PROCESS FOR PREPARING CYANO-SUBSTITUTED ANTHRANILIC DIAMIDES AND THEIR INTERMEDIATES

Description

1 / 22 “PROCESS FOR PREPARING CYANO-SUBSTITUTED ANTHRANILIC DIAMIDES AND INTERMEDIATES THEREOF” Certificate of addition of invention BR 112021016353-0 FIELD OF THE INVENTION:

[0001] The present invention relates to a process for preparing cyano-substituted anthranilic diamides involving the conversion of isatins to isatoic anhydrides. The present invention also relates to a process for preparing cyano-substituted anthranilic amides useful in the process for preparing cyano-substituted anthranilic diamides. BACKGROUND OF THE INVENTION:

[0002] Documents WO2003015518, WO2003015519, WO2004067528, WO2005077934 and WO20100069502 disclose the use of anthranilic diamides to control invertebrate pests such as arthropods.

[0003] Various patent documents, for example, documents WO2004011447, WO2004111030, WO2006062978, WO2008010897 and WO2012103436 discloses processes for preparing anthranilic diamides and suitable intermediates.

[0004] Additionally, document WO2020170092 disclosed the process for the preparation of anthranilic diamides and their intermediates as anthranilic amides. The process disclosed in this invention describes the preparation of anthranilic diamide compounds and halogen-substituted anthranilic amides; however, there is no disclosed method for preparing anthranilic diamide compounds and cyano-substituted anthranilic amides.

[0005] The present invention is further an improvement / modification of the process described in document WO2020170092 for obtaining anthranilic diamide compounds and cyano-substituted anthranilic amides. OBJECTIVES AND SUMMARY OF THE INVENTION:

[0006] One object of the present invention is to provide an industrially suitable and convenient process for the preparation of cyano-substituted anthranilic diamides of Formula I.

[0007] The present invention provides a solution to this objective by providing an improved process that allows the preparation of cyano-substituted anthranilic diamides, overcoming at least one of the shortcomings of the processes described in the prior art. Petition 870250083064, dated 09 / 15 / 2025, p. 11 / 104 2 / 22

[0008] The said objective was achieved according to the present invention by providing an improved process for preparing a compound of Formula I, H, C1-C4 alkyl or C3-C6 CF in which R1 is CH3, Br, or Cl; R2 is CN; R3ae R3bsão independently cycloalkyl-C1-C4 alkyl; R3cé H or C1-C4 alkyl; R4 is Cl, Br, CF3, OCF2H, OCH2CF3AouLs(0)o.2; R5 is F, Cl, or Br; R6 is H, F, or Cl; Z is CR7 or N; and R7 is H, F, Cl, or Br.

[0009] The process according to this invention comprises the step of obtaining a dione of Formula II from an aniline of Formula III and chloral hydrate of Formula IV and convert the dione of Formula II into an isatoic anhydride of Formula V in a single step. The conversion of the dione of Formula II into an isatoic anhydride of Formula V is innovative and inventive since both the oxidation and halogenation reactions are performed in a single step. where R2a is F, Cl, Br or I; R1e is R3csion as defined above in the present Petition 870250083064, dated 09 / 15 / 2025, p. 12 / 104 3 / 22 document.

[0010] The isatoic anhydride of Formula V and an amine of Formula VI are reacted to obtain a compound of Formula VII-A which has been converted into a compound of Formula VII,

[0011] The compound of Formula VII was further reacted with a compound of Formula VIII to obtain the compound of Formula I, R2 VII VIII where R1, R2, R3a, R3b, R3c, R4, R5, R6 and Z are as defined for Formula I; and R8 is OH, Cl, X or O-C1-C4 alkyl.

[0012] In another embodiment, the present invention provides an improved process for the preparation of the compound of Formula (VII) R2 VIIR3c I NHR3a NÍ R3b In what R1 is CH3, Br or Cl; R2 is CN; R3ae R3bsão are independently H, C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R3cé H or C1-C4 alkyl; which includes the following steps: a) oxidize and halogenate the dione of Formula II simultaneously into an anhydride Petition 870250083064, dated 09 / 15 / 2025, p. 13 / 104 4 / 22 isatoic of Formula V using at least one oxidizing reagent and at least one halogenating reagent optionally in the presence of at least one suitable acid; where R2a is F, Cl, Br or I; R1e is R3csion as defined earlier in this document. b) react the compound of Formula V with an amine of Formula VI to obtain a compound of Formula VII-A in the presence of at least one suitable reagent; where R2a is F, Cl, Br or I; R1, R3a, R3b and R3c are defined as previously stated in this document and c) react the compound of Formula VII-A with a cyano source to obtain a compound of Formula VII in the presence of a suitable solvent; VII-A where R2a is F, Cl, Br or I; R1, R2, R3a, R3b and R3c are defined as previously stated in this document. DETAILED DESCRIPTION OF THE INVENTION: GENERAL DEFINITIONS

[0013] The definitions provided herein for the terminology used in this disclosure are for illustrative purposes only and in no way limit the scope of the present invention disclosed in this disclosure.

[0014] As used in this document, the terms “comprises”, “which comprises”, “includes”, “including”, “has”, “which has”, “contains”, “which contains”, “characterized by” or any other variation thereof, are intended to cover Petition 870250083064, dated 09 / 15 / 2025, page 14 / 104 5 / 22 a non-exclusive inclusion, subject to any explicitly stated limitation. For example, a composition, mixture, process or method comprising a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such composition, mixture, process or method.

[0015] The transitional phrase “consisting of” excludes any unspecified element, step, or ingredient. If in the claim, such a phrase would limit the claim to the inclusion of materials other than those mentioned, except for impurities commonly associated with them. When the phrase “consists of” appears in a clause within the body of a claim, rather than immediately following the preamble, it limits only the element established in that clause; other elements are not excluded from the claim as a whole.

[0016] The transitional phrase consisting essentially of is used to define a composition or method that includes materials, steps, features, components, or elements in addition to those literally disclosed, provided that such additional materials, steps, features, components, or elements do not materially affect the basic and innovative feature(s) of the invention claimed. The term “consisting essentially of” serves as an intermediate term between “comprising” and “consisting of”.

[0017] Furthermore, unless expressly stated otherwise, “or” refers to an inclusive “or” and not an exclusive “or”. For example, a condition A or B is satisfied by any of the following: A is 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).

[0018] Furthermore, the indefinite articles "a" and "an," before an element or component of the present invention, are not restrictive with respect to the number of appearances (i.e., occurrences) of the element or component. Therefore, "a" or "an" should be read as including "a" or "at least one," and the singular form of the element or component also includes the plural, unless the number is clearly in the singular.

[0019] 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 through a single bond. Carbon-based radicals may optionally comprise saturated, unsaturated, and aromatic groups, chains, rings and ring systems, and heteroatoms. Although radicals Petition 870250083064, dated 09 / 15 / 2025, p. 15 / 104 6 / 22 carbon-based radicals are not subject to any particular size limit; in the context of the present invention, they typically comprise 1 to 16 carbon atoms and 0 to 3 heteroatoms. Carbon-based radicals selected from C1-C6 alkyl, C1-C6 haloalkyl and phenyl, optionally substituted with 1-3 substituents selected from C1-C3 alkyl, halogen and nitro, are important.

[0020] The meaning of several terms used in the description will now be illustrated.

[0021] The term “alkyl”, used alone or in compound words such as “alkylthio” or “haloalkyl” or -N(alkyl) or alkylcarbonylalkyl or alkylsulfonylamino includes C1 to C24 linear or branched chain alkyl, preferably C1 to C15 alkyl, more preferably C1 to C10 alkyl, most preferably C1 to C6 alkyl.Representative examples of alkyl include methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1dimethylbutyl, 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 l-ethyl-2-methylpropyl or different isomers. If the alkyl group is at the end of a compound substituent, such as in alkylcycloalkyl, the beginning part of the compound substituent, for example, cycloalkyl, may be identically or differently and independently mono- or polysubstituted by alkyl.The same also applies to compound substituents in which other radicals, for example, alkenyl, alkynyl, hydroxyl, halogen, carbonyl, carbonyloxy and the like, are at the end.

[0022] The term “cycloalkyl” means alkyl closed to form a ring. Representative examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. This definition also applies to cycloalkyl as part of a composite substituent, for example, cycloalkylalkyl etc., unless specifically defined otherwise.

[0023] Consequently, in one embodiment, the present invention provides a method for preparing the compound of Formula (VII) R1R3c THE VII Petition 870250083064, dated 09 / 15 / 2025, p. 16 / 104 7 / 22 in which R1 is CH3, Br or Cl; R2 is CN; R3ae R3bsão are independently H, C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R3cé H or C1-C4 alkyl; which includes the following steps: a) oxidize and halogenate the dione of Formula II simultaneously in an isatoic anhydride of Formula V using at least one oxidizing reagent and at least one halogenating reagent, optionally in the presence of at least one suitable acid; where R2a is F, Cl, Br or I; R1e is R3csion as defined earlier in this document. b) react the compound of Formula V with an amine of Formula VI to obtain a compound of Formula VII-A in the presence of at least one suitable reagent; where R2a is F, Cl, Br or I; R1, R3a, R3b and R3c are defined as previously stated in this document and c) react the compound of Formula VII-A with a cyano source to obtain a compound of Formula VII in the presence of a suitable solvent; where R2a is F, Cl, Br or I; R1, R2, R3a, R3b and R3c are defined as previously stated in this document.

[0024] In another embodiment, the present invention relates to a process for Petition 870250083064, dated 09 / 15 / 2025, p. 17 / 104 8 / 22 prepare a compound of Formula I, in what R1 is CH3, Br or Cl; R2 is CN; R3ae R3bsão are independently H, C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R3cé H or C1-C4 alkyl; cf3o R4 is Cl, Br, CF3, OCF2H, OCH2CF3 or or; R5 is F, Cl, or Br; R6 is H, F, or Cl; Z is CR7 or N; and R7 is H, F, Cl, or Br.

[0025] The process of the present invention is described later in this document.

[0026] Aniline of Formula III and chloral hydrate of Formula IV were reacted to obtain the dione of Formula II. where R1e R3csion as defined in the present document above.

[0027] In one embodiment, the compound of Formula III and chloral hydrate of Formula IV are reacted in the presence of one or more suitable reagents including, but not limited to, hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, nitric acid and sodium sulfate in one or more solvent(s) at a temperature in the range of 25 °C to 100 °C, followed by stirring with mineral acid including, but not limited to, sulfuric acid, hydrochloric acid and nitric acid at 0 °C to 45 °C to obtain the dione of Formula II. Petition 870250083064, dated 09 / 15 / 2025, p. 18 / 104 9 / 22

[0028] In another embodiment, the oxime of Formula IIIa is formed by the reaction of the compound of Formula III and chloral hydrate of Formula IV or hydroxylamine in the presence of one or more suitable reagents including, but not limited to, hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, nitric acid and sodium sulfate and one or more solvents at a temperature in the range of 15 °C to 150 °C. W, III IV where R1 and R3 are as defined in the present document above.

[0029] The solvent useful in this step includes, but is not limited to, aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, dodecane and the like; alicyclic hydrocarbons such as cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane and the like; aromatic hydrocarbons such as toluene, xylene, mesitylene, benzene and the like; ethers such as diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, methyl alcohol, ethyl alcohol, acetone, dioxane, monoglyceride, diglylene, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane and the like; halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane and the like; ethers, polar aprotic solvents such as N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone, hexamethylphosphoramidan, 1,3-dimethyl-2-imidazolidinone and the like; and water.

[0030] The oxime of Formula IIIa is then converted into the compound of Formula II by the use of mineral acid including, but not limited to, sulfuric acid, hydrochloric acid and nitric acid and stirring within a temperature in the range of 0 °C to 150 °C.

[0031] The dione of Formula II is converted into an isatoic anhydride of Formula V using suitable halogenation reagents, one or more suitable oxidation reagents, or one or more suitable solvents at a temperature in the range of 0°C to 250°C. Petition 870250083064, dated 09 / 15 / 2025, page 19 / 104 10 / 22 where R2a is F, Cl, Br or I; R1 and R3c are as defined in the present document above.

[0032] The halogenating reagent useful for converting the dione of Formula II into the isatoic anhydride of Formula V includes, but is not limited to, HX, NaX, KX, CuX2, MgX2, CsX, ZnX2, SOCl2, SO2Cl2, COCl2, X2, C(=O)(OCl3)2, t-BuOCl, NaOCl, Chloramine-T, N-halosuccinamides, POX3, PX3, PX5 or metal halides; wherein X is Cl, Br, I or F.

[0033] Useful oxidation reagents for converting the dione of Formula II into the isatoic anhydride of Formula V include, but are not limited to, hydrogen peroxide, t-butyl hydroperoxide, tungstic peroxide, m-chloroperbenzoic acid, benzoyl peroxide, hypohalous acid, ammonium ceric nitrate, ammonium hypoceric nitrate, oxone, periodic acid, hydrogen peroxide urea adduct, sodium perborate, pyridinium chlorochromate, and dimethyl sulfoxide.

[0034] The acidic reagents that are optionally used to convert the dione of Formula II into the isatoic anhydride of Formula V include, but are not limited to, formic acid, acetic acid, triflic acid, benzoic acid, mchlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, galeic acid, tartaric acid, ascorbic acid, hydrochloric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, and perchloric acid;

[0035] The solvent useful for converting the dione of Formula II into the isatoic anhydride of Formula V includes, but is not limited to, an organic acid selected from the group consisting of formic acid, acetic acid, triflic acid, butyric acid, propionic acid, carbonic acid, glycolic acid, and trifluoroacetic acid.

[0036] Alternatively, solvents useful for converting the dione of Formula II into the isatoic anhydride of Formula V include, but are not limited to, a mixture of said organic acid(s) with one or more solvent(s) selected from the group comprising aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, dodecane and the like; alicyclic hydrocarbons such as cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, Petition 870250083064, dated 09 / 15 / 2025, page 20 / 104 11 / 22 cyclooctane and similar substances; aromatic hydrocarbons such as toluene, xylene, mesitylene, benzene and similar substances; ethers such as diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, methyl alcohol, ethyl alcohol, acetone, dioxane, monoglyceride, diglylene, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane and similar substances; halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane and similar substances; Polar aprotic solvents such as N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramidan, 1,3-dimethyl-2-imidazolidinone, acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid and the like; and water.

[0037] In one embodiment, the conversion step of the dione of Formula II into the isatoic anhydride of Formula V is performed by mixing i) a mixture of the halogenation reagent and the oxidation reagent, and ii) a mixture of the dione of Formula II and the solvent, at a temperature in the range of 10 to 50 °C and then by heating to a temperature in the range of 15-150 °C.

[0038] In another embodiment, the conversion step of the dione of Formula II into the isatoic acid of Formula V is performed by mixing i) the halogenation reagent and ii) the oxidation reagent separately in sequence with iii) a mixture of the dione of Formula II and the solvent, at a temperature in the range of 10 to 50 °C, followed by heating to a temperature in the range of 15-150 °C.

[0039] In one embodiment of the present invention, step (a) is performed in acetic acid as solvent in a ratio of 2 to 10 w / w volumes relative to the compound of formula (II).

[0040] In one embodiment of the present invention, halogenation and oxidation in step (a) are carried out in the presence of HX / H2O2 reagent in the ratio of 1 to 10 molar equivalents relative to the compound of formula (II).

[0041] In one embodiment of the present invention, the sulfuric acid used in step (a) is in the proportion of 0.01 to 0.5 molar equivalents relative to the compound of formula (II); preferably, 0.01 to 0.1 molar equivalents.

[0042] In the next step, the isatoic anhydride of Formula V and an amine of Formula VI are reacted to obtain a compound of Formula VII-A, Petition 870250083064, dated 09 / 15 / 2025, page 21 / 104 12 / 22 where R2a is F, Cl, Br or I; R1, R2, R3a, R3b and R3c are as defined previously in this document.

[0043] The amine of Formula VI can be used in aqueous form or a gaseous form. For example, when R3a is methyl, then methylamine is used for the preparation of the compound of Formula VII, where R3a is methyl; in this case, methylamine can be used in gaseous form or can be used as a solution in water or one or more solvent(s).

[0044] The solvents that are useful for this reaction are preferably selected from the group comprising aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, dodecane and the like; alicyclic hydrocarbons such as cycloalkanes: cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane and the like; aromatic hydrocarbons such as toluene, xylene, mesitylene, benzene and the like; ethers such as diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, methyl alcohol, ethyl alcohol, acetone, dioxane, monoglyceride, diglylene, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane and the like; Halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane and similar substances;ethers, polar aprotic solvents such as N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramidan, 1,3-dimethyl-2-imidazolidinone and the like; and water.

[0045] The conversion of the isatoic anhydride of Formula V and the amine of Formula VI may additionally require the presence of a suitable reagent selected from the group consisting of formic acid, acetic acid, triflic acid, benzoic acid, m-chlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, tartaric acid, ascorbic acid, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, boronic acids, amberlysts, aluminum chloride, zinc chloride, trifluoroborone ether, zinc oxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, pyridine, N-methyl-2-pyrrolidone and N,N-dimethylmethanamide;

[0046] The temperature conditions employed for the conversion of the isatoic anhydride of Formula V and the amine of Formula VI are in the range of 0 °C to 150 °C, depending on the solvent used and the amine reagent employed.

[0047] In one embodiment, the Formula V compound is isolated.

[0048] In another embodiment, the Formula V compound is not isolated. Petition 870250083064, dated 09 / 15 / 2025, p. 22 / 104 13 / 22

[0049] In one embodiment, the isatoic anhydride of Formula V, wherein R2a is F, Cl, Br, or I, can be converted into a compound of Formula VII, wherein R2 is CN.

[0050] In another embodiment, the compound of formula VII-A is converted into a compound of formula VII using cyano sources, in the presence of a suitable solvent and optionally in the presence of a ligand and catalyst. R1R3cR1R3c VII-A VII where, R2a is F, Cl, Br or I; R1, R2, R3a, R3b and R3csion as defined previously in this document.

[0051] In one embodiment, the cyanation reactions or the cyanation mentioned in step-c of the present invention is carried out in the presence of metal cyanides as a source of CN.

[0052] In one embodiment, to obtain the compound of formula VII from the compound of formula VIIA, the source of CN- ions in carrying out the cyanation or cyanation reactions mentioned in step-c of the present invention is selected from metallic cyanide, particularly sodium cyanide (NaCN), potassium cyanide (KCN), copper(I) cyanide (CuCN), zinc(II) cyanide (Zn(CN)2), sodium ferrocyanide (Na4Fe(CN)e), potassium hexacyanoferrate(III) (K3[Fe(CN)6]), potassium hexacyanoferrate(II) (K4[Fe(CN)e]).

[0053] In one embodiment, to obtain the compound of formula VII from the compound of formula VIIA, the source of CN- ions in carrying out the cyanation or cyanation reactions mentioned in step-c of the present invention, which is selected from metal cyanide, is potassium hexacyanoferrate (II) (K4[Fe(CN)e]).

[0054] In one embodiment, the cyanation or cyanation reactions mentioned in step-c of the present invention are carried out in the presence of a ligand and / or catalyst.

[0055] The ligand used to carry out the cyanation or cyanation reactions mentioned in step-c of the present invention is selected from 1,2-dimethylethylenediamine (DMEDA), imidazole, 1-butyl-IH-imidazole, 2-picoline, 3-picoline, 2,6-lutidine, 1-methylpyrolidine or pyrolidine.

[0056] The ligand used in carrying out the cyanation or cyanation reactions mentioned in step-c of the present invention is imidazole.

[0057] The catalyst used in carrying out the cyanation or cyanation reactions mentioned in step c of the present invention is selected from salts of Petition 870250083064, dated 09 / 15 / 2025, page 23 / 104 14 / 22 Copper as copper(I) iodide (CuI), copper(I) chloride, copper(I) bromide, copper acetate.

[0058] The catalyst used in carrying out the cyanation or cyanation reactions mentioned in step-c of the present invention is selected from copper salts, preferably copper(I) iodide (CuI).

[0059] The temperature at which the cyanation or cyanation steps mentioned in step-c are performed is in the range of 30 °C to 200 °C

[0060] The solvents useful in carrying out the cyanation or cyanation reaction mentioned in step c of the present invention are selected from N,N-dimethylmethanamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, 1,3-dimethyl3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramidan, or 1,3-dimethyl-2imidazolidinone; more preferably, N,N-dimethylformamide, N-methyl-2-pyrrolidone; preferably, amide solvents selected from N,N-dimethylmethanamide, N,N-dimethylacetamide or N-methyl-2-pyrrolidone.

[0061] The solvents useful in carrying out the cyanation or cyanation reaction mentioned in step c of the present invention are preferably selected from N,N-dimethylformamide, N,N-dimethylacetamide or N-methyl-2-pyrrolidone.

[0062] In one embodiment of the present invention, copper(I) iodide used in step (c) is in the proportion of 0.08 to 0.01 molar equivalents relative to the compound of formula (VII-A); preferably, 0.05 to 0.03 molar equivalents.

[0063] In one embodiment of the present invention, the cyano K4Fe(CN)6 source used in step (c) is in the proportion of 1 to 0.4 molar equivalents relative to the compound of formula (VII-A); preferably, 0.8 to 0.6 molar equivalents.

[0064] In one embodiment of the present invention, the imidazole ligand used in step (c) is in the proportion of 0.8 to 0.2 molar equivalents relative to the compound of formula (VII-A); preferably, 0.6 to 0.3 molar equivalents.

[0065] In one embodiment of the present invention, the amide solvent used in step (c) is in the ratio of 6 w / w 1 w / w to the compound of formula (VII-A).

[0066] In one embodiment, the purity of the compound of formula (VII) is greater than 98%.

[0067] Finally, the compound of Formula VII and a compound of Formula VIII are reacted to obtain the compound of Formula I, Petition 870250083064, dated 09 / 15 / 2025, p. 24 / 104 15 / 22 VII where R1, R2, R3a, R3b, R3c, R4, R5, R6 and Z are as defined previously in this document; R8 is OH, Cl or O-C1-C4 alkyl.

[0068] The compound of Formula VIII can be obtained by one of the processes disclosed in documents WO2003015518, WO20030155519, WO2011157664 and WO2013030100,

[0069] Any or all of the process steps of the present invention can be performed in continuous, semi-continuous, flow or batch mode. In particular, the process steps of the present invention are performed in semi-continuous mode.

[0070] Any or all of the process steps can be performed at a pressure in the range of 0.5 kg / cm2 to 250 kg / cm2.

[0071] Anyone skilled in the art knows the best way to prepare reaction mixtures after the reactions have ended. In one embodiment, the preparation is usually carried out by isolating the product by filtration, and optionally washing with a solvent, and optionally drying the product if required.

[0072] The preparation / isolation of the reaction product can also be carried out by a technique that includes, but is not limited to, decantation, centrifugation, evaporation, ultrafiltration, liquid-liquid extraction, distillation, recrystallization, chromatography and the like.

[0073] The method steps according to the invention are generally performed under atmospheric pressure. Alternatively, however, it is also possible to work under reduced pressure or under pressure.

[0074] Without further explanation, it is believed that anyone skilled in the art who is using the preceding description can utilize the present invention to its fullest extent. The following examples should therefore be interpreted as merely illustrative and not limiting the disclosure in any form.

[0075] The present invention will now be described in the light of the following examples. Petition 870250083064, dated 09 / 15 / 2025, p. 25 / 104 16 / 22 non-limiting. Example 1: Step A: Preparation of 2-(hydroxyimino)-N-(o-tolyl)acetamide

[0076] To a solution of o-toluidine (75 g, 700 mmol) in water (170 ml), hydrochloric acid (73 g, 700 mmol, 35% w / w) was slowly added, followed by the addition of a solution of anhydrous sodium sulfate (636 g, 4478 mmol) in water (800 ml). The resulting reaction mixture was heated to 55 °C. Then, an aqueous solution of hydroxylamine hydrochloride (73 g, 1050 mmol) in water (280 ml) was slowly added, followed by the addition of chloral hydrate (125 g, 757 mmol) in water (270 ml). The reaction mixture was maintained at 55 °C for 12 h. After completion of the reaction, the reaction mixture was cooled to 20 °C and stirred for 1 h. The solid product obtained was filtered, washed with water (100 ml) and dried to obtain 2-(hydroxyimino)-N-(o-tolyl)acetamide (95 g, 531 mmol, Yield: 76%).

[0077] 1H-NMR (400 MHz, DMSO-d6) δ 12.16 (s, 1H), 9.47 (bs, 1H), 7.66 (s, 1H), 7.45-7.47 (d, J = 7.8 Hz, 1H), 7.19-7.24 (dd, J = 7.4 Hz & 0.6 Hz, 1H), 7.14-7.18 (td, J = 7.6 Hz & 1.6 Hz, 1H), 7.08-7.13 (td, J = 7.4 Hz & 1.3 Hz, 1H), 2.22 (s, 3H); MS: m / z = 179.05 [M+H]. Step B-1: Preparation of 7-methylindoline-2,3-dione

[0078] 2-(Hydroxyimino)-N-(o-tolyl)acetamide (92 g, 485 mmol) was added in batch to a sulfuric acid solution (333 g, 3397 mmol) at 0-5 °C. The temperature was allowed to slowly rise to 30 °C, and the reaction mixture was stirred for 12 h. After completion of the reaction, the reaction mixture was slowly poured into water (1800 ml). The precipitated solid product was filtered, washed with water (200 ml), and dried to obtain 7-methylindoline-2,3-dione (71.5 g, 485 mmol, Yield: 91%).

[0079] 1H-NMR (400 MHz, DMSO-d6) δ 11.08 (s, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 2.17 (s, 3H); MS: m / z = 162.00 [M+H]. Step B-2: Preparation of 7-methylindoline-2,3-dione

[0080] 2-(Hydroxyimino)-N-(o-tolyl)acetamide (10 g, 15.8 mmol) was added in batch to a solution of sulfuric acid (36.2 g, 369 mmol) and 1,2-dichloroethane (50 ml) at 0-5 °C. The temperature was allowed to rise to 30 °C and the reaction mixture was stirred for 12 h. After the reaction was complete, the reaction mixture was slowly poured into water (190 ml). The dichloroethane was removed under reduced pressure and the remaining suspended solid product was filtered, washed with water (20 ml) and dried to obtain 7-methylindoline-2,3-dione (8.1 g, 50 mmol). Yield: Petition 870250083064, dated 09 / 15 / 2025, page 26 / 104 17 / 22 95%). Step C-1: Preparation of 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione

[0081] 7-Methylindoline-2,3-dione (50 g, 261 mmol) and acetic acid (421 g) were mixed at 25 °C to obtain a suspension. To this suspension, hydrogen peroxide (163 g, 1437 mmol, 30% w / w) was added slowly at 25 °C for 15 min under stirring, followed by the addition of concentrated hydrochloric acid (82.0 g, 653 mmol, 29% w / w) at a temperature between 30 and 40 °C for 45 min. The reaction mixture was stirred for 3 h at 40 °C. The reaction mass was then heated to 70 °C for 4 h. After the reaction was complete, the reaction mass was cooled to 25 °C and then slowly poured over a mixture of crushed ice and water (415 g) under stirring. The solid obtained by this procedure was filtered, washed with cold water (100 ml) and dried under reduced pressure to obtain crude 6-chloro-8-methyl-2Hbenzo[d][1,3]oxazine-2,4(1H)-dione (46 g, 261 mmol, Yield: 83%). Step C-2: Preparation of 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione

[0082] 7-Methylindoline-2,3-dione (20 g, 116 mmol) and acetic acid (187 g, 3127 mmol) were mixed at 25 °C to obtain a suspension. To this suspension, hydrogen peroxide (Batch 1) (18 g, 232 mmol) was added slowly over 5 min at the same temperature, followed by the addition of hydrochloric acid (51.0 g, 406 mmol) over 30 min at 15 °C. The resulting reaction mass was stirred for 2 h at 25 °C. Then, hydrogen peroxide (Batch 2) (27 g, 348 mmol) was added slowly over 30 min at 15 °C under stirring. The reaction mixture was heated to 60 °C and stirred for 6 h. Hydrogen peroxide (Batch 3) (12 g, 174 mmol) was added slowly at 20 °C with stirring. The reaction mixture was heated to 60 °C and stirred further for 2 h. The reaction was slowly quenched by pouring it into cooled water (930 g) at 0 °C. The resulting mixture was stirred for 1 h at 0 °C.The solid obtained was filtered, washed with chilled water and dried under reduced pressure to obtain 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione (15.4 g, 72.8 mmol, Yield: 63%).

[0083] 1H-NMR (400 MHz, DMSO-d6) δ 11.17 (s, 1H), 7.73 (dd, J = 2.4 Hz & 0.5 Hz, 1H), 7.69 (dd, J = 2.4 Hz & 0.7 Hz, 1H), 2.34 (s, 3H). MS: m / z = 209.90 [MH]. Step C-3: Preparation of 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione

[0084] 7-Methylindoline-2,3-dione (50 g, 298 mmol) and acetic acid (483 g, 8047 mmol) were mixed at 5 °C to obtain a suspension. Hydrogen peroxide (Batch 1) (69 g, 894 mmol) was added under stirring to this suspension at 5 °C for 15 min. Then, hydrochloric acid (Batch 1) (56 g, 447 mmol) was added slowly under stirring at 5 °C for 60 min. The resulting reaction mass was stirred. Petition 870250083064, dated 09 / 15 / 2025, page 27 / 104 18 / 22 additionally for 2.5 h at 10 °C, then allowed to warm to 20 °C and stirred further for 23 h. Hydrogen peroxide (Batch 2) (26 g, 313 mmol) was added at 10 °C for 15 min under stirring, and then HCl (Batch 2) (18 g, 158 mmol) was added under stirring slowly for 30 min at 10 °C. The reaction mass was stirred at 40 °C for 3 h. The resulting solid was washed with water (600 ml) and dried under reduced pressure to obtain 6-chloro-8-methyl-2Hbenzo[d][1,3]oxazine-2,4(1H)-dione (52.70 g, 298 mmol, Yield: 84%). Step C-4: Preparation of 6-bromo-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)dione:

[0085] To a suspension of 7-methylindoline-2,3-dione (10 g, 60.0 mmol) and acetic acid (100 g), hydrogen peroxide (27 g, 360 mmol) was added at 25-30 °C. To this reaction mixture, hydrobromic acid (11 g, 57.1 mmol) was added at a temperature between 15-25 °C for 1 h. After stirring for 2 h at 25-30 °C, sulfuric acid (0.3 g, 3.0 mmol) was added and the reaction mass was heated to 45-50 °C and stirred further for 8 h. The temperature was slowly raised to 70-75 °C and stirred further for 2 h. After the reaction was complete, the reaction mixture was cooled to 25 °C and slowly poured over a mixture of crushed ice and water (500 g) under constant stirring at 0-5 °C. The resulting solid was filtered, washed with cold water, and dried under reduced pressure to obtain crude 6-bromo-8-methyl-2Hbenzo[d][1,3]oxazine-2,4(1H)-dione (11.5 g, 45 mmol, Yield: 75%).

[0086] 1H-NMR (400 MHz, DMSO-d6) δ 11.16 (s, 1H), 7.83 (d, J = 2.4 Hz, 1H), 7.78 (d, J = 2.4 Hz, 1H), 2.31 (s, 3H) LCMS: m / z = 254 [M-2H]. Step D-1: Preparation of 2-amino-5-chloro-N,3-dimethylbenzamide

[0087] A suspension of 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)dione (17 g, 80 mmol), acetic acid (10 g, 160 mmol) and ethyl acetate (200 ml) was cooled under stirring to 0 °C. Methylamine gas was bubbled through this stirred suspension at 0 °C for 15 min (pH = 9 to 10). The resulting reaction mixture was then allowed to warm to 25 °C and stirred further for 3 h. After completion of the reaction, the reaction mixture was poured into water (200 g) and extracted with ethyl acetate (200 g). The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide (12.0 g, 60.4 mmol, Yield: 75%).

[0088] 1H-NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 4.2 Hz, 1H), 7.37-7.38 (d, J = 2.4 Hz, 1H), 7.10-7.12 (d, J = 2.4 Hz, 1H), 6.35 (s, 2H), 2.72 (d, J = 4.4 Hz, 3H), Petition 870250083064, dated 09 / 15 / 2025, p. 28 / 104 19 / 22 2.08 (s, 3H). MS: m / z = 199.00 [M+H]. Step D-2: Preparation of 2-amino-5-chloro-N,3-dimethylbenzamide

[0089] A mixture of 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione (0.5 g, 2.4 mmol), methylamine hydrochloride (0.32 g, 4.7 mmol) and potassium carbonate (0.33 g, 2.4 mmol) in ethyl alcohol (10 ml) was stirred for 0.5 h at 25 °C, and then heated to 80 °C for 5 h. After the reaction was complete, the reaction mixture was poured into ice-water (50 ml). The precipitate obtained was filtered and washed with water (5 ml). The mother liquor was extracted with dichloromethane (50 ml). The combined dichloromethane layers were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a solid. Both solids were combined to obtain crude 2-amino-5-chloro-N,3-dimethylbenzamide (0.3 g, 1.5 mmol, Yield: 64%). Step D-3: Preparation of 2-amino-5-chloro-N,3-dimethylbenzamide

[0090] A mixture of 6-chloro-8-methyl-2H-benzo[d][1,3]oxazine-2,4(1H)-dione (0.5 g, 2.4 mmol), methylamine hydrochloride (0.32 g, 4.7 mmol) and pyridine (0.4 ml, 4.7 mmol) in ethyl alcohol (10 ml) was heated at 80 °C for 2 h. After the reaction was complete, the reaction mixture was diluted with water (50 ml) and extracted with ethyl acetate (50 ml). The ethyl acetate layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a crude solid. The crude solid was triturated with n-hexane (50 ml) to obtain pure 2-amino-5-chloro-N,3-dimethylbenzamide (0.3 g, 1.4 mmol, Yield: 60%). Example 2: Preparation of Brisatoic anhydride

[0091] To a solution of isatin (111 g, 1 eq., 623 mmol) in acetic acid (1035 g), 50% aqueous hydrogen peroxide (257 g, 6 eq., 3741 mmol) was added dropwise over a period of 15–20 min at room temperature. The reaction mixture was cooled to 12–15 °C, followed by the addition of 47% aqueous hydrobromic acid (102 g, 0.95 eq., 592 mmol) over a period of 30 min. The resulting mixture was heated to room temperature and allowed to stir for 2 h. After completion of the reaction, sulfuric acid (3.06 g, 0.05 e., 31.2 mmol) was added to the reaction mixture and further heated to 50–5 °C for 30 min. The reaction temperature was then increased to 65±5 °C and stirred further for 5–6 h at the same temperature. After the reaction was complete, the reaction mixture was Petition 870250083064, dated 09 / 15 / 2025, p. 29 / 104 20 / 22 gradually cooled to room temperature and poured into ice-cold water (1000 g). The precipitate obtained was filtered and dried to obtain isatoic bromine anhydride as an amorphous orange solid (148.9 g; Yield: 76.87%)

[0092] 1H NMR (DMSO-d6) δ: 11.16 (br s, 1H), 7.82 (d, J = 1.6 Hz, 1H), 7.77 (d, J = 1.6 Hz, 1H), 2.39 (s, 3H).

[0093] 13C-NMR (DMSO-d6) δ: 158.9, 146.9, 139.7, 139.1, 128.6, 127.5, 114.3, 114.1, 112.3, 16.8 Example 3: Preparation of 2-amino-5-bromo-N,3-dimethylbenzamide

[0094] To a stirred solution of Br-isatoic anhydride (1.0 eq., 195 mmol, 50 g) in ethyl acetate (450 g) and acetic acid (1.5 eq., 293 mmol, 17.5 g), methylamine (1.5 eq., 293 mmol, 23.33 g, 39% in aqueous solution) was slowly added at 25±5 °C for a period of 15-20 min. The resulting reaction mixture was continued to be stirred for 4-5 h at room temperature. After completion of the reaction, an aqueous solution of sodium bicarbonate (13.7 g in 500 g of water) was added to the reaction mixture at room temperature and heated to 45±5 °C under stirring for 1 h. The reaction mixture was cooled to 30±5 °C, and the organic layer was separated. The aqueous layer was washed with EtOAc (2 x 45 g). The combined organic layers were washed with saturated (25%) brine solution (45 g), dried with anhydrous sodium sulfate, concentrated under reduced pressure to yield the crude product (46 g, Yield: 98.57%).

[0095] 1H NMR (DMSO-d6, 400 MHz) δ: 8.32 (br d, 1H), 7.49 (d, 1H), 7.22 (d, 1H), 6.35 (br s, 2H), 2.70 (d, 3H), 2.08 (s, 3H);

[0096] 13C NMR (DMSO-d6, 100 MHz) δ: 168.4, 146.8, 134.2, 127.7, 125.9, 6.1, 105.0, 26.0, 17.2; Example 4: Synthesis of 2-amino-5-cyano-N,3-dimethylbenzamide Condition 1:

[0097] A mixture of n-butanol (100 ml) and N-methyl-2-pyrrolidone (NMP, 25 ml), 2-amino-5-bromo-N,3-dimethylbenzamide (25 g, 102 mmol, 1 equivalent), potassium iodide (0.85 g, 5.1 mmol, 0.05 equivalent), copper(I) iodide (0.98 g, 5.1 mmol, Petition 870250083064, dated 09 / 15 / 2025, page 30 / 104 21 / 22 Potassium ferrocyanide trihydrate ((K4Fe(CN)6.3H2O), 17.39 g, 41.1 mmol, 0.4 equivalent), and technical grade α-dimethylethylenediamine ((DMEDA), 4.53 g, 51 mmol, 0.5 equivalent) were added. The reaction mixture was stirred under a nitrogen atmosphere at 120 °C for 20 h. After the reaction was complete, the reaction mixture was cooled to 45 °C. The resulting solid was filtered, washed with n-butanol, and dried to obtain 14.60 g of 2-amino-5-cyano-N,3-dimethylbenzamide.

[0098] 1H-NMR (400 MHz, DMSO-d6) δ 8.41 (bs, 1H), 7.80 (d, J=1.6 Hz, 1H), 7.42 (d, J=1.6 Hz, 1H), 7.16 (bs, 1H), 2.72 (d, J= 4.8 Hz, 3H), 2.08 (s, 3H) MS: m / z 190.3 [M-1]+ Condition 2:

[0099] A mixture of N-methyl-2-pyrrolidone (NMP, 77 g), 2-amino-5-bromoN,3-dimethylbenzamide (50 g, assay of 98.3, 204 mmol, 1 equivalent), potassium ferrocyanide trihydrate ((K4Fe(CN)6.3H2O), 25.9 g, 60.7 mmol, 0.3 equivalent), copper(I) iodide (1.556 g, 8.08 mmol, 0.04 eq) and imidazole (5.56 g, 81 mmol, 0.4 equivalent) were added. The reaction mixture was stirred under a nitrogen atmosphere at 160-165 °C for 30 h. After the reaction was complete, the mixture was prepared to produce 2-amino-5-cyano-N,3-dimethylbenzamide (37.7 g, 98.56% yield) as a light brown solid.

[0100] 1H-NMR (400 MHz, DMSO-d6) δ 8.41 (bs, 1H), 7.80 (d, J=1.6 Hz, 1H), 7.42 (d, J=1.6 Hz, 1H), 7.16 (bs, 1H), 2.72 (d, J= 4.8 Hz, 3H), 2.08 (s, 3H) MS: m / z 190.3 [M-1]+ Condition 3:

[0101] To a mixture of N,N-Dimethylacetamide (DMAc, 30 ml), 2-amino-5-bromo-N,3-dimethylbenzamide (30 g, 123 mmol, 1 equivalent), potassium ferrocyanide trihydrate ((K4Fe(CN)6.3H2O), 31.27 g, 74 mmol, 0.6 equivalent), copper(I) iodide (2.35 g, 12.34 mmol, 0.1 eq), and imidazole (4.2 g, 61.7 mmol, 0.5 equivalent) were added. The reaction mixture was stirred under a nitrogen atmosphere at 145-150 °C for 43 h. After completion of the reaction, the mixture was prepared to produce 2-amino-5-cyano-N,3-dimethylbenzamide (19.3 g, 82.65% yield) as a light brown solid.

[0102] 1H-NMR (400 MHz, DMSO-d6) δ 8.41 (bs, 1H), 7.80 (d, J=1.6 Hz, 1H), 7.42 (d, J=1.6 Hz, 1H), 7.16 (bs, 1H), 2.72 (d, J= 4.8 Hz, 3H), 2.08 (s, 3H) MS: m / z 190.3 [M-1]+ Example 5: Preparation of 1-(3-chloropyridin-2-yl)-N-(4-cyano-2-methyl-6(methylcarbamoyl)phenyl)-3-((5-(trifluoromethyl)-2H-tetrazol-2-yl)methyl)-1H-pyrazol-5-carboxamide Petition 870250083064, dated 09 / 15 / 2025, page 31 / 104 22 / 22

[0103] The compound above is prepared according to the procedure mentioned in example 1 and step 5 of document WO2019224678 according to the following scheme: n=n MeSO2Cl, Py °C, 6 h Petition 870250083064, dated 09 / 15 / 2025, page 32 / 104

Claims

1 / 8 CLAIMS 1. Process for preparing a compound of Formula VII, characterized in that R1 is CH3, Br or Cl; R2 is CN; R3a and R3b are independently H, C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; and R3c is independently H or C1-C4 alkyl; comprising the steps of a) oxidizing and halogenating the dione of Formula II simultaneously in isatoic anhydride of Formula V using at least one oxidizing reagent and at least one halogenating reagent optionally in the presence of at least one suitable acid; wherein, R2a is F, Cl, Br or I; R1 and R3c are as defined previously in this document, b) reacting the compound of Formula V with an amine of Formula VI to obtain a compound of Formula VIIA in the presence of at least one suitable reagent; wherein, R2a is F, Cl, Br or I; R1, R3a, R3b and R3c are as defined previously in this document and Petition 870250083064, dated 09 / 15 / 2025, page 1.33 / 104 2 / 8 c) react the compound of Formula VIIA with a cyano source to obtain a compound of Formula VII in the presence of an amide solvent; VIIA vii wherein, R2a is F, Cl, Br or I; R1, R2, R3a, R3b and R3c are as defined previously in this document.

2. Process according to claim 1, characterized in that step c is carried out in the presence of a binder and / or catalyst.

3. Process according to claim 1, characterized in that the cyanide source in step c is metal cyanides that are selected from sodium cyanide (NaCN), potassium cyanide (KCN), copper(I) cyanide (CuCN), zinc(II) cyanide (Zn(CN)2), sodium ferrocyanide (Na4Fe(CN)6), potassium hexacyanoferrate (III) (K3[Fe(CN)6]) or potassium hexacyanoferrate (II) (K4[Fe(CN)6]).

4. Process according to claim 3, characterized in that the metal cyanides are potassium hexacyanoferrate (II) (K4[Fe(CN)6]).

5. Process according to claim 2, characterized in that the ligand is selected from 1,2-dimethylethylenediamine (DMEDA), imidazole, 1-butyl-1H-imidazole, 2-picoline, 3-picoline, 2,6-lutidine, 1-methylpyrolidine or pyrolidine.

6. Process according to claim 2, characterized in that the binder is imidazole.

7. Process according to claim 2, characterized in that the catalyst is a copper salt and selected from copper(I) iodide (CuI), copper(I) chloride (CuCl), copper(I) bromide (CuBr).

8. Process according to claim 7, characterized in that the catalyst is a copper salt that is copper(I) iodide (CuI).

9. Process according to claim 1, characterized in that step c is carried out in the presence of an amide solvent selected from N,N-dimethylformamide, N,N-dimethylacetamide or N-methyl-2-pyrrolidone.

10. Process for preparing anthranilic diamide of Formula I, Petition 870250083064, dated 09 / 15 / 2025, p. 34 / 104 3 / 8 characterized in that R1 is CH3, Br or Cl; R2 is CN; R3a and R3b are independently H, C1-C4 alkyl or C3-C6 cycloalkyl-C1-C4 alkyl; R3c is H or C1-C4 alkyl; R4 is Cl, Br, CF3, OCF2H, OCH2CF3 or O^(0)O-2; R5 is F, Cl or Br; R6 is H, F or Cl; Z is CR7 or N; and R7 is H, F, Cl or Br; wherein the said process comprises the steps of: a) oxidizing and halogenating the dione of Formula II simultaneously in an isatoic anhydride of Formula V using at least one oxidizing reagent and at least one halogenating reagent optionally in the presence of at least one suitable acid; wherein, R1, R2 and R3c are as defined previously in this document, b) reacting the compound of Formula V with an amine of Formula VI to obtain a compound of Formula VII in the presence of at least one suitable reagent; Petition 870250083064, dated 15 / 09 / 2025, p.35 / 104 4 / 8 where, R1, R2, R3a, R3b and R3c are as defined previously in this document; e) react the compound of Formula VIIA with a cyano source to obtain a compound of Formula VII in the presence of a suitable solvent, optionally in the presence of a ligand and catalyst; oo VIIA VII where, R2a is F, Cl, Br or I; R1, R2, R3a, R3b and R3c are as defined previously in this document; d) react the compound of Formula VII and a compound of Formula VIII to the compound of Formula I in the presence of at least one suitable reagent; p3b p3a VII VIII I where, R8 is OH, Cl, X or O-C1-C4 alkyl; R1, R2, R3a, R3b, R3c, R4, R5, R6 and Z are as defined previously in this document and where the compound of Formula V may or may not be isolated.

11. Process according to claim 1, characterized in that the process step (a) is carried out i) using a suitable halogenation reagent selected from the group consisting of HX, NaX, KX, CuX2, MgX2, CsX, ZnX2, SOCl2, SO2Cl2, COCl2, X2, C(=O)(OCl3)2, t-BuOCl, NaOCl, chloramine-T, N-halosuccinamides, POX3, PX3, PX5 or metal halides; wherein X is Cl, Br, I or F, particularly Cl; ii) using at least one suitable oxidizing reagent: hydrogen peroxide, t-butyl hydroperoxide, tungstic peroxide, mchloroperbenzoic acid, benzoyl peroxide, hypohalous acid, ammonium ceric nitrate, ammonium hypoceric nitrate, oxone, periodic acid, hydrogen peroxide urea adduct, sodium perborate, Petition 870250083064, dated 09 / 15 / 2025, page 36 / 104 5 / 8 pyridinium chlorochromate and dimethyl sulfoxide;iii) using at least one acid selected from the group consisting of formic acid, acetic acid, triflic acid, benzoic acid, m-chlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, galeic acid, tartaric acid, ascorbic acid, hydrochloric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid and perchloric acid; iv) at a temperature in the range of 0 °C to 150 °C;(ev) using at least one solvent selected from the group consisting of hexane, heptane, octane, nonane, decane, dodecane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, toluene, xylene, mesitylene, benzene, diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglyceride, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramidan, 1,3-dimethyl-2-imidazolidinone, acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid and water.

12. Process according to claim 1, characterized in that process step (a) is carried out by mixing i) a mixture of the halogenating reagent and the oxidizing reagent and ii) a mixture of the dione of Formula II and the solvent, at a temperature in the range of 10 to 50 °C and then by heating to a temperature in the range of 15-150 °C.

13. Process according to claim 1, characterized in that process step (a) is performed by adding i) the oxidizing reagent and ii) the halogenating reagent separately in each sequence in portions or all at once to iii) a mixture of the dione of Formula II and the solvent, at a temperature in the range of 10 to 50 °C, followed by heating to a temperature in the range of 15-150 °C.

14. Process according to claim 1, characterized in that process step (b) is performed i) using at least one suitable reagent selected from the group consisting of formic acid, acetic acid, triflic acid, Petition 870250083064, dated 09 / 15 / 2025, page. 37 / 104 6 / 8 benzoic acid, m-chlorobenzoic acid, butyric acid, propionic acid, glycolic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, butyric acid, citric acid, oxalic acid, malonic acid, maleic acid, galeic acid, tartaric acid, ascorbic acid, hydrochloric acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, boronic acids, amberlysts, aluminum chloride, zinc chloride, trifluoroborone ether, zinc oxide, titanium tetrachloride, tin chloride, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, pyridine, N-methyl-2-pyrrolidone and N,N-dimethylmethanamide;ii) at a temperature in the range of 0 °C to 150 °C;and iii) using at least one solvent selected from the group consisting of formic acid, acetic acid, triflic acid, butyric acid, propionic acid, benzoic acid, m-chlorobenzoic acid, carbonic acid, glycolic acid and trifluoroacetic acid optionally in combination with at least one additional solvent selected from the group consisting of hexane, heptane, octane, nonane, decane, dodecane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, toluene, xylene, mesitylene, benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglycemic acid, diglymic acid, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramidan, 1,3-dimethyl-2-imidazolidinone and water.

15. Process for preparing anthranilic diamide of Formula I, according to claim 13, characterized in that R1 is CH3, Br or Cl; R2 is CN; Petition 870250083064, dated 09 / 15 / 2025, p. 38 / 104 7 / 8 R3a is H and R3b is methyl or 1-cyclopropyl ethyl; R3c is H; R4 is Br, or ^5(0)O-2; R5 is Cl; R6 is H or Cl; and Z is N.

16. Process according to claim 13, characterized in that process step (c) is performed i. using metal cyanides that are selected from sodium cyanide (NaCN), potassium cyanide (KCN), copper(I) cyanide (CuCN), zinc(II) cyanide (Zn(CN)2), sodium ferrocyanide (Na4Fe(CN)6), potassium hexacyanoferrate(III) (K3[Fe(CN)6]) or potassium hexacyanoferrate(II) (K4[Fe(CN)6]); ii. using the binder, which is selected from 1,2-dimethylethylenediamine (DMEDA), imidazole, 1-butyl-1H-imidazole, 2-picoline, 3-picoline, 2,6-lutidine, 1-methylpyrolidine or pyrolidine; iii. using the catalyst, which is a copper salt and is selected from copper(I) iodide (CuI), copper(I) chloride, copper(I) bromide, or copper acetate; iv. at a temperature in the range of 30 °C to 200 °C; and v.using at least one solvent selected from the group consisting of heptane, octane, nonane, decane, dodecane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, toluene, xylenes, mesitylene, benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglyceride, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)pyrimidinone, hexamethylphosphoramidan or 1,3-dimethyl-2-imidazolidinone.

17. Process, according to claim 13, characterized in that step a is performed using i) the halogenation reagent being HCl, HBr, SOCl2, NaOCl, NaOBr, Cl2 or Br2; Petition 870250083064, dated 09 / 15 / 2025, p.39 / 104 8 / 8 ii) at least one suitable oxidizing reagent selected from the group consisting of hydrogen peroxide, mchloroperbenzoic acid or periodic acid; iii) at least one acid selected from the group consisting of formic acid, acetic acid, triflic acid, benzoic acid, mchlorobenzoic acid, trifluoroacetic acid, para-toluenesulfonic acid, methanesulfonic acid, hydrochloric acid, hydroiodic acid, sulfuric acid, or perchloric acid; iv) at a temperature in the range of 5 °C to 80 °C; (ev) at least one solvent selected from the group consisting of toluene, xylene, t-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglycemic acid, diglymic acid, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, acetic acid, hydrochloric acid, hydrobromic acid, sulfuric acid or water.

18. Process according to claim 16, characterized in that i) the oxidation reagent and ii) the halogenation reagent are added separately in sequence in portions to iii) a mixture of the dione of Formula II and the solvent, at a temperature in the range of 10 to 50 °C, followed by heating to a temperature in the range of 15 to 150 °C. Petition 870250083064, dated 09 / 15 / 2025, p. 40 / 104