A method for the preparation of anthranyl diamides

Description

1 / 36 A METHOD FOR THE PREPARATION OF ANTHRANILIC DIAMIDES FIELD OF THE INVENTION

[0001] The present invention relates to a method for the preparation of substituted 1-pyridinylpyrazole-5-carboxylic acids of formula 3, their intermediates, N-oxides or salts thereof. Formula 3 where n is as described in this document.

[0002] In addition, the present invention relates to a method for the preparation of anthranilic diamide compounds of Formula 1, their intermediates, N-oxides or salts thereof. Formula 1 where R1, R2, R3 and R4 are as defined in this document. BACKGROUND OF THE INVENTION

[0003] 1-Pyridinylpyrazole-5-carboxylic acids are known to be important intermediates in the agrochemical industry, for example, for the synthesis of anthranilic diamides which are useful for protecting crops against pests. Petition 870250084693, dated 09 / 19 / 2025, p. 10 / 141 2 / 36 harmful. Several methods have been revealed by which these intermediates can be obtained.

[0004] Document WO 2019150220 discloses anthranilic diamides of Formula (I) and their use as insecticides, D4 in which, D represents D4; and Z1 is independently a direct linkage or CR6R7 or NRcou O or S(O)o-2; and E represents 4-membered heterocycles. It also provides a process for preparing so-called compounds of Formula (I).

[0005] Document WO 2022254395 discloses a process for preparing anthranilic diamides of Formula (I), Formula (I) where, Ra, Rb, R1, R2, R3, R4 and n are as defined in the description.

[0006] The process described in the prior art has shortcomings, such as a longer synthetic route, the use of additional agents such as halogenating agents, oxidizing agents and catalysts, making the process economically unviable, so it is not suitable for the commercial-scale preparation of anthranilic diamide compounds and intermediates of Petition 870250084693, dated 09 / 19 / 2025, page 11 / 141 3 / 36 same. Furthermore, the processes described in the prior art, namely in documents WO 2019150220 and WO 2022254395, involve Mitsunobu reactions for the preparation of the etherified product from ethyl 1-(3-chloropyridin-2-yl)-3-hydroxy-1H-pyrazol-5-carboxylate and thiethan-3-ol or 1,1-dioxide of 3-hydroxythiethane. Thus, these processes disclosed in the prior art have shortcomings, such as the application of moisture-free conditions, dry solvents, and expensive reagents, such as diethylazadicarboxylate (DEAD) or diisopropylazadicarboxylate (DIAD) and triphenylphosphine, necessary for carrying out the Mitsunobu reactions.

[0007] Therefore, there is a need for a scalable method that is simple, efficient, and economically viable and that overcomes at least one of the shortcomings associated with known methods.

[0008] The present invention provides an innovative method for the preparation of anthranilic diamides of Formula 1, their intermediates, N-oxides or salts thereof, preferably compounds of Formula 3, their intermediates, N-oxides or salts thereof, with good yield on a commercial scale, wherein the described method is shorter, more efficient, avoiding the use of additional agents such as halogenating agents, oxidizing agents and specific catalysts, as well as the Mitsunobu reaction itself. OBJECTIVE OF THE PRESENT INVENTION

[0009] The objective of the present invention is to provide a simple and economically viable method for the preparation of compounds of Formula 3, their intermediates, N-oxides or salts thereof, on a commercial scale.

[0010] Another objective of the present invention is to provide a simple, efficient and economically viable method for the preparation of anthranilic diamide compounds of Formula 1, their intermediates, N-oxides or salts thereof, on a commercial scale.

[0011] The present invention provides a solution to these objectives by offering an economical and high-yield method that allows the preparation of anthranilic diamide compounds of Formula 1 and / or key intermediates, a Petition 870250084693, dated 09 / 19 / 2025, page 12 / 141 4 / 36 know, compounds of Formula 3, to prepare such anthranilic diamide compounds of Formula 1, overcoming at least one of the shortcomings of the processes described in the prior art. SUMMARY OF THE INVENTION

[0012] The objectives of the present invention are achieved by providing an innovative, efficient and economically viable method for the preparation of compounds of Formula 3, their intermediates, N-oxides or salts thereof, Formula 3 is characterized by the fact that n is an integer selected from 0-2, comprising the following steps: a. prepare a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A); Formula 6 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Petition 870250084693, dated 09 / 19 / 2025, page 13 / 141 5 / 36 Formula 4, in which the Formula 4 compound is optionally isolated; n = 0-2 Formula 10 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3, Formula 4 El = 0-2

[0013] The present invention also provides a method for preparing anthranilic diamide compounds of Formula 1, their intermediates, N-oxides or salts thereof, in which, R1 is selected from hydrogen or C1-C1e alkyl; R2 is selected from C1-Ce alkyl or C3-C6 cycloalkyl, wherein said C1-Ce alkyl and C3-C6 cycloalkyl are optionally substituted with one or more substituents selected from a group consisting of halogen and C3-C6 cycloalkyl; Petition 870250084693, dated 09 / 19 / 2025, page 14 / 141 6 / 36 R3 is selected from hydrogen, halogen, or cyano; R4 is selected from halogen, C1-C1 alkyl, C1-C1 alkoxy or C1-C1 haloalkyl; en is an integer selected from 0-2, comprising the steps of: a. prepare a compound of Formula 5 from a compound of Formula 5 in the presence of a suitable reagent and a suitable solvent (A); Formula 6 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated; n = 0-2 Formula 10 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3; Petition 870250084693, dated 09 / 19 / 2025, page 15 / 141 7 / 36 Formula 4 η =0-2 d. react the compound of Formula 3 with an acid chloride in a suitable solvent (C) and a suitable base (II) to obtain the anthranilic diamide compound of Formula 1, its intermediates, N-oxides or salts thereof. DETAILED DESCRIPTION OF THE PRESENT INVENTION

[0014] As used in this document, the terms “comprises”, “that includes”, “includes”, “that includes” or any other variation thereof are intended to encompass a non-exclusive inclusion, subject to any explicitly stated limitation. For example, a process or method that comprises a list of elements is not necessarily limited to only those elements, but may include other elements not expressly listed or inherent to such process or method.

[0015] Furthermore, the indefinite articles "a" and "an" preceding an element or component of the present invention are intended to be non-restrictive with respect to the number of instances (i.e., occurrences) of the element or component. Therefore, "a" or "an" should be read as including one or at least one, and the singular form of the word for the element or component also includes the plural, unless the number is obviously considered singular.

[0016] The compounds of the present disclosure may be present in pure form or as mixtures of different possible isomeric forms, such as stereoisomers or constituent isomers. The various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers are within the scope of Petition 870250084693, dated 09 / 19 / 2025, page 16 / 141 8 / 36 claims of the present disclosure. A person skilled in the art will appreciate that a stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to other isomer(s) or when separated from other isomer(s). Furthermore, a person skilled in the art knows processes or methods or technology for selectively separating, enriching and / or preparing said isomers.

[0017] The compounds of the present disclosure may be present in the form of N-oxides or salts. The compounds of the present invention may be an acid addition salt or a base addition salt. The acid addition salt includes inorganic or organic acid, preferably hydrochloric acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid. The base addition salt includes an inorganic or organic base, preferably an alkali metal or alkaline earth metal salt.

[0018] The term C1-C6 alkyl used in the present invention refers to a linear or branched alkyl group with 1 to 6 carbon atoms, which may optionally be substituted by one or more substituents. Examples of C1-C6 alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, and n-hexyl.

[0019] The term C1-C6 alkoxy used in the present invention refers to a linear or branched alkyl group with 1 to 6 carbon atoms linked by an oxygen bond to the rest of the molecule, which may optionally be substituted by one or more substituents. Examples of C1-C6 alkoxy include, but are not limited to, methoxy, ethoxy and the like.

[0020] The halogen used in the present invention refers to fluorine, chlorine, bromine or iodine.

[0021] The term C1-C6 haloalkyl used in the present invention refers to a linear or branched alkyl with 1 to 6 carbon atoms that is substituted with one or more halogens and may optionally be substituted with one or more substituents. Examples include, but are not limited to, trifluoromethyl, difluoromethyl, trifluoroethyl, and perfluoroethyl. Petition 870250084693, dated 09 / 19 / 2025, p. 17 / 141 9 / 36

[0022] The term C3-C6 cycloalkyl used in the present invention refers to a non-aromatic saturated carbocyclic ring with 3 to 6 carbon atoms, which may optionally be substituted by one or more substituents. Examples of C3-C6 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0023] In the context of the present invention, the term optionally or optional when used in reference to any element, intermediates, reagents or conditions, including any method step, for example, the isolation of intermediates; is intended to mean that the element in question is isolated, or alternatively is not isolated from the reaction mixture and directly used for the subsequent chemical reaction. Similarly, this definition also applies in the case of reagents or reaction conditions.

[0024] The descriptive report in this document, the various features and advantageous details thereof are explained with reference to non-limiting examples in the description. The description of well-known components and processing techniques is omitted so as not to unnecessarily obscure the embodiments described in this document. The examples used in this document are intended merely to facilitate an understanding of the ways in which the descriptive report in this document can be practiced and to further enable those skilled in the art to practice the descriptive report in this document. Consequently, the examples should not be interpreted as limiting the scope of the descriptive report in this document.

[0025] The description of the specific modalities will reveal so completely the general nature of the modalities in the present document that others may, applying current knowledge, readily modify and / or adapt such specific modalities for various applications without departing from the generic concept and, therefore, such adaptations and modifications must and are intended to be understood within the meaning and range of equivalents of the modalities revealed. It should be understood that the phraseology or terminology employed in Petition 870250084693, dated 09 / 19 / 2025, page 18 / 141 10 / 36 This document is for descriptive purposes only and not for limitation. Therefore, although the embodiments in this document have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments in this document may be practiced with modification within the spirit and scope of the embodiments as described in this document.

[0026] Any discussion of documents, acts, materials, devices, articles and the like that have been included in this descriptive report is for the sole purpose of providing context for the disclosure. It should not be taken as an admission that any or all of these matters form part of the basis of the prior art or were common knowledge in the field relevant to the disclosure, as they existed anywhere prior to the priority date of this application.

[0027] Consequently, the present invention provides a method for the preparation of a compound of Formula 3, its intermediates, N-oxides or salts thereof, Formula 3 is characterized by the fact that n is an integer selected from 0-2, comprising the following steps: a. prepare a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A); Petition 870250084693, dated 09 / 19 / 2025, p. 19 / 141 11 / 36 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated; and Formula 10 n = 0-2 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain the compound of Formula 3. Formula 4

[0028] The present invention also provides a method for preparing anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, Petition 870250084693, dated 09 / 19 / 2025, page 20 / 141 12 / 36 in which, R1 is selected from hydrogen or C1-C1e alkyl; R2 is selected from C1-Ce alkyl or C3-C6 cycloalkyl, wherein said C1-Ce alkyl and C3-C6 cycloalkyl are optionally substituted with one or more substituents selected from a group consisting of halogen and C3-Ce cycloalkyl; R3 is selected from hydrogen, halogen, or cyano; R4 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy or C1-C6 haloalkyl; en is an integer selected from 0-2, comprising the steps of: a. prepare a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A); Formula 6 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated; Petition 870250084693, dated 09 / 19 / 2025, p. 21 / 141 13 / 36 n = 0-2 Formula 4 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3; and Formula 4 Formula 3 d. react the compound of Formula 3 with an acid chloride in a suitable solvent (C) and a suitable base (II) to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof.

[0029] The present invention also provides a method for preparing the anthranilic diamide compound of Formula 1, its intermediates, N-oxides or salts thereof, in which, R1 is selected from hydrogen or C1-C1e alkyl; R2 is selected from either C1-C1e alkyl or C1-C1e cycloalkyl, wherein said C1-C6 alkyl and C1-C6 cycloalkyl are optionally replaced with one or Petition 870250084693, dated 09 / 19 / 2025, page 22 / 141 14 / 36 more substituents selected from a group consisting of halogen and C3-C6 cycloalkyl; R3 is selected from hydrogen, halogen, or cyano; R4 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy or C1-C6 haloalkyl; en is an integer selected from 0-2, comprising the steps of: a. prepare a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A); Formula 6 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated; Formula 10 n = 0-2 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3; and Petition 870250084693, dated 09 / 19 / 2025, page 23 / 141 15 / 36 Formula 4 η = 0-2 Formula 3 d. (i) react the compound of Formula 3 with an acid chloride in a suitable solvent (C) to form an acid chloride of Formula 3A, followed by coupling with a compound of Formula 9 using a suitable base (II) and a suitable solvent (D), to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof. Formula 3, n = 0-2

[0030] The present invention also provides a method for preparing the anthranilic diamide compound of Formula 1, its intermediates, N-oxides or salts thereof, in which, R1 is selected from hydrogen or C1-C1e alkyl; Petition 870250084693, dated 09 / 19 / 2025, page 24 / 141 16 / 36 R2 is selected from C1-Ce alkyl or C3-C6 cycloalkyl, wherein said C1-Ce alkyl and C3-C6 cycloalkyl are optionally substituted with one or more substituents selected from a group consisting of halogen and C3-Ce cycloalkyl; R3 is selected from hydrogen, halogen, or cyano; R4 is selected from halogen, C1-C1 alkyl, C1-C1 alkoxy or C1-C1 haloalkyl; en is an integer selected from 0-2, comprising the steps of: a. prepare a compound of Formula 5 from a compound of Formula 5 in the presence of a suitable reagent and a suitable solvent (A); Formula 6 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated; Formula 5 Formula 10 n = 0-2 Formula 4 Formula 4 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3; Petition 870250084693, dated 09 / 19 / 2025, page 25 / 141 17 / 36 η = 0-2 (d) (ii) react the compound of Formula 3 with a compound of Formula 7 in the presence of a suitable base (II) and an acid chloride to form a compound of Formula 2, in which the compound of Formula 2 is optionally isolated; and open the ring of the compound of Formula 2 with a compound of Formula 8 in the presence of a suitable base (III) in a suitable solvent (C) to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, Formula 2 Formula 1

[0031] The present invention also provides a method for preparing the anthranilic diamide compound of Formula 1, its intermediates, N-oxides or salts thereof, in which, Petition 870250084693, dated 09 / 19 / 2025, p. 26 / 141 18 / 36 R1 is selected from hydrogen or C1-C1e alkyl; R2 is selected from C3-C6 alkyl or C3-C6 cycloalkyl, wherein said C1-C6 alkyl and C3-C6 cycloalkyl are optionally substituted with one or more substituents selected from a group consisting of halogen and C3-C6 cycloalkyl; R3 is selected from hydrogen, halogen, or cyano; R4 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy or C1-C6 haloalkyl; en is an integer selected from 0-2, comprising the steps of: a. prepare a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A); Formula 6 Formula 5 b. react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, in which the Formula 4 compound is optionally isolated; Formula 10 n = 0-2 c. hydrolyze compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3; and Petition 870250084693, dated 09 / 19 / 2025, p. 27 / 141 19 / 36 Formula 4 η = 0-2 d. (I) react the compound of Formula 3 with an acid chloride in a suitable solvent (C) to form an acid chloride of Formula 3A, followed by coupling with a compound of Formula 9 using a suitable base (II) and a suitable solvent (D), to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, Formula 3, n=0-2 OR d. (ii) reacting the compound of Formula 3 with a compound of Formula 7 in the presence of a suitable base (II) and an acid chloride to form a compound of Formula 2, in which the compound of Formula 2 is optionally isolated; and opening the ring of the compound of Formula 2 with a compound of Formula 8 in the presence of a suitable base (III) in a suitable solvent (C) to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, Petition 870250084693, dated 09 / 19 / 2025, p. 28 / 141 20 / 36 Formula 3 Formula 7 Formula 2 Formula 1

[0032] In one embodiment, n = 2 for Formula 1, Formula 2, Formula 3, Formula 4 and Formula 10 of the present methods.

[0033] In one embodiment, the present invention provides a method for preparing the anthranilic diamide compound of Formula 1, wherein R1 is H or C1-C2 alkyl; R2 is C1-C4 alkyl; R3 is fluorine or chlorine; and R4 is chlorine or C1-C2 alkyl.

[0034] In a preferred embodiment, the present invention provides a method for preparing the anthranilic diamide compound of Formula 1, wherein R1 is H; R2 is isopropyl or tert-butyl; R3 is chlorine; and R4 is methyl.

[0035] In a preferred embodiment, the Formula 3 compound is prepared from the Formula 5 compound without isolating the Formula 4 compound.

[0036] According to one embodiment of the present invention, the conversion of the Formula 5 compound to the Formula 3 compound can be carried out in a single step without isolating the Formula 4 compound.

[0037] In one embodiment of the present invention, the compound of Formula 3 is converted in-situ into compound of Formula 3A in the presence of a suitable acid chloride and a suitable solvent (C). Petition 870250084693, dated 09 / 19 / 2025, page 29 / 141 21 / 36

[0038] In another embodiment of the present invention, the acid chloride of Formula 3A in step-d can be isolated before reacting with the compound of Formula 9. where R1, R2, R3, R4 and n are as described above.

[0039] In one embodiment, the present invention provides the acid chloride of the compound of Formula 3 and is represented as compound of Formula 3A, Formula 3A where n is an integer selected from 0-2, preferably n is 2.

[0040] In another embodiment, the present invention provides a method for preparing a compound of Formula 4, wherein the method comprises the step of (step-b): react a compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated, Petition 870250084693, dated 09 / 19 / 2025, p. 30 / 141 22 / 36 Formula 10 η = 0-2

[0041] Alternatively, the acid chloride of the compound of Formula 3 can be generated in situ and then reacted with a compound of Formula 9 to obtain the anthranilic diamide compound of Formula 1, its intermediates, Noxides or salts thereof.

[0042] The compound of Formula 10 is obtained from a commercial source or can be synthesized according to known methods, as described in PCT application PCT / IN2023 / 051201, according to the following reaction scheme:

[0043] The suitable base selected from base (I), base (II) or base (III), used in the present invention, may be selected independently from an organic or inorganic base.

[0044] The inorganic base is selected, in a non-limiting manner, from alkali metal hydrogen carbonates such as lithium hydrogen carbonate (LiHCOs), sodium hydrogen carbonate (NaHCOs), potassium hydrogen carbonate (KHCO3) and cesium hydrogen carbonate (CsHCOs); alkali / alkaline earth metal carbonates such as sodium carbonate (Na2COs), calcium carbonate (CaCOs), cesium carbonate (CS2CO3), lithium carbonate (Li2CO3), potassium carbonate (K2CO3); alkali / alkaline earth metal hydroxides such as lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), calcium hydroxide (Ca(OH)2), alkali metal phosphates such as sodium diphosphate (Na2HPO4), sodium phosphate (NasPCU), Petition 870250084693, dated 09 / 19 / 2025, p. 31 / 141 23 / 36 potassium diphosphate (K2HPO4), potassium phosphate (K3PO4); alkali metal halides such as sodium fluoride (NaF), potassium fluoride (KF) and cesium fluoride (CsF); alkali metal hydrides such as lithium hydride (LiH), sodium hydride (NaH) and potassium hydride (KH); and alkali metal alkoxides such as sodium methoxide (NaOCH3), sodium ethoxide (NaOCH2CH3), sodium tert-butoxide and potassium tert-butoxide and the like.

[0045] The organic base is selected, in a non-limiting manner, from amines such as ethylamine, triethylamine, isopropylamine, diisopropylamine, triisopropylamine, pyridine, picoline, piperidine, methylmorpholine, N-methylpiperidine N,N-(dimethylamino)pyridine (DMAP), lutidine, colidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide and choline hydroxide; Amidines including, but not limited to, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 2,3,4,6,7,8,9,10-octahydropyrimidol[1,2-a]azepine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), and 1,4-diazabicyclo[2.2.2]octane (DABCO, triethylenediamine).

[0046] The suitable solvent selected from solvent (A), solvent (B), solvent (C) or solvent (D), used in the present invention, may be independently selected from aliphatic or aromatic hydrocarbons, halogenated hydrocarbons, ethers, cyclic ethers, nitriles, amides, ketones, acids, alcohols, water or mixtures thereof.Preferably, the solvent used in the present method may be selected, but not limited to, acetonitrile, acetic acid, acetone, hexane, heptane, octane, nonane, decane, dodecane, cycloalkanes such as cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane and cyclooctane; N,N-dimethylformamide, ethylene dichloride, ethyl acetate, toluene, xylene, mesitylene, benzene, halogenated benzene, diisopropyl ether, t-butyl methyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, monoglyme, diglyme, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane, dichloromethane, chloroform, dichloroethane, N,Ndimethylmethanamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, 1,3-dimethyl. Petition 870250084693, dated 09 / 19 / 2025, page 32 / 141 24 / 36 3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone, or combinations thereof.

[0047] The method for preparing a compound of Formula 3 or Formula 1, wherein the steps of said method - step-a, step-b, step-c and step-d - are carried out at a temperature in a range of 0 to 150 °C.

[0048] The suitable reagent for step-a of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, is selected from, but not limited to, nitric acid (HNO3), sulfuric acid, acetic acid, hydrochloric acid, or mixtures thereof. In a preferred embodiment, the suitable reagent used in step-(a) is nitric acid (HNO3), preferably 70% HNO3.

[0049] In a preferred embodiment, the suitable solvent (A) in step (a) of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, is selected from dichloromethane, dichloroethane or acetonitrile, preferably dichloroethane.

[0050] In a preferred embodiment, step (a) of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, is generally carried out at a temperature in a range of 0 to 100 °C, preferably between 0 and 40 °C.

[0051] In another preferred embodiment, step a of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, where i. the appropriate reagent in step-a of the method is selected from nitric acid (HNO3), sulfuric acid, acetic acid, hydrochloric acid or mixtures thereof; ii. the appropriate solvent (A) in step-a of the method is selected from dichloromethane, dichloroethane or acetonitrile; iii. Step a of the method is carried out at a temperature in the range of 0 to 100 °C. Petition 870250084693, dated 09 / 19 / 2025, page 33 / 141 25 / 36

[0052] In a preferred embodiment, the suitable base (I) in step-(b) of the method for preparing a compound of Formula 3 or Formula 1 as disclosed herein, is selected from, but not limited to, alkali or alkaline earth metal carbonates or bicarbonates, alkali / alkaline earth metal hydroxides, alkali metal phosphates, alkali metal alkoxides or alkali metal hydrides; preferably K2CO3, Na2CO3, NaOH, KOH or K3PO4; more preferably K2CO3, KOH or K3PO4.

[0053] In a preferred embodiment, the suitable solvent (B) for step (b) of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, is selected from, but not limited to, dichloroethane, toluene, xylenes, chlorinated benzene, acetonitrile and dioxane, dimethoxyethane; preferably monochlorobenzene / dichlorobenzene / chlorobenzene.

[0054] In a preferred embodiment, the phase transfer catalyst, if used in step-(b) of the current methods, is selected from tetraalkylammonium halide, preferably tetrabutylammonium bromide.

[0055] In a preferred embodiment, the suitable temperature for step-(b) of the method for preparing a compound of Formula 3 or Formula 1 as disclosed herein is in the range of 25 to 130 °C, preferably between 25 and 105 °C.

[0056] In another preferred embodiment, step b of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, where i. the appropriate base (I) in step-b of the method is selected from K2CO3, Na2CO3, NaOH, KOH or K3PO4; ii. the suitable solvent (B) in step b of the method is selected from dichloroethane, toluene, xylenes, chlorinated benzene, acetonitrile, dimethoxyethane and dioxane; iii. the optional phase transfer catalyst is selected from tetra-alkylammonium halide; Petition 870250084693, dated 09 / 19 / 2025, page 34 / 141 26 / 36 iv. Step b of the method is carried out at a temperature in the range of 25 to 130 °C.

[0057] The suitable hydrolyzing agent used in step (c) of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, is an acid. In a preferred embodiment, the acid used for the hydrolysis of the ester in step (c) is selected from, but not limited to, aqueous sulfuric acid (aqueous H2SO4) and hydrochloric acid (HCl). In a more preferred embodiment, the hydrolyzing agent used in step (c) of the present invention is 10-50% aqueous sulfuric acid; preferably 20% aqueous H2SO4.

[0058] The suitable solvent for hydrolysis in step (c) of the method for preparing a compound of Formula 3 or Formula 1 as disclosed herein is selected from, but not limited to, acetic acid (AcOH), water or acetonitrile; preferably acetic acid (AcOH).

[0059] In a preferred embodiment, the suitable temperature for step-(c) of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, is in the range of 50 to 130 °C, preferably between 70 and 105 °C.

[0060] In another preferred embodiment, step-c of the method for preparing a compound of Formula 3 or Formula 1, as disclosed herein, where i. the hydrolyzing agent in step c of the method is selected from an acid; ii. the appropriate solvent in step c of the method is selected from acetic acid (AcOH), water or acetonitrile; iii. Step c of the method is carried out in a temperature range of 50 to 130 °C.

[0061] The acid chloride used in step-(d), step-(d(i)) or step-(d(ii)) of the method for preparing a compound of Formula 1, as disclosed herein, is selected from, but not limited to, thionyl chloride (SOCl2), mesityl chloride (MsCl, methanesulfonyl chloride), pentachloride of Petition 870250084693, dated 09 / 19 / 2025, page 35 / 141 27 / 36 phosphorus (PCI5), phosphorus trichloride (PCI3), oxalyl chloride, triphosgene and phosgene. In a preferred embodiment, the acid chloride is selected from thionyl chloride (SOCl2), mesityl chloride (MsCl) or phosgene (COCl2).

[0062] In a preferred embodiment, the base (II) and base (III) used in step-(d), step-(d(i)) or step-(d(ii)) of the method of preparing a compound of Formula 1, as disclosed herein, are selected independently, but are not limited to, an inorganic base, such as carbonate, bicarbonate, hydroxide, hydrides or alkoxide of alkali or alkaline earth metals; organic base, such as isopropyl amine, triethylamine, diisopropyl ethyl amine, triisopropyl amine, pyridine, picoline, N-methylmorpholine, Nmethylpiperidine, N,N-(dimethylamino)pyridine (DMAP), lutidine, collidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide; amidines, such as 1,8diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN). In a more preferred embodiment, base (II) and base (III) are independently selected from triethylamine, isopropylamine, pyridine, picoline or mixtures thereof.

[0063] In a preferred embodiment, the suitable solvent (C) and the solvent (D) in step-(d), step-(d(i)) or step-(d(ii)) of the method for preparing a compound of Formula 1 as disclosed herein, are independently selected from dichloroethane, acetonitrile (ACN), N,N-dimethylformamide (DMF), ethyl acetate, pyridine, picoline or mixtures thereof.

[0064] The reaction temperature for carrying out step-(d), step-(d(i)) and step-(d(ii)) of the method for preparing a compound of Formula 1, as disclosed herein, is in the range of 0 to 80 °C.

[0065] In another preferred embodiment, step-d, step-(d(i)) or step-(d(ii)) of the method for preparing a compound of Formula 1, as disclosed herein, wherein Petition 870250084693, dated 09 / 19 / 2025, page 36 / 141 28 / 36 i. The acid chloride in step-d, step-(d(i)) or step-(d(ii)) of the method is selected from thionyl chloride (SOCl2), mesityl chloride (MsCl), phosphorus pentachloride (PCl5), phosphorus trichloride (PCl3), oxalyl chloride, triphosgene or phosgene; ii. the suitable solvent (C) and the solvent (D) in step-d of the method, step-(d(i)) or step-(d(ii)) are selected independently from dichloroethane, acetonitrile (ACN), N,N-dimethylformamide (DMF), ethyl acetate, pyridine, picoline or mixtures thereof; iii. the suitable base (II) and the base (III) in step-d, step-(d(i)) or step-(d(ii)) of the method are selected independently from alkali or alkaline earth metal carbonate, bicarbonate, hydroxide, hydrides or alkoxide, isopropyl amine, triethylamine, diisopropyl ethyl amine, triisopropyl amine, pyridine, picoline, N-methylmorpholine, N-methylpiperidine, N,N-(dimethylamino)pyridine (DMAP), lutidine, colidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) or 1,5diazabicyclo[4.3.0]non-5-ene (DBN); iv. step-d, step-(d(i)) or step-(d(ii)) of the method is carried out at a temperature within a range of 0 to 80 °C.

[0066] Reaction time is not critical and depends on batch size, temperature, type of reaction, solvent and reagents used and is generally from a few minutes to a few hours.

[0067] The methods disclosed in the present invention for the preparation of the anthranilic diamides of Formula 1, the intermediates of Formula 3, Formula 4, or their respective N-oxides or salts, as described above, employ easy conversions, readily available starting materials, reagents, and reaction conditions, making them suitable for commercial-scale applications. Furthermore, the methods disclosed in the present invention provide the Petition 870250084693, dated 09 / 19 / 2025, page 37 / 141 29 / 36 intermediate component required and the final compound with high yield and chemical purity.

[0068] A person skilled in the art knows the best procedures for processing reaction mixtures after the respective reactions have ended. Processing is generally carried out by isolating the product, and optionally washing with solvents, and also optionally drying the product if useful or necessary.

[0069] According to the methods disclosed in the present invention, the products obtained in individual steps can be isolated or, alternatively, not isolated from the reaction mixture and used directly for the subsequent reaction step. The isolation of the reaction products can be carried out by means of a technique that includes, but is not limited to, decantation, filtration, centrifugation, evaporation, liquid-liquid extraction, distillation, recrystallization, chromatography and the like, or a combination thereof.

[0070] The reaction steps according to the invention are generally carried out under atmospheric pressure. Alternatively, however, it is also possible to carry out the reaction steps of the present method under reduced pressure or higher pressure.

[0071] The invention is further illustrated by the following examples which are provided as illustrative of the invention, and do not limit the scope of the invention. Although the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and should be included within the scope of the present invention.

[0072] The present invention provides a method for preparing anthranilic diamides of Formula 1, the intermediates of Formula 3, Formula 4 or their respective N-oxides or salts, as described above, wherein the steps can be carried out in a batch, semi-continuous or continuous reaction mode, specifically also under semi-continuous or continuous flow reaction conditions. Petition 870250084693, dated 09 / 19 / 2025, page 38 / 141 30 / 36

[0073] Although the subject has been described in considerable detail with reference to certain examples and implementations, other implementations are possible. EXAMPLES

[0074] The disclosure will now be illustrated with working examples, which are intended to illustrate the workings of the disclosure and are not intended to restrict or imply any limitations on the scope of the present disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as that commonly understood by an individual of ordinary skill in the art to which this disclosure pertains. Although methods and materials similar or equivalent to those described herein may be used in the practice of the disclosed methods and compositions, exemplary methods, devices, and materials are described herein. It should be understood that this disclosure is not limited to the specific methods and experimental conditions described, as such methods and conditions may be applicable. Experimental Examples: Scheme 1: Preparation of the anthranilic diamide compound of Formula 1

[0075] All solvents and reagents used in the present invention are obtained from commercial sources. Reagents such as ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylate (compound of Formula 6), reagents based on Petition 870250084693, dated 09 / 19 / 2025, page 39 / 141 31 / 36 Anthranilic acid (compounds of Formula 7) and amines of Formula 8 were obtained from commercial suppliers or prepared according to a procedure known from the literature. The amine of Formula 9 was prepared according to a procedure from the literature or as described in the prior art, for example, documents WO 2020170092 and WO 2022064454. Example 1: Preparation of the anthranilic diamide compound of Formula 1 Step a: Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-hydroxy-1H-pyrazol-5-carboxylate

[0076] To a stirred suspension of ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (compound of Formula 6, 100 g, 371 mmol) in dichloroethane (500 ml), 70% aqueous nitric acid (16.7 g, 185 mmol) was added at 0-5 °C. The temperature of the reaction mass was increased to 20-30 °C, and stirring was continued. After completion of the reaction, the reaction mass was cooled to 0-5 °C. The resulting solid was filtered, washed with water (500 ml), and dried to yield ethyl 1-(3-chloropyridin-2-yl)-3-hydroxy-1H-pyrazol-5-carboxylate (Formula 5) (68 g, 68% yield).

[0077] 1H NMR (DMSO-d6, 400MHz): δ 8.12-8.10 (dd, J = 1.6 Hz, 1H), 7.847.82 (dd, J = 1.6 Hz, 1H), 6.98-6.95 (dd, J = 4.8 Hz, 1H), 5.28-5.23 (m, m / z = 348.0 [M+H]+. Step-b: Synthesis of ethyl 1-(3-chloropyridin-2-yl)-3-((1,1-dioxidothietan-3-yl)oxy)-1Hpyrazol-5-carboxylate Method 1: Reaction using potassium carbonate as a base Petition 870250084693, dated 09 / 19 / 2025, page 40 / 141 32 / 36 OH Cl

[0078] To a stirred suspension of ethyl 1-(3-chloropyridin-2-yl)-3-hydroxy-1H-pyrazol-5-carboxylate (86 g, 300 mmol) in chlorobenzene (172 ml), potassium carbonate (2.0 eq., 85 g, 600 mmol) was added at 25-30 °C. The temperature of the reaction mass was increased to 70-75 °C, and stirring was continued for a further 45 minutes. To this reaction mass, a solution of 3-chlorothiieethane 1,1-dioxide (Formula 10) (2.0 eq., 89 g, 600 mmol) in chlorobenzene (172 ml) was added at 70-75 °C. The temperature of the reaction mass was increased to 80-85 °C and stirring continued for a further 3 h. After the reaction was complete, the reaction mass was cooled to 60-65 °C and filtered. The filtrate was concentrated under reduced pressure to obtain ethyl 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3yl)oxy)-1H-pyrazol-5-carboxylate (Formula 4) (135.7 g) as a crude product which was used in step-c. HPLC purity (%) - 86.6; MS- m / z 371 [M+H]+. Method 2: Reaction using tribasic potassium phosphate as a base

[0079] To a stirred suspension of ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (5 g, 18.7 mmol) in chlorobenzene (50 ml), 3-chlorothiethane 1,1-dioxide (15.01 g, 37.4 mmol), tetrabutylammonium bromide (1.5 g, 4.7 mmol) and tribasic potassium phosphate (13.9 g, 65.4 mmol) were added at 25–30 °C. The temperature of the reaction mass was increased to 80–85 °C, and stirring continued for 30 h. After completion of the reaction, the reaction mass was cooled to 60–65 °C and filtered. The filtrate was concentrated under reduced pressure to obtain ethyl 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxylate (Formula 4) (11.9 g, 77% yield). Method 3: Reaction using potassium hydroxide as a base Petition 870250084693, dated 09 / 19 / 2025, page 41 / 141 33 / 36

[0080] To a stirred suspension of ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate (0.5 g, 1.868 mmol) in chlorobenzene (5 ml), 3-chlorothiethane 1,1-dioxide (0.52 g, 3.74 mmol), tetrabutylammonium bromide (0.15 g, 0.47 mmol) and potassium hydroxide (0.26 g, 4.67 mmol) were added at 25–30 °C. The temperature of the reaction mass was increased to 80–85 °C, and stirring continued for 24 h. After completion of the reaction, the reaction mass was cooled to 60–65 °C and filtered. The filtrate was concentrated under reduced pressure to obtain ethyl 1-(3-chloropyridin-2-iI)-3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxylate (Formula 4) as a crude product which was used in the next step. Step-c: Synthesis of 1-(3-chloropyridin-2-yl)-3-((1,1-dioxidothietan-3yl)oxy)-1H-pyrazol-5-carboxylic acid (Formula 3): Molecular weight: 371.79 Molecular weight: 343.74

[0081] In a stirred mixture of acetic acid (80 ml) and ethyl 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxylate (crude product from step-b, method 1,135.7 g), 20% aqueous sulfuric acid (400 ml) was added. The temperature of the reaction mass was increased to 95-100 °C, and stirring continued for 24 h. After the reaction was complete, the reaction mass was cooled to 0-5 °C. The solid obtained was washed with water (172 ml) and dried to obtain 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxylic acid (72 g, 60% yield) (Formula 3).

[0082] 1H-NMR (400 MHz, Chloroform-D) δ 8.48 (dd, J = 4.7, 1.7 Hz, 1H), 7.93 (dd, J = 8.3, 1.5 Hz, 1H), 7.44 (dd, J = 8.1,4.7 Hz, 1H), 6.58 (s, 1H), 5.38-5.32 (m, 1H), 4.61-4.55 (m, 2H), 4.37-4.31 (m, 2H). MS: m / z = 343.0 [M+H]+. Petition 870250084693, dated 09 / 19 / 2025, p. 42 / 141 34 / 36 Stage-b and Stage-c In-situ: In situ preparation of 1-(3-chloropyridin-2-yl)3-((1,1-dioxydothiethane-3-yl)oxy)-1H-pyrazol-5-carboxylic acid from 1-(3chloropyridine-2-yl)-3-hydroxy-1H-pyrazol-5-ethyl carboxylate

[0083] To a stirred suspension of ethyl 1-(3-chloropyridin-2-yl)-3-hydroxy-1H-pyrazol-5-carboxylate, 3-chlorothiethane 1,1-dioxide (2.0 eq., 26.3 g, 185 mmol) and potassium carbonate (1.2 eq., 15.65 g, 111 mmol), chlorobenzene (50 ml) was added at 25-30 °C. The temperature of the reaction mass was increased to 70-80 °C, and stirring continued for 3 h. After completion of the reaction, the reaction mass was cooled to 25-30 °C. Acetic acid (25 ml) and 20% aqueous sulfuric acid (125 ml) were added to the above suspension. The temperature of the reaction mass was increased to 95-100 °C, and the mixture was stirred for 24 hours. After the reaction was complete, the reaction mass was cooled to 0-5 °C, stirred for 1-2 h, and the resulting solid was filtered, washed with water (100 ml), and dried to produce 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxylic acid (Formula 3) (16.8 g, 48.9 mmol, 90.29% yield). Step-d: Synthesis of N-(2-(tert-butylcarbamoyl)-4-chloro-6-methylphenyl)-1-(3chloropyridin-2-yl)-3-((1,1-dioxidothietan-3-yl)oxy)-1H-pyrazol-5-carboxamide (Formula 1)

[0084] A suspension of 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3yl)oxy)-1H-pyrazole-5-carboxylic acid (1.2 g, 3.09 mmol) and 2-amino-N-(tert-butyl)-5-chloro-3-methylbenzamide (Formula 9) (1.05 eq, 0.8 g, 3.24 mmol) in acetonitrile Petition 870250084693, dated 09 / 19 / 2025, pp. 43 / 141 A 35 / 36 ml (6 ml) solution was cooled to 0-5 °C and stirred for 10-15 minutes. To this suspension, 3-methylpyridine (2.301 g, 2.4 ml, 24.70 mmol) was added dropwise over a period of 5 minutes, and stirring continued for 10-15 minutes, followed by the dropwise addition of methanesulfonyl chloride (1.061 g, 0.717 ml, 9.26 mmol) over a period of 5 minutes. The temperature of the reaction mass was slowly increased to 25-30 °C, and stirring continued for a further 5 h. After completion of the reaction, the reaction mass was concentrated under reduced pressure to remove the acetonitrile and obtain a residue. Acetone (3 ml) and water (5 ml) were added to the residue, and the mixture was stirred at 0-5 °C. The solid obtained was filtered, washed with water (5 ml) and dried to produce N-(2-(tert-butylcarbamoyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-3-((1,1-dioxidothiethane-3yl)oxy)-1H-pyrazol-5-carboxamide (Formula 1) (1.4 g, 2.472 mmol, 80.04% yield). MS: m / z = 566.0 [M+H]+. Alternative stage: Síntese de 6-cloro-2-(1-(3-chloropyridin-2-yl)-3-((1,1-dioxidotietan-3-yl)oxi)-1Hpyrazol-5-yl)-8-metil-4H-benzo[d][1,3]oxazin-4-ona

[0085] A stirred suspension of 1-(3-chloropyridin-2-yl)-3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxylic acid (Formula 3) (50.0 g, 131 mmol) and 2-amino-5-chloro-3-methylbenzoic acid (Formula 7) (25.6 g, 138 mmol) in acetonitrile (400 ml) was cooled to 0-10 °C, and pyridine (83 g, 1052 mmol) was added at 0-10 °C. To this reaction mixture, methanesulfonyl chloride (45.2 g, 394 mmol) was added dropwise at 0-10 °C. The resulting reaction mixture was stirred for 1-2 hours at 25-30 °C. After the reaction was complete, the reaction mixture was cooled to 0-5 °C and filtered. The filter cake was washed with water (125 g) and dried under reduced pressure to obtain 6-chloro-2-(1-(3-chloropyridin-2-yl)-3-((1,1-dioxidothiethane-3-yl)oxy)-1H-pyrazol-5-yl)-8-methyl-4Hbenzo[d][1,3]oxazin-4-one (Formula 2) (63 g, 97% yield). Synthesis of N-(2-(tert-butylcarbamoyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin2-yl)-3-((1,1-dioxidothietan-3-yl)oxy)-1H-pyrazol-5-carboxamide Petition 870250084693, dated 09 / 19 / 2025, p. 44 / 141 36 / 36

[0086] To a stirred suspension of 6-chloro-2-(1-(3-chloropyridin-2-yl)-3-((1,1-dioxidothiethane-3-yl)oxy)-1H-pyrazol-5-yl)-8-methyl-4H-benzo[d][1,3]oxazin-4-one (43.5 g, 87 mmol) in N,N-dimethylformamide (87 ml), tert-butylamine (Formula 8) (9.58 g, 131 mmol) was added dropwise over 30–40 minutes at 10–20 °C. The reaction mixture was stirred for 6–8 hours at 25–30 °C. After completion of the reaction, the excess tert-butylamine was distilled from the reaction mixture under reduced pressure. Isopropanol (304.5 ml) was added to the residue, and the resulting reaction mixture was stirred for 6-8 hours at 25-30 °C. The solid obtained was filtered, the resulting wet cake was washed with acetone (87 ml) and dried under reduced pressure to obtain N-(2-(tert-butylcarbamoyl)-4-chloro-6-methylphenyl)-1-(3-chloropyridine-2-yl)3-((1,1-dioxythiethan-3-yl)oxy)-1H-pyrazol-5-carboxamide (Formula 1) (43 g, 86% yield). Petition 870250084693, dated 09 / 19 / 2025, p. 45 / 141

Claims

1 / 9 CLAIMS 1. Method for preparing a compound of Formula 3, its intermediates, N-oxides or salts thereof, Formula 3 characterized in that n is an integer selected from 0-2, comprising the steps of: a. preparing a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A), b. reacting the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated, Petition 870250084693, dated 19 / 09 / 2025, page 46 / 141 2 / 9 c. Hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain the compound of Formula 3, Formula 4 η = 0-2 Hydrolysis Formula 3 η = 0-2 2. Method for preparing the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, characterized in that R1 is selected from hydrogen or C1-C6 alkyl; R2 is selected from C1-C6 alkyl or C3-C6 cycloalkyl, wherein said C1-C6 alkyl and C3-C6 cycloalkyl are optionally substituted with one or more substituents selected from a group consisting of halogen and C3-C6 cycloalkyl; R3 is selected from hydrogen, halogen or cyano; R4 is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy or C1-C6 haloalkyl; en is an integer selected from 0-2, comprising the steps of: a. preparing a compound of Formula 5 from a compound of Formula 6 in the presence of a suitable reagent and a suitable solvent (A); Petition 870250084693, dated 09 / 19 / 2025, page 47 / 141 3 / 9 b.react the compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated, Formula 10 n = 0-2 Formula 4 c. hydrolyze the compound of Formula 4 in the presence of a hydrolyzing agent to obtain a compound of Formula 3, Formula 4 n = 0-2 Formula 3; and d. react the compound of Formula 3 with an acid chloride in a suitable solvent (C) and a suitable base (II) to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof.

3. Method according to claim 2, characterized in that, in step-d, the compound of Formula 3 is reacted with an acid chloride in a suitable solvent (C) to form an acid chloride of Formula 3A, followed by coupling with a compound of Formula 9 using a suitable base (II) and a suitable solvent (D), to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, Formula 3, n = 0-2 wherein R1, R2, R3, R4 and n are as defined in claim 2.

4. Method according to claim 2, characterized in that, in step-d, the compound of Formula 3 is reacted with a compound of Formula 7 in the presence of a suitable base (II) and an acid chloride to form a compound of Formula 2, wherein the compound of Formula 2 is optionally isolated; and ring opening of the compound of Formula 2 with a compound of Formula 8 in the presence of a suitable base (III) in a suitable solvent (C) to obtain the anthranilic diamide of Formula 1, its intermediates, N-oxides or salts thereof, Formula 7 Formula 3 Formula 2 Formula 1 wherein R1, R2, R3, R4 and are as defined in claim 2.

5. A method according to any one of claims 2-4, characterized in that R1 is H or C1-C2 alkyl; R2 is C1-C4 alkyl; R3 is fluorine or chlorine; and R4 is chlorine or C1-C2 alkyl.

6. Method according to claim 5, characterized in that R1 is H; R2 is isopropyl or tert-butyl; R3 is chlorine; and R4 is methyl. Petition 870250084693, dated 09 / 19 / 2025, page 49 / 141 5 / 9 7. Method according to claim 1 or 2, characterized in that the compound of Formula 3 is prepared from the compound of Formula 5 in a single step without isolating the compound of Formula 4.

8. Method according to claim 2 or claim 3, characterized in that, in step d, the compound of Formula 3 is converted in situ into a compound of Formula 3A in the presence of a suitable acid chloride and a suitable solvent (C). Formula 3 9. Method according to claim 2 or claim 3, characterized in that, in step d, the compound of formula 3 is converted into a compound of formula 3A in the presence of a suitable acid chloride and a suitable solvent (C), wherein the acid chloride of formula 3A can be isolated. Formula 3 Formula 3A 10. Method for preparing a compound of Formula 4, characterized in that the method comprises the step of (step b): reacting a compound of Formula 5 with a compound of Formula 10 in the presence of a suitable base (I), a suitable solvent (B) and an optional phase transfer catalyst to obtain a compound of Formula 4, wherein the compound of Formula 4 is optionally isolated. Petition 870250084693, dated 19 / 09 / 2025, p. 50 / 141 6 / 9 Formula 10 η = 0-2 11. Method, according to any of the preceding claims, characterized in that n = 2.

12. Method, according to any of the preceding claims, characterized in that the suitable base (I), base (II) or base (III) are selected independently from among an inorganic or organic base.

13. Method according to claim 12, characterized in that the inorganic base can be selected from lithium hydrogen carbonate (LiHCOs), sodium hydrogen carbonate (NaHCOs), potassium hydrogen carbonate (KHCO3), cesium hydrogen carbonate (CsHCOs), sodium carbonate (Na2COs), calcium carbonate (CaCOs), cesium carbonate (CS2CO3), lithium carbonate (Li2CO3), potassium carbonate (K2CO3), lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), cesium hydroxide (CsOH), calcium hydroxide (Ca(OH)2), sodium diphosphate (N32HPO4), sodium phosphate (NasPO4), potassium diphosphate (K2HPO4), potassium phosphate (K3PO4), sodium fluoride (NaF), potassium fluoride (KF), fluoride of Cesium (CsF), lithium hydride (LiH), sodium hydride (NaH), potassium hydride (KH), sodium methoxide (NaOCHs), sodium ethoxide (NaOCH2CH3), sodium tert-butoxide or potassium tert-butoxide.

14. Method according to claim 12, characterized in that the organic base can be selected from ethylamine, triethylamine, isopropylamine, di-isopropylamine, tri-isopropylamine, pyridine, picoline, piperidine, methylmorpholine, N-methylpiperidine, A / ,A / -(dimethylamino)pyridine (DMAP), lutidine, colidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), 2,3,4,6,7,8,9,10-octa Petition 870250084693, dated 09 / 19 / 2025, p. 51 / 141 7 / 9 hydropyrimido-[1,2-a]azepine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5diazabicyclo[4.3.0]non-5-ene (DBN) or 1,4-diazabicyclo[2.2.2]octane (DABCO).

15. Method according to any one of claims 1-4 and 8-10, characterized in that suitable solvent (A), solvent (B), solvent (C) or solvent (D) are independently selected from acetonitrile, acetic acid, acetone, hexane, heptane, octane, nonane, decane, dodecane, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, dimethylformamide, ethylene dichloride, ethyl acetate, toluene, xylene, mesitylene, benzene, halogenated benzene, diisopropyl ether, tert-butylmethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, monoglyceride, diglylene, methoxymethane, methoxyethane, ethoxyethane, dimethoxyethane, diethoxyethane, dichloromethane, chloroform, dichloroethane, N,N-dimethylmethanamide, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, hexamethylphosphoramide, 1,3-dimethyl-2-imidazolidinone, or combinations thereof.

16. Method, according to any one of claims 1-4 and 8-10, characterized in that the steps of said method, step-a, step-b, step-c and step-d, are carried out at a temperature in a range of 0 to 150 °C.

17. Method according to claim 1 or claim 2, characterized in that i. the suitable reagent in step a is selected from nitric acid (HNO3), sulfuric acid, acetic acid, hydrochloric acid or mixtures thereof; ii. the suitable solvent (A) in step a is selected from dichloromethane, dichloroethane or acetonitrile; iii. step a is carried out at a temperature in the range of 0 to 100 °C.

18. Method according to claim 1 or claim 2 or claim 10, characterized in that Petition 870250084693, dated 09 / 19 / 2025, page 52 / 141 8 / 9 i. the suitable base (I) in step-b is selected from K2CO3, Na2CO3, NaOH, KOH or K3PO4; ii. the suitable solvent (B) in step-b is selected from dichloroethane, toluene, xylenes, chlorinated benzene, acetonitrile, dioxane and dimethoxyethane; iii. the optional phase transfer catalyst is selected from tetraalkylammonium halide; iv. step-b is carried out at a temperature in a range of 25 to 130 °C.

19. Method according to claim 1 or claim 2, characterized in that i. the hydrolyzing agent in step c is selected from an acid; ii. the suitable solvent in step c is selected from acetic acid (AcOH), water or acetonitrile; iii. step c is carried out within a temperature range of 50 to 130 °C.

20. Method according to any one of claims 2-4 and 8-9, characterized in that i. the acid chloride in step-d is selected from thionyl chloride (SOCl2), mesityl chloride (MsCl), phosphorus pentachloride (PCls), phosphorus trichloride (PCl3), oxalyl chloride, triphosgene or phosgene; ii. the suitable solvent (C) and solvent (D) in step-d are independently selected from dichloroethane, acetonitrile (ACN), N,N-dimethylformamide (DMF), ethyl acetate, pyridine, picoline or mixtures thereof; iii.The suitable base (II) and base (III) in step-d are selected independently from among alkali or alkaline earth metal carbonate, bicarbonate, hydroxide, hydrides or alkoxide, isopropyl amine, triethylamine, diisopropyl ethyl amine, triisopropyl amine, pyridine, picoline, N-methylmorpholine, N-methylpiperidine, N,N-(dimethylamino)pyridine (DMAP), lutidine, colidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4 Petition 870250084693, dated 19 / 09 / 2025, page. 53 / 141 9 / 9 diazabicyclo[2.2.2]octane (DABCO), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN); iv. step-d is carried out at a temperature within a range of 0 to 80 °C. Petition 870250084693, dated 19 / 09 / 2025, p. 54 / 141.