from a substituted aniline compound of formula (II). DETAILED DESCRIPTION OF THE INVENTION: The definitions provided herein for the terminology used in this disclosure are for illustrative purposes only and are in no way intended to limit the scope of the invention disclosed herein. As used herein, the terms and expressions comprising, comprising, including, having, containing, characterized by, or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any explicitly stated limitations. For example, a composition, mixture, process, or method comprising a list of elements is not necessarily limited to those elements but may include other elements not expressly listed or inherent in that composition, mixture, process, or method. The transitional expression "consisting of" excludes any unspecified element, step, or ingredient. If it appears in a claim, it restricts the inclusion in the claim of materials other than those mentioned, except for impurities commonly associated with them. When the expression "consisting of" appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; it does not exclude other elements of the claim as a whole. The transitional expression "essentially consisting of" is used to define a composition or method that includes materials, steps, features, components, or elements, in addition to those explicitly disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel features of the claimed invention. The expression "essentially consisting of" occupies a middle ground between "comprising" and "consisting of." Furthermore, unless expressly stated otherwise, "or" refers to an inclusive "or" and not an exclusive "or." For example, a condition A or B is met if any of the following are true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present). Also, the indefinite articles a / one and a, when preceding an element or component of the present invention, are not intended to be restrictive in RPRRCn / LZnZ / q / YIAI regarding the number of cases (i.e., occurrences) of the element or component. Therefore, un / uno or una should be read in a way that includes at least one / ao and the singular word form of the element or component also includes the plural, unless the number is obviously singular. A carbon-based radical refers to a monovalent molecular component comprising a carbon atom that connects the radical to the rest of the chemical structure via a single bond. Carbon-based radicals may optionally comprise saturated, unsaturated, and aromatic groups, chains, rings, and ring systems, as well as heteroatoms. Although carbon radicals are not restricted to a particular size limit, in the context of the present invention, they typically comprise from 1 to 16 carbon atoms and from 0 to 3 heteroatoms. Of particular note are carbon-based radicals selected from Ci-Ce alkyl, Ci-Ce haloalkyl, and phenyl groups, optionally substituted with 1-3 substituents selected from CiC3 alkyl, halogen, and nitro groups. The meaning of different terms used in the description will be explained below. The term alkyl, used either alone or in compound words such as alkylthio, haloalkyl, -N(alkyl), alkylcarbonylalkyl, or alkylsulfonylamino, includes linear or branched C1-C24 alkyl groups, preferably C1-C15 alkyl groups, more preferably C1-C10 alkyl groups, and most preferably C1-C10 alkyl groups. 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, and 1,1-methylpentyl. -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 the different isomers.If the alkyl group is at the end of a compound substituent, such as in alkylcycloalkyl, the initial part of the compound substituent, for example, the cycloalkyl group, may be monosubstituted or polysubstituted in the same or different and independent manner with the alkyl group. The same applies to compound substituents in which other radicals, such as alkenyl, alkynyl, hydroxyl, halogen, or carbonyl, are present. RPRRCn / LZnZ / q / YIAI carbonyloxy and similar, are at the end. The term cycloalkyl means a ring-closed alkyl group. Representative examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. This definition also applies to a cycloalkyl group as part of a substituent compound, e.g., cycloalkylalkyl, etc., unless specifically defined elsewhere. The term cycloalkyl means alkyl group enclosed in a ring. Some representative examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term cycloalkylalkyl means a cycloalkyl substituent on an alkyl group; for example, cyclopropyl, cyclobutyl, or cyclopentyl are substituted at any carbon of the C1-C6 alkyl group. Representative examples of cycloalkylalkyl include cyclopropylmethyl and cyclopropylethyl. As used herein, the term "combine" refers to the act of mixing, blending, or combining in order to bring two or more chemical compounds into close contact to enhance a chemical reaction. For example, certain substrates, reagents, or ingredients, such as those described in the summary of the invention, are combined together in a suitable vessel, container, or apparatus so that the substrates, reagents, or ingredients can react chemically with each other to form a new product. To achieve at least one of the objectives defined above, the present invention provides a process for the synthesis of anthranilic diamide compound of formula (I), RPRRCn / LZnZ / q / YIAI Formula (I) where, R1 is C1-C4 alkyl or halogen; R2 is hydrogen, halogen or cyano; R3a and p3b are independently hydrogen, C1-C4 alkyl or C3-C6 cycloalkyl C1-C4 alkyl; R3ces hydrogen or C1-C4 alkyl; RPRRCn / LZnZ / q / YIAI cf3N=\ R4 is halogen, CF3, OCF2H, OCH2CF3 orN R5s is halogen; R6 is hydrogen, halogen; Z is CR7oN;y R7 is hydrogen or halogen, comprising the stages of: a) reacting an N-substituted anthranilic amide compound of formula (VI) with a pyrazolic acid compound of formula (Vil), obtaining the compound of formula (I), vi VII where, R8 is OH, Cl or C1-C4 O-alkyl; b) converting an anthranilic amide compound of formula (Va) into the N-substituted anthranilic amide compound of formula (VI) by any of the following steps: i. in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, ii. by using a suitable transamidation process, according to the reaction scheme shown below: I saw RPRRCn / LZnZ / q / YIAI convert an anthranilic acid compound of formula (V) into the N-substituted anthranilic amide compound of formula (VI) using a suitable amine of formula HN(R3a)(R3b) and a suitable coupling reagent, according to the reaction scheme depicted below: I saw c) converting a monocyano- or dicyano-substituted aniline compound of formula (IV) into the anthranilic acid compound of formula (V) or the anthranilic amide compound of formula (Va) optionally in the presence of a suitable base or a suitable acid, according to the reaction scheme shown below: or convert a monocyano- or dicyano-substituted aniline compound of formula (IV) into the N-substituted anthranilic amide compound of formula (VI) by any of the following reaction steps: i) in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, i) aminolysis using a suitable amine of formula HN(R3a)(R3b), according to the reaction scheme shown below: IV I saw RPRRCn / LZnZ / q / YIAI d) optionally, halogenate a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are hydrogen in the presence of a suitable halogenating agent, obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are halogen; e) converting a mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, into the monocyano- or dicyano-substituted aniline compound of formula (IV) using a suitable cyanation reagent, according to the reaction scheme shown below: f) converting a substituted aniline compound of formula (II) into the mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, using a suitable halogenating agent, according to the reaction scheme shown below: The compound with formula (Vil) can be synthesized using any of the methods known in the prior art. For example, the process for the synthesis of the compound with formula (Vil) is disclosed in documents WO2003015518, WO20030155519, WO2011157664 and WO2013030100. The compound of formula (VI) can be converted into the compound of formula (I) using any of the suitable methods known in the prior art. For example, the process for converting the compound of formula (VI) into the compound of formula (I) is disclosed in PCT patent applications WO2012103436, WO2008010897, and WO2006062978. The compound of formula (V) can be converted into a compound of formula (VI) using any of the suitable methods known in the prior art. For example, the process for converting a compound of formula (V) into a compound of formula (VI) is disclosed in prior art documents CN106146414A, WO2016131098, ACS Med. Chem. Lett., 2017, 8 (6), p. 678681 and Chem. Comm., 2018, 54, 12766-12769. In one embodiment, an anthranilic amide compound of formula (Va) is converted into an N-substituted anthranilic amide compound of formula (VI) by reacting said anthranilic amide compound of formula (Va) in a suitable solvent with a suitable alkylating agent in the presence of a suitable base at a temperature within the range of 20 °C to 100 °C for a period of 1 to 5 h, yielding an N-substituted anthranilic amide compound of formula (VI). The suitable alkylating agent used for the alkylation of said anthranilic amide compound of formula (Va) is selected from the group of alkyl halides, alkyl sulfates such as methyl sulfate, alkyl peroxides, alkylsilyl peroxides, trialkyl phosphates, alkyl aldehydes (by reductive N-alkylation), halomethyl-dialkylsilyl halides, metal complexes, or triethyloxonium tetrafluoroborate. Optionally, the alkylation reaction can be carried out by a reductive amination / alkylation process or by any other prior art means. Non-limiting examples of alkyl halides used for alkylation are selected from alkyl chlorides, alkyl bromides, alkyl iodides, alkyl fluorides, or mixtures thereof. In one embodiment, the halide of RPRRCn / LZnZ / q / YIAI alkyl is selected from the group consisting of alkyl chlorides, alkyl bromides, alkyl iodides and mixtures thereof. Preferably, the alkyl halide is an alkyl iodide selected from methyl iodide, ethyl iodide or propyl iodide. In another embodiment, said anthranilic amide compound of formula (Va) is converted into an N-substituted anthranilic amide compound of formula (VI) using suitable transamidation processes known in the prior art; for example, using transamidation processes such as those disclosed in J. Am. Chem. Soc., 2006, 128 (50), pp. 16406-16409; Advanced Synthesis & Catalysis, 2017, 359(2), pp. 302-313; RSC Adv., 2016,6, pp. 52724-52728 and Chemical Papers, 2015, 69 (11) 1421-1437. In another embodiment, the anthranilic acid compound of formula (V) is converted into an N-substituted anthranilic amide compound of formula (VI) by reacting said anthranilic acid compound of formula (V) with a suitable nucleophilic amine of formula HN(R3a)(R3b), wherein R3a and R3b are independently hydrogen, C1-C4 alkyl, or Cs-Ce-C1-C4 cycloalkyl, in the presence of a suitable coupling reagent. In a preferred embodiment, the suitable coupling reagent is selected from, but not limited to, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) hydrochloride, dicyclohexylcarbodiimide (DCC), 1-cyclohexyl-3-(2-morpholmoethyl)carbodiimide, 1,3-di-tert-butylcarbodiimide, 1-(dimethylaminopropyl)-3-ethylcarbodiimide thiodide, 1-tert-butyl-3-(1-diisopropylcarbodiimide, bis-(diphenylmethyl)carbodiimide, 1-tert-butyl-3-ethylcarbodiimide, 1-methyl-2-chloropyridine iodide, 2-ethoxy-1 -ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), BOP chloride and isobutyl chloroformate. The hydrolysis reaction is carried out by reacting a monocyano- or dicyano-substituted aniline compound of formula (IV) in a suitable solvent with a suitable base at a temperature within the range of 20 °C to 120 °C for a period of 8 to 18 h, yielding an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va). The suitable base useful for converting a monocyano- or dicyano-substituted aniline compound of formula (IV) into an anthranilic acid compound of formula (V) or into an anthranilic amide compound of formula (Va) includes, but is not RPRRCn / LZnZ / q / YIAI limitation, inorganic or organic bases. An inorganic base is preferably selected from the group comprising ammonia, alkali or alkaline earth metal hydroxide, carbonate, bicarbonate and the like, wherein the alkali and alkaline earth metal is selected from the group comprising lithium, sodium, potassium, rubidium, cesium, calcium, magnesium, barium and the like, or mixtures thereof. The organic base is preferably selected from the group comprising amines such as methylamine, dimethylamine, diethylamine, triethylamine, diisopropylamine, diisopropylethylamine, pyridine, alkylated and dialkylated pyridines, dimethylaminopyridine, piperidine and the like, or mixtures thereof. The suitable acid useful for converting a monocyano- or dicyano-substituted aniline compound of formula (IV) into an anthranilic acid compound of formula (V) or into an anthranilic amide compound of formula (Va) includes, but is not limited to, an inorganic compound (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, etc.), an organic acid (e.g., formic acid, acetic acid, trifluoroacetic acid, propionic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc.), an acidic ion-exchange resin, and the like. In one embodiment, the monocyano- or dicyano-substituted aniline compound of formula (IV) is converted into an N-substituted anthranilic amide compound of formula (VI) using aminolysis of said monocyano- or dicyano-substituted aniline compound of formula (IV) with a suitable amine of formula HN(R3a)(R3b), wherein R3a and R3b are independently selected from hydrogen, C1-C4 alkyl, or Cs-Ce-C1-C4 cycloalkyl. In one embodiment, the cyanation reaction is carried out by reacting a mono-, di- or tri-halogenated aniline compound of formula (III) with a suitable cyanation reagent by means of a classical nucleophilic substitution reaction or by means of a coupling reaction using a suitable metal catalyst, preferably a palladium catalyst and a suitable ligand at a temperature within the range of 80 °C to 170 °C for a period of 4 to 16 h, producing a monocyano- or dicyano-substituted aniline compound of formula (IV). The suitable metallic catalyst is selected from, but not limited to, copper (0), copper (I) acetate, copper (I) bromide, copper (I) chloride, copper (I) iodide, copper (I) oxide, copper (II) trifluoromethanesulfonate, acetate of RPRRCn / LZnZ / q / YIAI copper (II), copper (II) bromide, copper (II) chloride, copper (II) iodide, copper (II) oxide, NaX, KX, CuX2, MgX2, CsX or ZnX2; wherein X is Cl, Br, I or F. In another embodiment, the suitable metallic catalyst is a palladium catalyst selected from, but not limited to, palladium(II) acetate, palladium chloride, palladium bromide, palladium iodide, dichlorobis(benzonitrile)palladium(II), dichlorobis(acetonitrile)palladium(II), (pi-cinnamyl)palladium(II) chloride dimer or the like; metallic palladium; palladium / carbon; a zero-valent palladium such as bis(benzalacetone)palladium(0), tris(dibenzylideneacetone)dipalladium(0) or the like; a complex of a divalent to zero valency palladium with a ligand that will be described later (e.g., tetrakis(triphenylphosphine)palladium, bis(tri-tert-butylphosphine)palladium, bis(triphenylphosphine)palladium dichloride, 1,1'bis(diphenylphosphine)ferrocenepalladium dichloride, 1,1'bis(diphenylphosphine)ferrocenepalladium dichloride complex, 1,2bis(diphenylphosphine)ethanepalladium dichloride), or the like. El ligando adecuado usado se selecciona entre, pero sin limitación, ligando de alquilfosfina tal como trimetilfosfina, trietilfosfina, tri-n-butilfosfina, di-tercbutilmetilfosfina, tri-terc-butilfosfina, triciclohexilfosfina, butil-di-1-adamantilfosfina, bencildi-1-adamantilfosfina o similares; un ligando de alquilfosfonio tal como tetrafluoroborato de tri-n-butilfosfonio, tetrafluoroborato de tri-terc-butilfosfonio, tetrafluoroborato de di-íerc-butilmetilfosfonio, tetrafluoroborato de triciclohexilfosfonio o similares; an arylphosphine ligand such as triphenylphosphine, trio-tolylphosphine, tri-p-tolylphosphine, tri(2-furyl)phosphine, tri(2-thienyl)phosphine, or similar; a bidentate phosphine ligand such as 1,2-bis(diphenylphosphino)ethane, 1,2bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)butane, a, a'-bis(di-tert-butylphosphino)-o-xylene, or similar;a phosphine ligand of the ferrocene type such as 1,1'-bis(d¡phen¡lfosph¡no)ferrocene, 1,1'-bis(di-terc-but¡lfosph¡no)ferrocene, 1,1'bis(di¡soprop¡lfosph¡no)ferrocene, 1,2,3,4,5-pentaphenyl-1 '-(di-ercbutylphosphino)ferrocene or similar; a phosphine ligand of the biaryl type such as 2,2'-bis(diphenylphosphine)-1,1'-binaphthyl, 2,2'-bis(di-p-tolylphosphine)-1, V-binaphthyl, 2'bis[di(3,5-xylyl)phosphine]-1,1'-binaphthyl, 2,2'-bis(diphenylphosphine)-1,1'-biphenyl, 2-di-terc-butylphosphine-1,1'-binaphthyl, 2-(di-erc-butylphosphine)-1,1'-biphenyl, 2-di-erc-butylphosphine2'-( / V,A / -d¡methylamino)b¡phenyl, 2-di-terc-butylphosphine-2'-met¡lb¡phenyl, 2(d¡c¡clohex¡lfhosphine)biphenyl, 2-(dic¡clohex¡lfhosphine)-2,6'-dimethox¡-1,1'-biphenyl, 2(dic¡clohex¡lfosf¡no)-2'-( / V,A / -d¡met¡lam¡no)b¡phen¡lo, 2-(dicyclohex¡lfosf¡no)-2'RPRRCn / LZnZ / q / YIAI methylbiphenyl, 2-(dicyclohexylphosf¡no) ino)-2',4',6'-tri-isoprop¡l-1,1'-biphenyl, 2(difen¡lfosf¡no)-2'-(A / ,A / -d¡met¡lam¡no)biphen¡lo or similar;a pyrrole-type phosphine ligand such as / V-phenyl-2-(d-tert-butylphosphino)pyrrole, A / -phenyl-2(dicyclohexylphosphino)pyrrole or the like; a diphenyl ether type phosphine ligand such as 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene, bis(2-diphenylphosphinophenyl)ether or the like; a carbene ligand such as 1,3-bis(2,6diisopropylphen¡l)-4,5-dihydro¡midazolium tetrafluoroborate, 1,3-bis(2,β-d¡soprop¡lfen¡l)-4,5-dihydro¡midazolium chloride, 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazolium or the like.; In a preferred embodiment, the cyanation reaction is carried out by reacting a mono-, di- or tri-halogenated aniline compound of formula (III) in a suitable solvent with a suitable cyanation reagent at a temperature in the range of 110 °C to 170 °C for a period of 4 to 8 h, giving a monocyano- or dicyano-substituted aniline compound of formula (IV). The said suitable cyanation reagent useful for converting the mono-, di- or tri-halogenated aniline compound of formula (III) into the mono- or dicyano-substituted aniline compound of formula (IV) includes, but is not limited to, alkali metal cyanides, tere-butyl isocyanide, ethyl cyanoacetate, 2-chlorobenzyl thiocyanate, benzyl thiocyanate, dimethylmalononitrile, ptoluenesulfonylmethyl isocyanide, trimethylsilyl cyanide, cyanohydrin, acetone cyanohydrin, diethyl cyanophosphonate, 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate and alkali metal hexacyanoferrates (II). Preferably, the metal cyanide reagent is selected from sodium cyanide, cuprous cyanide, zinc cyanide, nickel cyanide, iron(III) cyanide, potassium cyanide, acetone cyanohydrin, sodium(II) hexacyanoferrate, and potassium(II) hexacyanoferrate.More preferably, the metal cyanide reagent is selected from either sodium cyanide or cuprous cyanide. The halogenation reaction is carried out by reacting the substituted aniline compound of formula (II) in a suitable solvent with bromine, chlorine or iodine in the presence or absence of sodium bromide or calcium bromide at a temperature in the range of 0 °C to 50 °C for a period of 30 min to 2 h producing mono-, di- or tri-halogenated aniline compound of formula (III). Halogenation as described in the present invention is carried out RPRRCn / LZnZ / q / YIAI in the presence of a suitable halogenation reagent including, but not limited to, HX, NaX, KX, CuX2, MgX2, CsX, ZnX2, SOCl2, SO2CI2, COCl2, X2, C(=O)(OCl3)2, β-BuOCI, NaOCI, chloramine-T, β-halosuccinamides, POX3, PX3, PXs or metal halides; wherein X is Cl, Br, I or F. The suitable solvents used in any of the stages of the process of the present invention are selected from aliphatic, alicyclic, or aromatic halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane, or trichloroethane; ethers such as diethyl ether, diisopropyl ether, ferc-methyl butyl ether, ferc-methyl amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane, or anisole; nitriles such as acetonitrile, propionitrile, n- or β-butyronitrile, or benzonitrile; amides such as β,α-dimethylformamide, β,α-dimethylacetamide, N-methylformanilide, β-methylpyrrolidone, or hexamethylphosphoric triamide; sulfoxides such as dimethyl sulfoxide or sulfones such as sulfolane; alcohols such as methanol, ethanol, isopropanol, polyethylene glycols; water or mixtures thereof. In one embodiment, the anthranilic acid compound of formula (V) or the anthranilic amide compound of formula (Va) can be isolated. In another embodiment of the present invention, the anthranilic acid compound of formula (V) is reacted with a compound of formula (Vil), yielding a compound of formula (VIII) which is then reacted with an amine, yielding the anthranilic diamide compound of formula (I). RPRRCn / LZnZ / q / YIAI where R1, R2, R3a, R3b, R3c, R4, R5, R6, R8 and Z are as defined above in this document. In another embodiment of the present invention, the present invention provides a process for the synthesis of an N-substituted anthranilic acid compound of formula (VI), RPRRCn / LZnZ / q / YIAI T νκ R1R3c VI where R1, R2, R3ay, and R3bson are as defined above, comprising the stages of: a) converting an anthranilic amide compound of formula (Va) into an N-substituted anthranilic amide compound of formula (VI) by any of the following steps: iii. in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, iv. by using a suitable transamidation process, according to the reaction scheme shown below: oo Va VI Or convert an anthranilic acid compound of formula (V) into an N-substituted anthranilic amide compound of formula (VI) using a suitable amine of formula HN(R3a)(R3b) and a suitable coupling reagent, according to the reaction scheme shown below: b) converting a monocyano- or dicyano-substituted aniline compound of formula (IV) into the anthranilic acid compound of formula (V) or the anthranilic amide compound of formula (Va) optionally in the presence of a suitable base or a suitable acid, according to the reaction scheme shown below: RPRRCn / LZnZ / q / YIAI or convert a monocyano- or dicyano-substituted aniline compound of formula (IV) into the N-substituted anthranilic amide compound of formula (VI) by any of the following reaction steps: i) in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, i) aminolysis using a suitable amine of formula HN(R3a)(R3b) according to the reaction scheme shown below: IV c) optionally, halogenate a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are hydrogen in the presence of a suitable halogenating agent, obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are halogen; d) converting a mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, into the monocyano- or dicyano-substituted aniline compound of formula (IV) using a suitable cyanation reagent, according to the reaction scheme shown below: RPRRCn / LZnZ / q / YIAI e) converting a substituted aniline compound of formula (II) into the mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, using a suitable halogenating agent, according to the reaction scheme shown below: In another embodiment, the present invention provides a process for the synthesis of an anthranilic acid compound of formula (V) or an anthranilic amide compound 10 of formula (Va), R2, where R1, R2, R3ay comprises the stages of: R3bson as defined above, which a) converting a monocyano- or dicyano-substituted aniline compound of formula (IV) into an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va) optionally in the presence of a suitable base or a suitable acid, according to the reaction scheme shown below: RPRRCn / LZnZ / q / YIAI or converting a monocyano- or dicyano-substituted aniline compound of formula (IV) into an N-substituted anthranilic amide compound of formula (VI) by any of the following reaction steps: i) in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, i) aminolysis using a suitable amine of formula HN(R3a)(R3b), according to the reaction scheme shown below: IV vi b) optionally, halogenate a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are hydrogen in the presence of a suitable halogenating agent, obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are halogen; c) converting a mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, into the monocyano- or dicyano-substituted aniline compound of formula (IV) using a suitable cyanation reagent, according to the reaction scheme shown below: III RPRRCn / IZnZ / q / YIAI d) converting a substituted aniline compound of formula (II) into the mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, using a suitable halogenating agent, according to the reaction scheme shown below: In another embodiment, the present invention provides a process for converting a mono-, di- or tri-halogenated aniline compound of formula (III-a), wherein X is Cl, into the monocyano- or dicyano-substituted aniline compound of formula (IV-a or IV-b) using a suitable cyanation reagent and a suitable metal catalyst, according to the reaction scheme depicted below, IV-b In another embodiment, the present invention provides a process for converting a dicyano-substituted aniline compound of formula (IV-a) into an anthranilic acid compound of formula (Va) or into an anthranilic amide compound of formula (V-aa) or into a compound of formula (Vl-a) by using a suitable reagent such as a suitable alkylating reagent or a suitable amine, according to the reaction scheme depicted below, RPRRCn / LZnZ / q / YIAI The process for the synthesis of the anthranilic diamide compound of formula (I) as disclosed in the present invention is as depicted in Scheme 1 below: Scheme: 1 where, R1, R2, R3a, R3b, R3c, R4, R5, R6, R7, R8 and Z are as defined above. In a preferred embodiment, the present invention provides a process for preparing anthranilic diamide of formula I where, R1es CH3, Br or Cl; R2esCN, Bro Cl; R3aes H and R3bes methyl or 1-cyclopropyl ethyl; Rrecs H; RPRRCn / LZnZ / q / YIAI R4es Br oN' R5es Cl; R6 is H or Cl; and Z is N. In another embodiment, the present invention provides a process for preparing a compound of formula VI I saw where, R1es CH3, BroCI; R2esCN, Bro Cl; R3aes H and R3bes methyl or 1-cyclopropyl ethyl; Rrecces H. The processes as disclosed in the present invention are preferably carried out in batches. However, continuous reaction steps are also possible. The processes as disclosed in the present invention can be carried out in the absence of a solvent or in the presence of one or more suitable solvents. The optional solvent must be resistant to oxidation (i.e., a solvent whose oxidation rate is substantially slower than that of compounds of formula I to VII is preferred) and suitable for suspending or preferably dissolving the reagents. Any expert in the field knows the best way to handle reaction mixtures after the respective reactions have been completed. In one embodiment, the treatment is usually carried out by isolating the product by filtration and, optionally, washing with solvent, and optionally, drying the product if necessary. The process steps according to the invention are generally carried out under atmospheric pressure. Alternatively, however, it is also possible to work under vacuum or pressure. Without further elaboration, it is believed that any person skilled in the art using the foregoing description can utilize the present invention to its fullest extent. Therefore, the following examples should be interpreted as merely illustrative and not limiting disclosure in any way. Examples: The compound of formula (V) can be converted into a compound of formula (VI) using any of the methods known in the prior art and as disclosed in these prior art documents CN106146414A, WO2016131098, ACS Med. Chem. Lett., 2017, 8 (6), pp. 678-681 and Chem. Commun., 2018,54, 12766-12769. The compound of formula (VI) is converted into a compound of formula (I) using any of the methods known in the prior art and as disclosed in PCT patent applications WO2012103436, WO2008010897 and WO2006062978. Example 1: Synthesis of 2-amino-3-bromo-5-chlorobenzoic acid Stage 1 Stage 2 Stage 3 Stage 3 RPRRCn / LZnZ / q / YIAI a) Step-1: Synthesis of 2,6-dibromo-4-chloroaniline To a stirred solution of sodium bromide (1.7 g, 16.5 mmol) in water (10 mL), bromine (0.9 mL, 16.5 mmol) was added at 25 °C. The resulting solution was added dropwise to 4-chloroaniline (1 g, 7.8 mmol) at 25 °C. Once the reaction was complete, the reaction mixture was filtered, the resulting solid was washed successively with water (50 mL) and a 10% aqueous sodium thiosulfate solution (20 mL), and dried under reduced pressure, yielding 2,6-dibromo-4-chloroaniline (2.2 g, 7.9 mmol, 100% yield). 1H NMR (400 MHz, DMSO-cfeJ δ 7.54 (s, 2H), 5.49 (s, 2H). b) Step-2: Synthesis of 2-amino-3-bromo-5-chlorobenzonitrile To a stirred solution of 2,6-dibromo-4-chloroammna (1.0 g, 3.5 mmol) in N-methylpyrrolidone (1.6 mL), cuprous cyanide (0.3 g, 3.8 mmol) was added, and the reaction mixture was stirred at 150°C for 1 h. After the reaction was complete, the reaction mixture was diluted with a mixture of ethyl acetate (10 mL) and water (10 mL) and filtered through a Celite bed. The filtrate was diluted with ice-cold water (10 mL) and extracted twice with ethyl acetate (20 mL). The combined ethyl acetate layers were dried on anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by ultrafast chromatography using ethyl acetate and hexane as eluent, yielding 2-amino-3-bromo-5-chlorobenzonitrile (0.52 g, 2.2 mmol, 64% yield). 1H NMR (400 MHz, CHLOROFORM-D) δ 7.81 (d, J = 2.4 Hz, 1 H), 7.68 (d, J=2.4 Hz, 1 H), 6.26 (s, 2H). c) Step-3: Synthesis of 2-amino-3-bromo-5-chlorobenzoic acid A solution of 2-amino-3-bromo-5-chlorobenzonitrile (0.2 g, 0.9 mmol) in ethanol (2 mL) was added to an aqueous solution of sodium hydroxide (0.1 g, 2.6 mmol), and the mixture was stirred for 16 h at 100 °C. After the reaction was complete, volatile substances were removed from the reaction mixture, and the reaction mixture was diluted with water and acidified to pH 3.0 using 2 M aqueous hydrochloric acid. The precipitate was filtered and dried, yielding 2-amino-3-bromo-5-chlorobenzoic acid (160 mg, 0.6 mmol, 74% yield). 1H NMR (400 MHz, DMSO-c / 6J δ 13.33 (sa, 1H), 7.75 (d, J = 2.4 Hz, 1H), 7.72 (d, J = 2.4 Hz, 1H), 6.83 (s, 2H), CLEM: [249.85]M H. Example 2: Synthesis of 2-amino-5-cyano- / V,3-dimethylbenzamide: Stage - b3 Stage - c4 Stage - d a) Step-1: Synthesis of 2,4-dibromo-6-methylaniline: To a solution of sodium bromide (19.2 g, 187 mmol) in water (50 mL), bromine was added at 25 °C. The resulting solution was added dropwise to o-toluidine (10.3 mL, 93 mmol) at 10 °C. The reaction mixture was stirred for 30 min at 10 °C. After the reaction was complete, the reaction mixture was diluted with water (50 mL), filtered, and the resulting solid was washed successively with water and a 10% aqueous sodium thiosulfate solution and dried under reduced pressure, yielding 2,4-dibromo-6-methylaniline (23 g, 87 mmol, 93% yield). 1H NMR (400 MHz, DMSO-cfe) δ 7.44-7.34 (1 H), 7.20-7.11 (1 H), 4.46-4.20 (sa, 2H). b) Step-2: Synthesis of 4-amino-5-methylisophthalonitrile: (i) To a stirred solution of 2,4-dibromo-6-methylaniline (20 g, 75 mmol) in N-methylpyrrolidone (60 mL), cuprous cyanide (20 g, 151 mmol) was added, and the reaction mixture was stirred at 150 °C for 6 h. After the reaction was complete, the reaction mixture was diluted with a mixture of 30% aqueous ammonium hydroxide solution (50 mL) and ethyl acetate (100 mL), and stirred for 1 h. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined ethyl acetate layers were washed successively with water (50 mL) and brine solution (50 mL). The ethyl acetate layer was dried on anhydrous sodium sulfate and concentrated under reduced pressure, yielding 4-amino-5-methylisophthalonitryl (8.7 g, 55.4 mmol, 73% yield). CLEM:

[156] MH, 1H NMR (400 MHz, DMSO-cfe) δ 7.87 (d, J= 1.8 Hz, 1H), 7.56 (d, J = 0.9 Hz, 1H), 6.75 (s, 2H), 2.10 (s, 3H). i) To a stirred mixture of 2,4-dibromo-6-methylaniline (1.0 g, 3.77 mmol), potassium iodide (0.25 g, 1.510 mmol), copper(I) iodide (0.14 g, 0.755 mmol), and potassium ferricyanide (1.243 g, 3.77 mmol) in polyethylene glycol (PEG) (10 mL), a solution of sym-dimethylethylenediamine (1.016 mL, 9.44 mmol) in polyethylene glycol (PEG) (5 mL) was added under a nitrogen atmosphere. The reaction mixture was heated to 175 °C for 4 h. Once the reaction was complete, the reaction mixture was diluted in ethyl acetate (80 mL), and washed with water (2 x 70 mL) and a saturated ammonium chloride solution (3 x 70 mL). The combined ethyl acetate layers were dried on sodium sulfate, concentrated under reduced pressure to the crude product, and crystallized in ethanol, yielding pure 4-amino-5-methylisophthalonitrile (350 mg, 2,22.1 mmol, 67% yield). iii) The reaction mixture of 2,4-dibromo-6-methylan¡line (50 g, 189 mmol), / V, / V-dimethylformamide (100 mi), potassium ferrocyanide (27.8 g, 75 mmol), sodium carbonate (20 g, 189 mmol), was heated. 2-dicyclohex¡lphosphino-2',4',6'tri-iso-propyl-1,1'-biphenyl (9 g, 18.87 mmol) and bis(dibenc¡l¡denoacetone)palladium (5.43 g, 9.44 mmol) up to 130 °C during RPRRCn / LZnZ / q / YIAI h. Once the reaction was complete, the reaction mixture was cooled to 25 °C, filtered through a Celite bed, and washed with dichloromethane. The filtrate was concentrated under reduced pressure, yielding a crude product, which was then dissolved in dichloromethane. tert-Butyl methyl ether was added to this mixture, and the mixture was stirred at 25 °C for 2 h. The mixture was filtered, and the solid residue was stirred in ethanol (30 mL) at 10–15 °C for 5 h and filtered again, yielding 17 g of pure product. The two filtrates were then mixed, concentrated, and purified by ultrafast column chromatography, yielding a slightly impure second batch, which was stirred again in ethanol (7 mL) for 16 h, yielding 6 g of pure product. (HPLP purity 89%), 4-amino-5methylisophthalonitrile 23 g, 146 mmol, yield 78%). MS: m / z = 156.00 [MH], 1H NMR (400 MHz, CDCI3) δ 7.85 (d, J = 2.0 Hz, 1 H), 7.53 (d, J = 0.8 Hz, 1 H), 6.73 (s, 2H), 2.07 (s, 3H).。 iv) The reaction mixture of 2,4-dibromo-6-methylaniline (10 g, 37.7 mmol), potassium ferrocyanide (6.38 g, 15.10 mmol), palladium II acetate (1.729 g, 3.77 mmol) and sodium acetate (6.19 g, 75 mmol) was heated in N,N-dimethylformamide (70 ml) to 150 °C for 18 h. After the reaction was complete, the solvent was removed under reduced pressure; the crude product was diluted in ethyl acetate (500 ml), filtered through Celite and washed with ethyl acetate and water (300 ml). The filtrate was washed with a saturated solution of sodium bicarbonate (2 x 200 ml) and brine (2 x 200 ml), dried over sodium sulfate, and concentrated, yielding the crude compound (15 g). Ethanol (100 ml) was added to the crude compound, and the mixture was stirred for 16 h. The mixture was cooled to 0 °C and filtered, yielding pure 4-amino-5-methylisophthalonitril (4.6 g; 29.3 mmol, 78% yield). (v) To a stirred mixture of 2,4-dibromo-6-methylaniline (0.600 g, 2.265 mmol), sodium cyanide (NaCN) (0.222 g, 4.53 mmol), copper(I) iodide (0.129 g, 0.679 mmol), and potassium iodide (0.226 g, 1.359 mmol) in xylene (3 mL), a solution of sym-dimethylethylenediamine (0.600 g, 2.265 mmol) in xylene (0.5 mL) was added under a nitrogen atmosphere. The reaction was heated at 175 °C for 16 h, then the mixture was diluted in ethyl acetate (70 mL) and water (75 mL), and the separated organic layer was washed with a saturated solution of sodium chloride. RPRRCn / LZnZ / q / YIAI ammonium (50 ml), saturated sodium bicarbonate solution (50 ml) and brine (50 ml). The organic layer was dried on sodium sulfate and concentrated, obtaining crude material (0.685 g), which was purified by ultrafast column chromatography, obtaining the pure 4-amino-5-methylisophthalonitrile product (0.085 g, 0.541 mmol, 24% yield). vi) To a stirred solution of 2,4-dibromo-6-methylaniline (0.500 g, 1.887 mmol) in β-methyl-2-pyrrolidinone (5 mL), copper(I) cyanide (0.340 g, 3.79 mmol) was added. The reaction mixture was stirred at 160 °C for 16 h. After the reaction was complete, the reaction mixture was diluted with a 30% aqueous ammonia solution (50 mL) and ethyl acetate (300 mL), and stirred further for 1 h. The reaction mixture was extracted using ethyl acetate (50 ml), washed with water (30 ml) and brine (30 ml) and evaporated to dryness, obtaining the desired product, purification in dichloromethane and diethyl ether, obtaining 4-amino-5-methylisosphthalonityl (0.200 g, 1.272 mmol, yield of 67%). c) Step-3: Synthesis of 2-amino-5-cyano-3-methylbenzamide: A reaction mixture of aqueous sodium hydroxide (0.5 g, 12.7 mmol) and 4-amino-5-methylisophthalonitryl (2 g, 12.7 mmol) was stirred in ethanol (15 ml) at 70 °C for 4 h. After the reaction was complete, the reaction mixture was diluted with ice water (30 ml) and the resulting precipitate was filtered, washed with water (20 ml) and dried under reduced pressure, yielding 2-amino-5-cyano-3-methylbenzamide (1.6 g, 9.13 mmol, 72% yield) as a whitish solid. 1H NMR (400 MHz, DMSO-d6) δ 7.97-7.90 (sa, 1H), 7.89-7.84 (m, 1 H), 7.45-7.37 (m, 1 H), 7.36-7.22 (sa, 3H), 2.08 (s, 3H), CLEM: [363.8]M H. d) Step-4: 2-amino-5-cyano-A / ,3-dimethylbenzamide To a mixture of 2-amino-5-cyano-3-methylbenzamide (200 mg, 1.1 mmol) and cesium carbonate (446 mg, 1.4 mmol) in dimethylformamide (2 mL), methyl iodide was added, and the reaction mixture was stirred for 2 h at 60 °C in a sealed tube. After the reaction was complete, the reaction mixture was diluted with ethyl acetate (20 mL) and washed twice with brine solution (20 mL). The ethyl acetate layer was dried on anhydrous sodium sulfate and concentrated under reduced pressure, yielding a crude product, which was purified by ultrafast chromatography using ethyl acetate and hexane as the eluent, yielding 2-amino-5-cyano-3-methylbenzamide (86 mg, 0.5 mmol, RPRRCn / LZnZ / q / YIAI performance of 40%). 1H NMR (400 MHz, DMSO-cfe? δ 8.50-8.35 (1H), 7.897.75 (1H), 7.51-7.37 (1H), 7.25-7.09 (2H), 2.79-2.68 (3H), 2.15-2.05 (3H), CLEM: [463.8]MH. Example 3: Synthesis of 2-amino-3-bromo-5-chlorobenzoic 3 4 Stage 1 Stage 2 Stage 3 RPRRCn / LZnZ / q / YIAI a) Step-1: Synthesis of 2-amino-5-chlorobenzonitrile To a stirred solution of 2-bromo-4-chloroaniline (20 g, 97 mmol) in N-methyl-2-pyrrolidone (70 mL), cuprous cyanide (19.14 g, 145 mmol) was added. The resulting reaction mixture was stirred at 140 °C for 5 h. After the reaction was complete, the reaction mixture was cooled to 25 °C and poured over water (250 mL). The resulting solid was filtered and washed with water and an aqueous sodium bicarbonate solution. The crude product was dissolved in ethyl acetate (100 mL) and subsequently washed with water (30 mL), aqueous ammonium hydroxide (30 mL), and brine solution (30 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate was ground with hexane and dried under reduced pressure, yielding 2-amino-5-chlorobenzonitrile (11.8 g, 77 mmol, 80% yield). 1H NMR (400 MHz, DMSO-de,) δ 7.47 (d, J = 2.4 Hz, 1H), 7.31 (dd, J = 9.2; 2.4 Hz, 1H), 6.77-6.79 (m, 1H), 6.22 (s, 2H), CGEM: [206,9]. b) Step-2: Synthesis of 2-amino-3-bromo-5-chlorobenzonitrile To a stirred solution of sodium bromide (0.7 g, 7.2 mmol) in water (10 mL), bromine (0.4 mL, 7.2 mmol) was added dropwise at 25 °C. To this solution, 2-amino-5-chlorobenzenitrile (1 g, 6.55 mmol) was added and the mixture was stirred at 25 °C for 30 min. After the reaction was complete, the reaction mixture was filtered, washed with water and a 10% aqueous sodium thiosulfate solution (20 mL), and dried under reduced pressure, yielding 2-amino-3-bromo-5-chlorobenzenitrile (1.4 g, 6.05 mmol, 92% yield). 1H NMR (400 MHz, DMSO-de) δ 7.82 (d, J = 2.4 Hz, 1 H), 7.66 (d, J = 2.4 Hz, 1 H), 6.27 (s, 2H), CGEM: [231.8]. c) Stage-3: Synthesis of 2-amino-3-bromo-5-chlorobenzoic acid A stirred suspension of 2-amino-3-bromo-5-chlorobenzonitrile (1.4 g, mmol) in ethanol (8 ml) was mixed with a solution of sodium hydroxide (0.7 g, 18.1 mmol) in water (8 ml), and stirred at 100 °C for 16 h. After the reaction was complete, the reaction mixture was concentrated under reduced pressure, yielding a semi-solid, which was diluted with water and acidified with 10% aqueous hydrochloric acid, obtaining the desired crude product as a solid, which was filtered and dried, yielding 2-amino-3-bromo-5-chlorobenzoic acid (1.48 g, 5.9 mmol, 98% yield). 1H NMR (400 MHz, DMSO-a and δ 13.28 (s, 1H), 7.74 (d, J = 2.4 Hz, 1H), 7.72 (d, J = 2.4 Hz, 1H), 6.77 (s, 2H), CLEM: [249.85]M+2. Example 4: Synthesis of 4-amino-5-methylisophthalonitrile: i) To a mixture of 2,4-dichloro-6-methylaniline (2.0 g, 11.36 mmol), [(cinnamyl)PdCl]2 (0.063 g, 0.11 mmol), 2-dicyclohexylphosphino-2',4',6'-tri-isopropyl-1,1'-biphenyl (0.162 g, 0.34 mmol) and / V,A / -diisopropylethylamine (9.92 ml, 56.8 1 mmol), n-butanol (20 ml) was added under an argon atmosphere. The reaction mixture was purged with argon for 10 min. The reaction mixture was then heated to 80 °C, followed by the addition of acetone cyanohydrin (2.079 ml, 22.72 mmol) diluted in n-butanol (20 ml) for a period of 3 h. Once the reaction was complete, the reaction mixture was cooled to 25 °C and concentrated under reduced pressure, obtaining the crude product, which was then washed with ice water (20 ml), the resulting precipitate was filtered and dried, yielding 4-amino5-methylisophthalonitrile (1.5 g, 9.54 mmol, 84% yield). 1H NMR (400 MHz, DMSO-cy6; δ: 7.89 (d, J = 1.7 Hz, 1H), 7.57 (d, J = 1.7 Hz, 1H), 6.76 (s, 2H), 2.10 (s, 3H). CGEM: 157.1. (i) To a mixture of 2,4-dichloro-6-methylaniline (10 g, 56.8 mmol), [(cinnamyl)PdCl]2 (0.31 g, 0.56 mmol), 2-dicyclohexylphosphino-2',4',6'-tri-isopropyl-1,1'-biphenyl (0.81 g, 1.7 mmol), A / , / V-diisopropylethylamine (DIPEA) (49.6 ml, 284 mmol), n-butan-1-ol (100 ml) was added under an argon atmosphere. The reaction mixture was purged with argon for 10 min. The reaction mixture was then heated to 85 °C, followed by the addition of acetone cyanohydrin (8.32 ml, 91 mmol) diluted in n-butanol (100 ml) for a period of 5 h. Once the reaction was complete, the reaction mixture was cooled to 25 °C and concentrated under reduced pressure, yielding the crude product, which was purified with CombiFlash using 0-60% ethyl acetate in hexane as the RPRRCn / LZnZ / q / YIAI eluent, obtaining 2-amino-5-chloro-3-methylbenzonitrite (2.6 g, 15.61 mmol, yield of 27%) and 4-amino-5-methylisophthalonite (4.5 g, 28.6 mmol, yield of 50%). 2-Amino-5-chloro-3-methylbenzonitrilo: RMN de1H (400 MHz, DMSO-afe) δ 7.39 (d, J = 1.6 Hz, 1H), 7.27 (d, J = 2.0 Hz, 1H), 5.93 (s, 2H), 2.11 (s, 3H). CGEM: 166.1; 4-amino-5-methyl-3-methylbenzonitrilo: RMN de1H (400 MHz, DMSOd6) δ: 7.89 (d, J = 1.7 Hz, 1H), 7.57 (d, J = 1.7 Hz, 1H), 6.76 (s, 2H), 2.10 (s, 3H). CGEM: 157.1. iii) To a mixture of 2,4-dichloro-6-methylaniline (100 g, 568 mmol), [(cinnamyl)PdCl]2 (1.57 g, 2.84 mmol), 2-dichlorohexylphosphine-2',4',6'-tri-isopropyl-1,1'-biphenyl (1.57 g, 2.84 mmol), and / V,A / -diisopropylethylamine (DIPEA) (496 mL, 2.84 mol), n-butanol (1000 mL) was added under a nitrogen atmosphere. The reaction mixture was then purged with nitrogen for 10 min. The reaction mixture was heated to 85 °C, followed by the addition of acetone cyanohydrin (83 mL, 909 mmol) to n-butanol (500 mL) for a period of 5 h. Once the reaction was complete, the reaction mixture was cooled to 25 °C. The solvent was evaporated under reduced pressure, yielding the crude residue, which was then washed with ice-cold water (2000 ml). The resulting solid was filtered and dried, yielding a crude product.The crude product obtained was dissolved in hot ethanol (1000 ml) and cooled. The solid precipitate was filtered and dried, yielding 4-amino-5-methylisophthalonitrile (28 g, 178 mmol, 31% yield). The filtrate was concentrated under reduced pressure and dissolved again in hot ethanol (500 ml), cooled, and filtered, yielding a mixture of products in solid form (20 g). The filtrate was concentrated, yielding 2-amino-5-chloro-3-methylbenzonitrile (37 g, 222 mmol, 39% yield). 2-Amino-5-chloro-3-methylbenzonitrile: 1H NMR (400 MHz, DMSO-cfe) δ: 7.39 (d, J = 1.6 Hz, 1H), 7.27 (d, J = 2.0 Hz, 1H), 5.93 (s, 2H), 2.11 (s, 3H). CGEM: 166.1; 4-amino-5-methylisophthalonitrile: 1H NMR (400 MHz, DMSOd6) δ: 7.89 (d, J = 1.7 Hz, 1H), 7.57 (d, J = 1.7 Hz, 1H), 6.76 (s, 2H), 2.10 (s, 3H). CGEM: 157.1.

Claims

1. A process for the synthesis of a compound of formula (I), wherein, R1 is C1-C4 alkyl or halogen; R2 is hydrogen, halogen or cyano; R3a and R3b are independently hydrogen, C1-C4 alkyl or C3-C6 cycloalkyl; R3c is independently hydrogen or C1-C4 alkyl; R4 is halogen, CF3, OCF2H, OCH2CF3 or R5 is halogen; R6 is hydrogen, halogen; Z is CR7 or N; and R7 is hydrogen or halogen, comprising the steps of: a) reacting an N-substituted anthranilic amide compound of formula (VI) with a pyrazolic acid compound of formula (Vil), yielding the compound of formula (I), RPRRCn / LZnZ / q / YIAI, wherein R8 is OH, Cl, or C1-C4 O-alkyl; b) converting an anthranilic amide compound of formula (Va) into the N-substituted anthranilic amide compound of formula (VI) by any of the following steps: i. in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, ii. by using a process ofsuitable transamidation, according to the reaction scheme shown below: or convert an anthranilic acid compound of formula (V) into the N-substituted anthranilic amide compound of formula (VI) using a suitable amine of formula HN(R3a)(R3b) and a coupling reagent according to the reaction scheme shown below: c) convert a monocyano- or dicyano-substituted aniline compound of formula (IV) into the anthranilic acid compound of formula (V) or the anthranilic amide compound of formula (Va) optionally in the presence of a suitable base or a suitable acid according to the reaction scheme shown below: RPRRCn / LZnZ / q / YIAI or convert a monocyano- or dicyano-substituted aniline compound of formula (IV) into the N-substituted anthranilic amide compound of formula (VI) by any of the following reaction steps: i) in the presence of a suitable base or a suitable acid and asuitable alkylation reagent, i) aminolysis using a suitable amine of formula HN(R3a)(R3b) according to the reaction scheme shown below: rv d) optionally, halogenate a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are hydrogen in the presence of a suitable halogenating agent, obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are halogen; e) converting a mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, into the monocyano- or dicyano-substituted aniline compound of formula (IV) using a suitable cyanating reagent according to the reaction scheme shown below: III RPRRCn / LZnZ / q / YIAI f) converting a substituted aniline compound of formula (II) into the mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, using a suitable halogenating agent,according to the reaction scheme shown below:

2. A process for the synthesis of a compound of formula (VI), or R3a H .I R3b R1 R3c VI wherein, R1 is C1-C4 alkyl or halogen; R2 is hydrogen, halogen or cyano; R3a and R3b are independently hydrogen, C1-C4 alkyl or C3-C6 cycloalkyl C1-C4 alkyl; R3c is hydrogen or C1-C4 alkyl; comprising the steps of: a) converting an anthranilic amide compound of formula (Va) into an N-substituted anthranilic amide compound of formula (VI) by any of the following steps: i. in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, i. by using a suitable transamidation process, according to the following reaction scheme: RPRRCn / LZnZ / q / YIAI convert an anthranilic acid compound of formula (V) into an N-substituted anthranilic amide compound of formula (VI) using a suitable amine of formula HN(R3a)(R3b) and a suitable coupling reagent,according to the reaction scheme shown below: b) converting a monocyano- or dicyan-substituted aniline compound of formula (IV) into the anthranilic acid compound of formula (V) or the anthranilic amide compound of formula (Va) optionally in the presence of a suitable base or a suitable acid, according to the reaction scheme shown below: converting a monocyano- or dicyan-substituted aniline compound of formula (IV) into the N-substituted anthranilic amide compound of formula (VI) by any of the following reaction steps: i) in the presence of a suitable base or a suitable acid and a suitable alkylating reagent, i) aminolysis using a suitable amine of formula HN(R3a)(R3b) according to the reaction scheme shown below: IV vi RPRRCn / LZnZ / q / YIAI c) optionally, halogenating a monocyano- or dicyan-substituted aniline compound of formula (IV),where R1 and / or R2 are hydrogen in the presence of a suitable halogenating agent, obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), where R1 and / or R2 are halogen; d) converting a mono-, di- or tri-halogenated aniline compound of formula (III), where X is a halogen, into the monocyano- or dicyano-substituted aniline compound of formula (IV) using a suitable cyanation reagent according to the reaction scheme shown below: e) converting a substituted aniline compound of formula (II) into the mono-, di- or tri-halogenated aniline compound of formula (III), where X is a halogen, using a suitable halogenating agent, according to the reaction scheme shown below: RPRRCn / LZnZ / q / YIAI, 3. A process for the synthesis of an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va), wherein R1 is C1-C4 alkyl or halogen; R2 is hydrogen, halogen, or cyano; R3c is hydrogen or C1-C4 alkyl; comprising the steps of: a) converting a monocyano- or dicyan-substituted aniline compound of formula (IV) into an anthranilic acid compound of formula (V) or an anthranilic amide compound of formula (Va), optionally in the presence of a suitable base or a suitable acid according to the reaction scheme shown below; or converting a monocyano- or dicyan-substituted aniline compound of formula (IV) into an N-substituted anthranilic amide compound of formula (VI) by any of the following reaction steps: i) in the presence of a suitable base or a suitable acid and a suitable alkylating reagent,i) aminolysis using a suitable amine of formula HN(R3a)(R3b) according to the reaction scheme shown below: vi RPRRCn / LZnZ / q / YIAI b) optionally, halogenate a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are hydrogen in the presence of a suitable halogenating agent, obtaining a monocyano- or dicyano-substituted aniline compound of formula (IV), wherein R1 and / or R2 are halogen; c) converting a mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, into the monocyano- or dicyano-substituted aniline compound of formula (IV) using a suitable cyanating reagent, according to the reaction scheme shown below: d) converting a substituted aniline compound of formula (II) into the mono-, di- or tri-halogenated aniline compound of formula (III), wherein X is a halogen, using a suitable halogenating agent,according to the reaction scheme shown below: π III, 4. The process according to claim 1 or 2 or 3, wherein said process comprises the conversion of a mono-, di- or trihalogenated aniline compound of formula (III-a), wherein X is Cl, into the monocyano- or dicyano-substituted aniline compound of formula (IV-a or IV-b) by using a suitable cyanation reagent, according to the reaction scheme shown below: III-a RPRRCn / LZnZ / q / YIAI 5. The process according to claim 1, 2, or 3, wherein said process comprises the conversion of a dicyano-substituted aniline compound of formula (IV-a) into an anthranilic acid compound of formula (Va) or into an anthranilic amide compound of formula (V-aa) or into a compound of formula (Vl-a) according to the reaction scheme shown below: IV-a V-aa Vl-a 6. The process according to claim 1 or 2 or 3, wherein said suitable cyanidation reagent is selected from alkali metal cyanides, tere-butyl isocyanide, ethyl cyanoacetate, 2-chlorobenzyl thiocyanate, benzyl thiocyanate, dimethylmalononitrile, ptoluenesulfonylmethyl isocyanide, trimethylsilyl cyanide, cyanohydrin, acetone cyanohydrin, diethyl cyanophosphonate, 1-cyano-4-(dimethylamino)pyridinium tetrafluoroborate or alkali (II) metal hexacyanoferrates.

7. The process according to claim 6, wherein said suitable cyanation reagent is selected from sodium cyanide, cuprous cyanide, zinc cyanide, nickel cyanide, iron(III) cyanide, potassium cyanide, sodium(II) hexacyanoferrate, potassium(II) hexacyanoferrate, and acetone cyanohydrin.

8. The process according to claim 1 or 2 or 3, wherein said suitable halogenating reagent is selected from HX, NaX, KX, CuX2, MgX2, CsX, ZnX2, SOCl2, SO2Cl2, COCl2, X2, C(=O)(OCI3)2, f-BuOCI, NaOCI, chloramine-T, / V-halosuccinamides, POX3, PX3, PX5 or metal halides; wherein X is Cl, Br, I or F.

9. The process according to claim 1 or 2 or 3, wherein said suitable solvent is selected from chlorobenzene, dichlorobenzene, dichloromethane, chloroform, tetrachloromethane, dichloroethane, trichloroethane, diethyl ether, diisopropyl ether, tert-butyl methyl ether, tert-amyl methyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane, anisole, acetonitrile, propionitrile, n- or n-butyronitrile, benzonitrile, α,α-dimethylformamide, N,N-dimethylacetamide, β-methylformanilide, β-methylpyrrolidone, hexamethylphosphoric triamide, dimethyl sulfoxide, sulfones, sulfolane, methanol, ethanol, isopropanol, water or mixtures thereof.

10. The process according to claim 1 or 2 or 3, wherein said suitable alkylating agent is selected from the group of alkyl halides, alkyl sulfates, alkyl peroxides, alkylsilyl peroxides, trialkyl phosphates, alkyl aldehydes (by reductive N-alkylation), halomethyl-dialkylsilyl halides, metal complexes or triethyloxonium tetrafluoroborate.

11. The process according to claim 10, wherein said alkyl halides are selected from alkyl chlorides, alkyl bromides, alkyl iodides, alkyl fluorides or mixtures thereof.

12. The process according to claim 11, wherein said alkyl halide is an alkyl iodide selected from methyl iodide, ethyl iodide, or propyl iodide. RPRRCn / LZnZ / q / YIAI 13. The process according to claim 1, wherein said suitable coupling reagent is selected from 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), dicyclohexylcarbodiimide (DCC), 1-cyclohexyl-3-(2-morpholmoethyl)carbodiimide, 1,3-di-tert-butylcarbodiimide, 1-(dimethylaminopropyl)-3-ethylcarbodiimide methyl iodide, 1-tert-butyl-3-(1-lyphenylmethyl)carbodiimide, 1,3-diisopropylcarbodiimide, bis-(diphenylmethyl)carbodiimide, 1-tert-butyl-3-ethylcarbodiimide, 1-methyl-2-chloropyridinium iodide, 2-ethoxy-1-ethoxycarbonyl1,2-dihydroquinoline (EEDQ), BOP chloride or isobutyl chloroformate.

14. The process according to claim 1 or 2 or 3, wherein R3a and R3b of said suitable amine are independently selected from hydrogen, C1-C4 alkyl or Cs-Ce-C1-C4 cycloalkyl.

15. The process according to claim 1 or 2 or 3, wherein said suitable acid is selected from hydrochloric acid, hydrobromic acid, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, an acidic ion exchange resin or mixtures thereof.

16. The process according to claim 1 or 2 or 3, wherein said suitable base is selected from ammonia, alkali or alkaline earth metal hydroxide or carbonate or bicarbonate, methylamine, dimethylamine, diethylamine, triethylamine, diisopropylamine, diisopropyl ethylamine, pyridine, alkylated and dialkylated pyridines, dimethylaminopyridine, piperidine or mixtures thereof.

17. The process according to claim 16, wherein said alkali or alkaline earth metal is selected from lithium, sodium, potassium, rubidium, cesium, calcium, magnesium, barium or mixtures thereof.

18. The process according to claim 1, wherein the compound of formula (I), R1 is CH3, Br or Cl; R2 is CN, Br or Cl; R3a is H; R3b is methyl or 1cf3 Ñ '-N cyclopropylethyl; R3° is H; R4 is Br or 'N; R5 is Cl; R6 is H or Cl; and Z is N. RPRRCn / LZnZ / q / YIAI 19. The process according to claim 1 or 2 or 3, wherein, in the anthranilic diamide of formula (VI), R1 is CH3, Br or Cl; R2 is CN, Br or Cl; R3a is H; R3b is methyl or 1-cyclopropylethyl; and R3c is H.