A method for preparing 1-alkyl-1h-1,2,4-traizol-3-amine compounds

Abstract

The present invention relates to a process for preparing a compound of Formula (I) by reacting a compound of Formula (V) and a compound of Formula (VI) to form a compound of Formula (IV) followed by hydrogenation of the compound of Formula (IV) to a compound of Formula (III) and 5 cyclization of the compound of Formula (III) with a reactive compound of Formula (II), to obtain the compound of Formula (I). wherein R1, R2, R3 and LG are as described herein.

Description

[0001]PI External Title: A METHOD FOR PREPARING 1-ALKYL-1H-1,2,4-TRAIZOL-3-AMINE COMPOUNDS FIELD OF THE INVENTION: The present invention relates to a process for the preparation of a compound of Formula (I), its N-oxides 5 or salts thereof. More preferably, the present invention relates to a process for preparing 1-alkyl-1H- 1,2,4-triazol-3-amine compounds wherein R1, R2and R3are as defined herein. BACKGROUND OF THE INVENTION 10 1, 2, 4-Triazole based systemic pesticides have been widely used to prevent fungal diseases in agricultural products for protecting vegetables, fruits and crops. The most commonly used triazole based plant protection fungicides are azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazolediniconazole, epoxyconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, iminenconazole, ipconazole, metconazole, myclobutanil, penconazole, 15 propiconazole, simeconazole, prothioconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, mefentrifluconazole. The fungicidal activity of these triazole compounds is due to the direct inhibition of lanosterol-14-alpha-demethylase activity of CYP51 enzyme in fungi and thereby to inhibit the biosynthesis of ergosterol, which is an essential component of fungal membranes. 3-Amino-1, 2, 4-triazole (Amitrole) is a systemic non-selective herbicide that has been widely used to 20 control a wide range of perennial grasses and broad-leaved weeds. EP0245058A3, EP0303114A2, WO 1991010660A1, JP 02174777, EP0364141, EP 0336354, EP 0393999, EP 0385775, WO 9506049, EP 0555770, DE 3826609, EP 0313311, EP 0342569, EP 0342568 and WO 2022123502A disclose various sulfonyl urea compounds which include 1-alkyl-1H- 1,2,4-triazol-3-amine moiety, as plant growth regulators and herbicides. 25 Additionally, 3-amino-1H-1,2,4-triazoles and compounds comprising 3-amino-1H-1,2,4-triazoles have also been used as pharmaceuticals for treating or preventing various diseases and disorders including cancer. PI External WO 2010 / 052199 discloses compounds that have 3-amino-1H-1,2,4-triazoles, as gamma secretase modulator for the manufacture of medicaments for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, and hereditary cerebral hemorrhage with amyloidosis. WO 2012 / 054366 describes the uses of 3-amino-1H-1,2,4-triazole compounds as medicaments for the 5 treatment of a disorder selected from psychotic disorders, delusional disorders and drug induced psychosis; anxiety disorders, movement disorders, mood disorders, and neurodegenerative disorders. WO 2017018119 describes a composition which comprises 3-amino-1H-1,2,4-triazole as an active ingredient for treating epilepsy. WO 2008058995 describes a compound containing 3-amino-1H-1,2,4-triazole moiety for 10 therapeutically and / or preventively treating diseases and pathological conditions linked to regulation of the insulin and / or insulin-like growth factor (IGF) signaling pathway. US 20050113283A1 discloses 3-amino-1,2,4-triazole compounds as modulators for modulating an Edg-4 receptor mediated biological activity for cancer treatment. Therefore, due to the increased herbicidal or fungicidal or insecticidal activities and pharmaceutical15 significance associated with the 1,2,4-triazol-3-amine compounds or the compounds containing 1,2,4- triazol-3-amine, several methods have been disclosed in the literature for the synthesis of 1,2,4- triazoles, particularly 3-amino-1H-1,2,4-triazole and its N1-alkylated derivatives. Satoshi Ueda (J. Am. Chem. Soc., 2009, 131, 15080–15081) describes a synthesis of 1H-1,2,4- triazoles from amidines and nitriles using Cs2CO3 as a base and molecular oxygen as an oxidant in the 20 presence of CuBr. Zhengkai Chen et al (Org. Lett. 2016, 18, 1334−1337) discloses a metal-free mediated synthesis of 1,3,5-trisubstituted-1,2,4-triazoles from hydrazones and aliphatic amines under aerobic oxidative conditions wherein the reaction proceeds through a cascade C−H functionalization, double C−N bonds 25 formation, and oxidative aromatization sequence as shown below. PI External However, the aforementioned prior art methods were limited to 3-phenyl-1H-1,2,4-triazoles or 3- methyl-1H-1,2,4-triazoles and do not include a method for obtaining 3-amino-1H-1,2,4-triazoles. Further, the prior art methods use additional reagents such as base, oxidant, or a transition metal 5 catalyst during the cyclization of amidines or hydrazones respectively to 1,2,4-triazoles. Kristinsson et al. (Helvetica Chimica Acta (1983), 1129-1133) discloses a method to prepare 1, 5- dimethyl-1H-1,2,4-triazol-3-amine by reacting methylhydrazine with ethyl N-cyanoethanimidothioate in chloroform as shown below. 10 Reiter et al. (Journal of Heterocyclic Chemistry (1986), 401-408) discloses a method to prepare 1- methyl-1H-1,2,4-triazol-3,5-diamine by reacting methylhydrazine with N-cyano-S-methylisothiourea in 1-butanol as described below. Curtius et al. (Science of Synthesis (2004), 603-639) describes a method to obtain 1,5-dimethyl-1H- 15 1,2,4-triazol-3-amine from ethyl N-cyanoethanimidate and methylhydrazine. Nevertheless, the above described prior art processes have disadvantages arising due to the use of methylhydrazine as it is highly corrosive and causes irritation to the skin and eyes, and affects mucous membranes of the respiratory system in humans and also impairs function of the kidneys and liver and 20 thus making them unsafe for commercial scale preparation of 3-amino-1H-1,2,4-triazoles. PI External Hence, there is a need for an improved method for preparing structurally diverse 1-alkyl-1H-1,2,4- triazol-3-amines that is simple, safe, efficient and economically viable that obviates at least one of the shortcomings associated with the known methods. The present invention provides a novel, efficient and cost-effective method which involves safe and 5 readily accessible starting materials, and convenient operating procedures for preparing a compound of Formula (I), its N-oxides or salts thereof, wherein the method is efficient and suitable for commercial scale preparation and also avoids the use of toxic starting materials, additional reagents such as oxidant, base or a transition metal catalyst during cyclization. OBJECTIVE OF THE INVENTION 10 The objective of the present invention is to provide a novel and improved method for preparing a compound of Formula (I), its N-oxides or salts on a commercial scale. The present invention provides a solution to this objective by offering a simple, safe and economically amenable method for preparing a compound of Formula (I), its N-oxides or salts thereof, which comprises cyclization of alkylated aminoguanidine of Formula (III) with an acid or acid derivative of 15 Formula (II) to obtain the compound of Formula (I), its N-oxides or salts thereof, by overcoming at least one of the shortcomings of the process described in the prior art. wherein R1, R2and R3are as described herein. SUMMARY OF THE INVENTION 20 The objective of the present invention is achieved by providing an efficient and commercially viable method for synthesizing a compound of Formula (I), its N-oxides or salts thereof, wherein R1is selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from 25 nitrogen, oxygen and sulfur, PI External wherein said alkyl and haloalkyl groups are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy, C3-C6cycloalkyl or amino; wherein said cycloalkyl, phenyl and the heterocyclic rings are optionally substituted with one or 5 more substituents selected from halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; R2is selected from a group consisting of hydrogen, C1-C6 alkyl and C1-C6 haloalkyl; or R1and R2together may form a 3-6 membered saturated carbocyclic or heterocyclic ring, which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1-C610 haloalkyl, OH, C1-C6 alkoxy, C1-C6 haloalkoxy or amino; and R3is selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein said alkyl and haloalkyl groups are optionally substituted by one or more substituents 15 selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or C3-C6 cycloalkyl; wherein said cycloalkyl, phenyl and the heterocyclic rings are optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy, comprising the steps of: 20 a. reacting an amino guanidine of Formula (V) with a compound of Formula (VI) in a solvent A to obtain a compound of Formula (IV), wherein the compound of Formula (IV) is optionally isolated; 25 b. hydrogenating the compound of Formula (IV) to form a compound of Formula (III) in the presence of a solvent B, wherein the compound of Formula (III) is optionally isolated; and PI External c. cyclizing the compound of Formula (III) with a compound of Formula (II) in a solvent C, to obtain a compound of Formula (I) or its N-oxides or salts thereof, 5 wherein LG is selected from a group consisting of halogen, OH, C1-C6alkoxy and -O-C(O)-R4, wherein R4is selected from C1-C6alkyl, C1-C6haloalkyl or phenyl which is optionally substituted by one or more substituents selected from halogen, C1-C6alkyl and C1-C6alkoxy, and X is an anion selected from halide, carbonate, bicarbonate, nitrate, perchlorate, carboxylate, 10 sulfate, sulfonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, acetate, trifluoroacetate, benzoate, tetrafluoroborate or hexafluorphosphate. The present method also relates to a method for preparing a compound of Formula (I) or its N-oxides or salts, , 15 wherein the method comprising the step of cyclizing the compound of Formula (III) with a compound of Formula (II) in a solvent C, to obtain a compound of Formula (I) or its N-oxides or salts thereof, , PI External wherein R1, R2, R3, R4, LG and X are as described above. DETAILED DESCRIPTION OF THE INVENTION As used herein, the terms “comprises”, “comprising”, “includes”, “including”, or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. 5 For example, 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 process or method. Also, the indefinite articles “a” and “an” preceding an element or component of the present invention are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore “a” or “an” should be read to include one or at least one, and the singular word 10 form of the element or component also includes the plural unless the number is obviously meant to be singular. The compounds of the present disclosure may be present either in pure form or as mixtures of different possible isomeric forms such as stereoisomers or constitutional isomers. The various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, 15 optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers fall within the scope of the claims of the present disclosure. One skilled in the art will appreciate that one stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to the other isomer(s) or when separated from the other isomer(s). Additionally, the person skilled in the art knows processes or methods or technology to separate, enrich, and / or to selectively prepare said 20 isomers. 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 or 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 inorganic or organic base preferably alkali 25 metal or alkaline earth metal salt. The term “halogen” used in the present invention refers to fluoro, chloro, bromo or iodo. The term “C1-C6 alkyl” used in the present invention refers to a linear or branched alkyl with 1 to 6 carbon atoms. Examples of C1-C6 or C1-C4 alkyl includes but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl or n-hexyl and the like. 30 The term “C1-C6 haloalkyl” used in the present invention refers to a linear or a branched alkyl with 1 to 6 carbon atoms, which is substituted with one or more halogen. Examples includes but not limited to PI External chloromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, difluoromethyl, trifluoroethyl, perfluoroethyl and the like. The term “C1-C6alkoxy” used in the present invention refers to a linear or a branched alkoxy with 1 to 6 carbon atoms. Examples includes but not limited to methoxy, ethoxy, isopropoxy, n-butoxy and the 5 like. The term “C1-C6haloalkoxy” used in the present invention refers to a linear or a branched alkoxy with 1 to 6 carbon atoms, which is substituted by one or more halogen. Examples include but not limited to fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, pentafluoroethoxy and the like. 10 The term “C3-C6 cycloalkyl” used in the present invention refers to a 3 to 6-membered saturated non- aromatic carbocyclic ring. Examples include cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl and the like. Unless otherwise specifically mentioned, the term “heterocyclyl” used in the present invention refers to a 4 to 6-membered saturated or unsaturated non-aromatic ring comprising 1 to 4 heteroatoms selected 15 from nitrogen, oxygen or sulfur. The heterocylyl ring can also be in the oxidized form. The term “heteroaryl” used in the present invention refers to a 5 or 6-membered monocyclic heteroaryl ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. Examples of heteroaryl includes but not limited to furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, 20 pyridazinyl, triazinyl, tetrazinyl and the like. In the context of the present invention, the term “optionally” when used in reference to any element, to intermediates, reagents or conditions, including any method step, e.g., the isolation of intermediates; is intended to mean that the subject element is isolated, or alternatively is not isolated from the reaction mixture and directly used for the subsequent chemical reaction. Similarly, this definition is applied in 25 case for reagents or reaction conditions as well. The specification herein and the various features and advantageous details thereof are explained with reference to the non-limiting examples in the description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the 30 specification herein may be practiced and to further enable those of skilled in the art to practice the specification herein. Accordingly, the examples should not be construed as limiting the scope of the specification herein. PI External The description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning 5 and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein. 10 Any discussion of documents, acts, materials, devices, articles and the like that has been included in this specification is solely for the purpose of providing a context for the disclosure. It is not to be taken as an admission that any or all of these matters form a part of the prior art base or were common general knowledge in the field relevant to the disclosure as it existed anywhere before the priority date of this application. 15 Accordingly, the present invention provides a method for preparing a compound of Formula (I) or its N-oxides or salts, wherein R1is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from 20 nitrogen, oxygen and sulfur, wherein said alkyl and haloalkyl groups are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy, C3-C6cycloalkyl or amino; wherein said cycloalkyl, phenyl and the heterocyclic rings are optionally substituted with one or 25 more substituents selected from halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, OH, C1-C6 alkoxy, C1-C6haloalkoxy or amino; R2is selected from a group consisting of hydrogen, C1-C6 alkyl and C1-C6 haloalkyl; or PI External R1and R2together may form a 3-6 membered saturated carbocyclic or heterocyclic ring, which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; and R3is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, 5 phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein said alkyl and haloalkyl groups are optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or C3-C6 cycloalkyl; wherein said cycloalkyl, phenyl and the heterocyclic rings are optionally substituted by one or more 10 substituents selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; comprising the steps of: a. reacting an amino guanidine of Formula (V) with a compound of Formula (VI) in a solvent A to obtain a compound of Formula (IV), wherein the compound of Formula (IV) is optionally isolated; 15 b. hydrogenating the compound of Formula (IV) to form a compound of Formula (III) in the presence of a solvent B, wherein the compound of Formula (III) is optionally isolated; and c. cyclizing the compound of Formula (III) with a compound of Formula (II) in a solvent C, to 20 obtain a compound of Formula (I) or its N-oxides or salts thereof, wherein, PI External LG is selected from a group consisting of halogen, OH, C1-C6alkoxy and -O-C(O)-R4; R4is selected from C1-C6alkyl, C1-C6haloalkyl or phenyl which is optionally substituted by one or more substituents selected from halogen, C1-C6alkyl and C1-C6alkoxy; and X is an anion selected from halide, carbonate, bicarbonate, nitrate, perchlorate, carboxylate, 5 sulfate, sulfonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, acetate, trifluoroacetate, benzoate, tetrafluoroborate, phosphae or hexafluorphosphate. In one embodiment, the intermediate compound of Formula (IV) is subjected directly to hydrogenation step without any isolation, to obtain the compound of Formula (III). In another embodiment, the intermediate compound of Formula (IV) is isolated first and then subjected 10 to hydrogenation to obtain the compound of Formula (III). In one embodiment, the amine compound of Formula (III) is subjected directly to cyclization step without any isolation, to obtain the compound of Formula (I). In another embodiment, the amine compound of Formula (III) is isolated first and then cyclized to obtain the compound of Formula (I). 15 In one embodiment, the step-b is carried out using a metal borohydride such as lithium borohydride, sodium borohydride, sodium triacetoxy borohydride or sodium cyanoborohydride, and in a solvent B, selected from but not limited to water, alcohol, ethers or acids; such as methanol, ethanol, isopropanol, toluene, dichloromethane, tetrahydrofuran, dioxane, t-butyl methyl ether, acetic acid and trifluoroacetic acid or a mixture thereof. 20 In another embodiment, hydrogenation in the step-b is carried out using hydrogen in the presence of a homogenous or a heterogeneous catalyst. In yet another embodiment, hydrogenation in the step-b is carried out using a hydrogen source such as hydrogen gas, formic acid, isopropanol, trichlorosilyl hydride (SiCl3H), phenyldimethylsilyl hydride (SiPhMe2), pinacolborane, triethylamine, a mixture of formic acid and triethylamine, in the presence of 25 a homogenous or heterogenous catalyst. In one embodiment, the cyclization of compound of formula (III) with the compound of formula (II) can be performed in the absence of a base. In another embodiment, the cyclization of compound of formula (III) with the compound of formula (II) can be performed in the presence of a base. PI External In one embodiment the compound of formula (V) is selected from but not limited to aminoguanidine bicarbonate (2582-30-1); aminoguanidinium chloride (1937-19-5); aminoguanidine nitrate (10308-82- 4); aminoguanidine hydrochloride (16139-18-7); hydrazinecarboximidamide, sulfate (1068-42-4); aminoguanidine carbonate (2200-97-7); aminoguanidine hemisulfate (996-19-0); 5 hydrazinecarboximidamide, sulfate (1:1) (2834-84-6); aminoguanidine phosphate (26071-57-8); hydrazinecarboximidamide, conjugate monoacid (58688-90-7); hydrazinecarboximidamide, nitrate (21150-30-1); carbonic acid, compd. with hydrazinecarboximidamide (1:2) (13998-67-9); hydrazinecarboximidamide, dihydrochloride (55457-88-0); hydrazinecarboximidamide, perchlorate (1:1) (41195-24-8); hydrazinecarboximidamide, acetate (1:1) (37598-37-1); formic acid, compd. with 10 hydrazinecarboximidamide (1:1) (104188-36-5); hydrazinecarboximidamide, monohydrobromide (18807-65-3); hydrazinecarboximidamide, ethanedioate (1:1) (1070778-03-8); hydrazinecarboximidamide, phosphate (1:1) (24413-21-6); hydrazinecarboximidamide, methanesulfonate (1:2) (676353-80-3); hydrazinecarboximidamide, methanesulfonate (1:1) (87533-58- 2); hydrazinecarboximidamide, 2,2,2-trifluoroacetate (1:1) (1070777-96-6); 15 hydrazinecarboximidamide, nitrate (1:2) (159024-39-2); hyponitric acid, compd. with hydrazinecarboximidamide (1:2) (90311-89-0); hydrazinecarboximidamide, ethanedioate (51601-65- 1); hydrazinecarboximidamide, monohydriodide (133082-93-6); hydrazinecarboximidamide, phosphate (2:1) (94345-42-3); hydrazinecarboximidamide, sulfate (1:2) (1111225-02-5); hydrazinecarboximidamide, ethanedioae (2:1) (195886-50-1); hydrazinecarboximidamide, conjugate 20 diacid (188539-84-6); benzoic acid, 4-methyl-, compd. with hydrazinecarboximidamide (1:1) (2307749-95-5); hydrazinecarboximidamide, ammonium salt (1:1) (1195372-39-4); acetic acid, 2- hydroxy-, compd. with hydrazinecarboximidamide (1:1) (1070778-17-4); hydrazinecarboximidamide, acetate (146396-83-0); carbonic acid, compd. with hydrazinecarboximidamide (2:1) (10587-01-6); hydrazinecarboximidamide, compd. with 1-methyltrioxide (1:1) (2108288-73-7); 25 In one preferred embodiment, the compound of formula (V) is selected from aminoguanidine bicarbonate; aminoguanidinium chloride; aminoguanidine hydrochloride; or aminoguanidine carbonate. The method of the present invention for preparing the compound of Formula (I), its salts or N-oxides as described above, employed readily available and safe starting materials and reagents, and convenient 30 operating procedures, which make them amenable for commercial scale application and economically convenient method. Additionally, the method described in the present invention does not include any additional reagents such as oxidant, iodine and / or a base or a transition metal catalyst which are normally used in the known methods / processes for obtaining 1,2,4-triazole compounds. With this, the overall cost of the method and the amount of effluent generated during the process can be minimized and thus, the 35 present method is environmentally safe and also has economic benefits. PI External The method of the present invention for preparing the compound of Formula (I), its salt or N-oxides as described herein, uses aminoguanidine which is a very safe and non-toxic reactant that can be used in a large-quantity without leading to any harmful effects to humans and to the environment. The present method further facilitates the simultaneous formation of 1,2,4-triazole and introduction of 5 required R3substituent at the 5thposition of the 1,2,4-triazole ring even in the absence of any additional base and thereby minimizing the waste generated during the process and eventually the overall cost of the process. Further, the present method is used to prepare structurally diverse C5-susbtituted 1-alkyl-1H-1,2,4- triazol-3-amine of Formula (I) through the cyclization of the compound of Formula (III) with the acid 10 derivative R3-C(O)-LG (Formula II), wherein R3is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring. In a one embodiment, R1in Formula (I), Formula (III), Formula (IV) and Formula (VI) is selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, phenyl and a 5 or 6-membered monocyclic heteroaryl ring selected from furanyl, thienyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, 15 isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyrimidinyl, or pyrazinyl, wherein the phenyl and the heteroaryl ring is optionally substituted with one or more substituents selected halogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 alkoxy. Preferably, R1is selected hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, n-pentyl, trifluoromethyl, phenyl, thienyl, thiazolyl, pyrazolyl, pyridyl or pyrimidinyl. More preferably, R1is selected from hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, 20 n-pentyl, trifluoromethyl, phenyl, 2-furanyl, 3-pyrrolyl and 4-pyridyl. In a preferred embodiment, R2in Formula (I), Formula (III), Formula (IV) and Formula (VI) is selected from a group consisting of hydrogen and C1-C2 alkyl and C1-C2 haloalkyl. More preferably, R2is hydrogen, methyl, ethyl and trifluoromethyl. In a preferred embodiment, R3in Formula (I) and Formula (II) is selected from a group consisting of 25 hydrogen, C1-C3 alkyl, C1-C3 haloalkyl and phenyl, wherein the phenyl group is optionally substituted by one or more substituents selected from halogen, C1-C3 alkyl and C1-C3 alkoxy. More preferably, R3is selected from hydrogen, methyl, ethyl, CHF2, CF3, CH2-CF3, CF2-CF3 and phenyl. In a preferred embodiment, LG in Formula (II) is selected from halogen, OH, C1-C3 alkoxy or-O-C(O)- R4, where R4is selected from C1-C2 alkyl, C1-C2 haloalkyl or phenyl. More preferably, LG is selected 30 from chloro, bromo, OH, -OCH3, -O-CH2CH3, -O-CO-CH3, -O-CO-CF3 and -O-CO-Ph. In a preferred embodiment, the Formula (II) is selected from H-COOH, CH3-CO2H, CH3-CH2-COOH, CF3-CO2H, Ph-CO2H, CF3-CF2-CO2H, CF3-CH2-CO2H, CF3-CO-Cl, CF3-CO-OCH2CH3, CF3-CO-O- CO-CF3, CH3-CO-O-CO-CH3and Ph-CO-O-CO-Ph. PI External In a preferred embodiment, the anion X is selected from halide, bicarbonate, carbonate, nitrate, acetate, trifluoroacetate or trifluoromethanesulfonate. More preferably, the anion X is selected from chloride, bicarbonate, carbonate and trifluoroacetate. In a preferred embodiment, the present invention provides the methods for preparing the compound of 5 formula (I), N-oxides or salts thereof as described herein, wherein R1is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, phenyl and a 5 or 6- membered monocyclic heteroaryl ring selected from furanyl, thienyl, thiazolyl, pyrazolyl, pyridyl or pyrimidinyl, wherein the phenyl and the heteroaryl ring is optionally substituted with one or more substituents selected halogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 alkoxy; 10 R2is selected from a group consisting of hydrogen and C1-C2 alkyl and C1-C2 haloalkyl; and R3is selected from a group consisting of hydrogen, C1-C3 alkyl, C1-C3 haloalkyl and phenyl, wherein the phenyl group is optionally substituted by one or more substituents selected from halogen, C1-C3 alkyl and C1-C3 alkoxy. In one embodiment, preferably, LG is selected from halogen, OH, C1-C3 alkoxy or -O-C(O)-R4; 15 R4is selected from C1-C2 alkyl, C1-C2 haloalkyl or phenyl; and X is selected from halide, bicarbonate, carbonate, nitrate, acetate, trifluoroacetate or trifluoromethanesulfonate.In a more preferred embodiment, the method according to the present invention for the preparation of the compound of formula (I), N-oxides or salts thereof as described herein, wherein 20 R1is selected hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, n-pentyl, trifluoromethyl, phenyl, furanyl, thienyl and pyridyl; R2is selected form hydrogen, methyl, ethyl or trifluoromethyl; R3is selected from hydrogen, methyl, ethyl, CF3, CH2-CF3, CF2-CF3 or phenyl. In one preferred embodiment, LG is selected from chloro, bromo, OH, -OCH3, -O-CH2CH3, -O-CO- 25 CH3, -O-CO-CF3 or -O-CO-Ph; and X is selected from chloride, bicarbonate, carbonate or trifluoroacetate. In one embodiment, the solvent A for step-a of the method according to the present invention for the preparation of the compound of Formula (I) as described herein, is selected from but is not limited to polar solvents such as water, methanol, ethanol, isopropanol, acetonitrile, dimethylformamide, and 30 dimethylsulfoxide. Preferably, the solvent in step-a is selected from water, methanol and ethanol, more preferably water. In one embodiment, the suitable reaction temperature to carry out step-a of the method according to the present invention for the preparation of the compound of Formula (I) as described herein, is in the range PI External of 20-100 °C. In a preferred embodiment, the temperature is in the range of 20-70 °C, more preferably, in the range of 20-50 °C and still more preferably 20-25 °C. In a preferred embodiment, the method as described herein, according to the present invention wherein i. solvent A in step-a is selected from water, methanol, ethanol, isopropanol, acetonitrile, 5 dimethylformamide, and dimethylsulfoxide; ii. step-a can be carried out at a temperature ranging from 20-100 °C. The homogeneous or heterogeneous catalyst in step-b of the method according to the present invention for the preparation of the compound of Formula (I) as described herein, can be selected from but not limited to platinum oxide (PtO2), palladium on activated carbon, platinum on carbon, palladium on 10 activated charcoal, palladium on carbon, Raney Nickel, Lindlar catalyst or RhCl(PPh3)3. Preferably, it is selected from platinum oxide (PtO2), 10% palladium on carbon or Raney Nickel. The pressure of hydrogen used for the hydrogenation of the compound of Formula (IV) to the compound of Formula (III) in step-b of the present method, is between 10-50 bar. In a preferred embodiment, it is between 15-25 bar. 15 The amount of the homogeneous or heterogeneous catalyst used in step-b of the method for preparing a compound of Formula (I) as described herein, is between 1-15% w / w. The step-b of the present method according to the present invention for the preparation of the compound of formula I as described herein, can be performed using metal borohydride selected from lithium borohydride, sodium borohydride, sodium triacetoxy borohydride or sodium cyanoborohydride in the 20 presence of a solvent B. The solvent B in step-b of the method according to the present invention for the preparation of the compound of Formula (I) as described herein, is selected from but is not limited to water, alcohol, ether or acid; such as methanol, ethanol, isopropanol, toluene, dichloromethane, tetrahydrofuran, dioxane, t- butyl methyl ether, formic acid, acetic acid and trifluoroacetic acid or a mixture thereof. 25 In a preferred embodiment, the solvent B in step-b of the method according to the present invention for the preparation of the compound of formula (I) as described herein is selected from water and alcohol, such as methanol, ethanol or isopropanol more preferably water. The suitable reaction temperature to carry out step-b of the method for preparing a compound of Formula (I) as described herein, is in the range of 0-90 °C. PI External In a preferred embodiment, suitable reaction temperature to carry out step-b of the method for preparing a compound of Formula (I) as described herein, is in the range of 20-50 °C and more preferably between 40-45 °C. In a preferred embodiment, the step-b of the present method according to the present invention for the 5 preparation of the compound of formula (I) as described herein, wherein i. the homogeneous or the heterogeneous catalyst in step-b is selected from platinum oxide (PtO2), platinum on carbon, palladium on activated carbon, palladium on activated charcoal, palladium on carbon, Raney Nickel, Lindlar catalyst or RhCl(PPh3)3; ii. the solvent B in step-b is selected from water, methanol, ethanol, isopropanol, toluene, 10 dichloromethane, tetrahydrofuran, dioxane, t-butyl methyl ether, formic acid, acetic acid and trifluoroacetic acid or a mixture thereof; iii. the pressure of hydrogen in step-b is between 10-50 bar; iv. the amount of the homogeneous or heterogeneous catalyst is in the range of 1-15% w / w; and v. the suitable reaction temperature in step-b is in the range of 0-90 °C. 15 In a more preferred embodiment, the present invention provides a method for the synthesis of compound of formula (III) comprising the steps of: a. reacting an amino guanidine of Formula (V) with a compound of Formula (VI) to obtain a compound of Formula (IV), wherein the compound of Formula (IV) is optionally isolated; 20 b. hydrogenating the compound of Formula (IV) to form a compound of Formula (III), wherein the compound of Formula (III) is optionally isolated; wherein the solvent used for step-a and step-b is selected from water or alcoholic solvent more preferably water. 25 In one embodiment the alcoholic solvent is selected from methanol, ethanol, or isopropanol. In one embodiment hydrogenation is carried out using Raney nickel catalyst. PI External In one embodiment, the present invention further provides a method for preparing a compound of Formula (I) or its N-oxides or salts, wherein, R1is selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C8 5 cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur; wherein said alkyl and haloalkyl group are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy, C3-C6cycloalkyl or amino; 10 wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; R2is selected from a group consisting of hydrogen, C1-C6alkyl and C1-C6haloalkyl; or R1and R2together may form a 3-6 membered saturated carbocyclic or heterocyclic ring, which is15 optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1- C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; and R3is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur l, 20 wherein said alkyl and haloalkyl are optionally substituted by one or more substituents selected from halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkoxy or C3-C6cycloalkyl; wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted by one or more substituents selected from halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy and C1-C6haloalkoxy; 25 comprising the step of: c. cyclizing a compound of Formula (III) with a compound of Formula (II) in a solvent C, to obtain a compound of Formula (I) or its N-oxides or salts thereof, PI External wherein LG is selected from a group consisting of halogen, OH, C1-C6 alkoxy and -O-C(O)-R4, wherein R4is selected from C1-C6 alkyl, C1-C6 haloalkyl or phenyl which is optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl and C1-C6 alkoxy, 5 and X is an anion selected from halide, bicarbonate, carbonate, nitrate, perchlorate, carboxylate, sulfonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, acetate, trifluoroacetate, benzoate, tetrafluoroborate or hexafluorphosphate. In one embodiment the step-c is carried out in the presence of base. 10 In another embodiment the step-c is carried out in the absence of the base. According to the present invention, the solvent C used for cyclization in step-c of the present methods for preparing a compound of Formula (I) as described herein, is a polar or a non-polar solvent selected from but not limited to dimethylformamide, acetonitrile, tetrahydrofuran, dimethoxyethane, dioxane, tert-butyl methyl ether and toluene. Preferably, the solvent C used for cyclization in step-c is selected 15 from acetonitrile, toluene and dimethylformamide, more preferably acetonitrile and toluene. According to the present invention, the base in step-c of the present methods for preparing a compound of Formula (I) as described herein, if used, is an organic or an inorganic base selected from but not limited to triethylamine, isopropylamine, diisopropylethylamine, pyridine, picoline, alkali or alkaline earth metal carbonate, alkali or alkaline earth metal bicarbonate, alkali or alkaline earth metal hydroxide, 20 alkali or alkaline earth metal hydrides, alkali or alkaline earth metal alkoxide, acetate or benzoate etc. In a preferred embodiment, the base is selected from triethylamine, potassium carbonate, cesium carbonate or sodium carbonate. The suitable reaction temperature in step-c of the present methods for preparing a compound of Formula (I) as described herein, can be varied from -30 - 120 °C. 25 In one embodiment, the step-c of the present invention is performed preferably in the absence of the base. In a preferred embodiment, the present method as described herein, wherein PI External i. the base in step-c, if used, is selected from triethylamine, isopropylamine, diisopropylethylamine, pyridine, picoline, alkali or alkaline earth metal carbonate, alkali or alkaline earth metal bicarbonate, alkali or alkaline earth metal hydroxide, alkali or alkaline earth metal hydrides, alkali or alkaline earth metal alkoxide, acetate or benzoate, preferably it is selected from triethylamine, 5 potassium carbonate, cesium carbonate or sodium carbonate; ii. the solvent C in step-c is selected from dimethylformamide, acetonitrile, tetrahydrofuran, dimethoxyethane, dioxane, tert-butyl methyl ether and toluene; iii. the suitable reaction temperature in step-c can be varied from -30 - 120 °C. The suitable reaction temperature to carry out step-c of the present methods for preparing a compound 10 of Formula (I) as disclosed herein wherein LG is halogen, C1-C6 alkoxy and -O-C(O)-R4in formula II, is in the range of -30 - 120 °C. In a preferred embodiment, it is in the range of -10 - 40 °C and more preferably in the range of -5 - 10 °C. The suitable reaction temperature to carry out step-c of the present methods for preparing a compound of Formula (I) as disclosed herein wherein LG is -OH in formula II, is in the range of -20 - 120 °C. 15 In a preferred embodiment, the addition of acid is at the temperature ranging from 10 - 40 °C, followed by heating at 110 °C. In one embodiment the after completion of reaction in step-a to step-c the pH of the mixture was adjusted in the ranges of 5-8 depending on the substitution. The reaction time is not critical and depends on the batch size, temperature, type of reaction and the 20 reagents used and is usually between few minutes to few hours. The present methods for preparing the compound of formula (I) as described herein, wherein the steps can be carried out in a batch, semi-continuous or continuous reaction mode, specifically also under semi- continuous flow or continuous flow reaction conditions. The person skilled in the art knows the best work-up of the reaction mixtures after the end of the 25 respective reactions. The work-up is usually carried out by isolation of the product, and optionally washing with solvent, and further optionally drying of the product if useful or required. The isolation of the reaction product can be carried out by a technique which includes but is not limited to decantation, filtration, centrifugation, evaporation, liquid-liquid extraction, distillation, recrystallization, chromatography and the like or a combination thereof. 30 The reaction steps according to the invention are generally carried out under atmospheric pressure. Alternatively, however, it is also possible to work the method steps of the present method under reduced pressure or higher pressure. PI External The invention is further illustrated by the following examples which are provided to be exemplary of the invention, and do not limit the scope of the invention. While 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 are intended to be included within the scope of the present invention. 5 Although the subject matter has been described in considerable detail with reference to certain examples and implementations thereof, other implementations are possible. EXPERIMENTAL EXAMPLES: Scheme 1: Preparation of the compound of Formula (I) 10 All the solvents and the reagents used in the present invention are obtained from commercial sources. Reactants such as aminoguanidine hydrochloride (Formula V), ketone compounds of Formula (VI) and compound of formula (II) are obtained from commercial suppliers. EXAMPLE 1: Step-a: Synthesis of Imine compound of Formula (IV) 15 Method: I Aminoguanidine hydrochloride (110 g, 1 mol) was added into a solvent (EtOH or MeOH or H2O, 330 mL) and stirred at 22-24 °C. To this reaction mixture, aldehyde / ketone of Formula (VI) (1 mol) was added over 15-90 minutes at 22-24 °C. The reaction mass was continued to stir for 2-12 h at 22-70 °C. 20 After completion of the reaction, pH was adjusted with aqueous NaOH and the crude reaction mass was taken as such to the next step. Method: II PI External Aminoguanidine bicarbonate (136 g, 1 mol) was added into a solvent (EtOH or MeOH or H2O, 400 mL) followed by conc. hydrochloric acid (1 mol) and stirred at 22-24 °C. To this reaction mixture, aldehyde / ketone of Formula (VI) (1 mol) was added over 15-90 minutes at 22-24 °C. The reaction mass 5 was continued to stir for 2-12 h at 22-70 °C. After completion of the reaction, pH was adjusted with aqueous NaOH and the crude reaction mass was taken as such to the next step. 10 Method-I using PtO2 (1% w / w) The crude reaction mass obtained in step-(a) and PtO2 (1.1 g, 1% w / w) were added into an autoclave. The autoclave was pressurized with 50 kg / cm2hydrogen gas (~50 bar) and heated at 25-30 °C for 24 h. 15 After completion of the reaction, the catalyst was removed by filtration and pH of the filtrate was adjusted to acidic pH with 15% aqueous hydrochloric acid. The reaction mixture was concentrated under reduced pressure. The residue obtained was suspended in isopropanol (330 mL) and heated between 55 to 60 °C under stirring for 60 minutes and gradually cooled to 5 to 10 °C over 60 minutes. The solid obtained was filtered, washed with cold isopropanol (100 mL). The wet cake obtained was 20 dried under reduced pressure to afford pure corresponding amine hydrochloride salt. Method-II using Pd / C (10% w / w) The crude reaction mass obtained in step-a and Pd / C (11.0 g, 10% w / w) were added into an autoclave. The autoclave was pressurized with 50 kg / cm2hydrogen gas (~50 bar) and heated at 25-30 °C for 24 h. 25 After completion of the reaction, the catalyst was removed by filtration and pH of the filtrate was adjusted to 2-3 with 15% aqueous hydrochloric acid. The reaction mixture was concentrated under reduced pressure to afford crude amine hydrochloride salt, which was used in the next step without purification. 30 Method-III using Raney-Ni (15% w / w) PI External The crude reaction mass obtained in step-a and Raney-Ni (16.5 g, 15% w / w) were added into an autoclave. The autoclave was pressurized with 25 kg / cm2hydrogen gas (~25 bar) and heated at 35-40 °C for 4 h. After completion of the reaction, the catalyst was removed by filtration and pH of the filtrate was adjusted to acidic pH using 15% aqueous hydrochloric acid. The reaction mixture was concentrated 5 under reduced pressure. The residue obtained was suspended in isopropanol (330 mL) and heated between 55 to 60 °C under stirring for 60 minutes and gradually cooled to 5 to 10 °C over 60 minutes. The solid was filtered, washed with cold isopropanol (110 mL). The wet cake obtained dried under reduced pressure to afford pure corresponding amine hydrochloride salt. 10 Method-IV using NaBH4 The crude reaction mass obtained in step-a was cooled to 8-10°C. To this, solid NaBH4 or aqueous solution of NaBH4 (1-3 mol) was added over 30-90 minutes. The reaction mixture was then warmed to 22-24°C and stirred for 20 h. After completion of the reaction, the reaction mixture was cooled to 0- 5°C, pH was adjusted to acidic pH using with a 15% aqueous hydrochloric acid. The reaction mixture 15 was concentrated under reduced pressure to obtain the corresponding amine hydrochloride salt as a crude product. Step-c: Synthesis of triazole compound of Formula (I) 20 Method-I (using anhydride reactant) Amine hydrochloride salt (1 mol) obtained in step-b was added into acetonitrile (400 mL) under stirring. The reaction mass was cooled to -10 °C. A solution of corresponding anhydride (1 mol) in acetonitrile (250 mL) was added over 5-120 minutes at -10 to -5 °C. The reaction mixture was stirred for 1-5 h at - 5 to 0°C. After completion of the reaction, pH of the reaction mixture was adjusted with 20% aqueous 25 sodium hydroxide solution. Acetonitrile was distilled out and the pH was adjusted to ~ 10 with 20% aqueous sodium hydroxide solution. The crude reaction mass was stirred at 0 to 5 °C for 60 minutes, the solid was filtered, washed with cold water (150 mL) and dried under reduced pressure to obtain the corresponding substituted triazole compounds, yield over three steps: 60-70%. Method-II (using acid reactant) 30 Amine hydrochloride salt (1 mol) obtained in step-b was added into toluene (500 mL) under stirring. HCOOH or CF3COOH (1.2-2.5 mol) was added over 5-15 minutes at 110 °C for 1-12 h. During this time, water that was generated from the reaction, and the excess acid were collected using a Dean-Stark PI External apparatus. After completion of the reaction, the reaction mixture was cooled to 22-24°C and the pH was adjusted to neutral to basic pH using 20% aqueous sodium hydroxide solution. The organic layer was separated, and the aqueous layer was extracted with toluene, filtered, and dried under reduced pressure to obtain the corresponding substituted triazole compounds, yield over three steps: 60-70%. 5 Method-III (using acid chloride reactant) Triethylamine (1 mol) and the amine hydrochloride salt obtained in step-b (1 mol) were added into acetonitrile (900 mL) under stirring. The reaction mass was cooled to -30 °C followed by the addition of trifluoroacetyl chloride (1 mmol) over 05-120 min. After complete addition, the reaction mixture was warmed to 22-24°C, and stirred further for 30-60 min. After completion of the reaction, the pH of the 10 reaction mixture was adjusted to neutral to basic pH using 10% aqueous sodium hydroxide solution. Acetonitrile was distilled out and pH was adjusted to ~ 10 with 10% aqueous sodium hydroxide solution. The residue was extracted with ethyl acetate, dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain corresponding substituted triazole compounds. Method-IV (using acid ester as a reactant) 15 Acetonitrile (900 mL), followed by ethyl trifluoroacetate (1 mol) and 1-methylamino guanidine (1 mol) obtained in step-b were added into an autoclave and heated at 100°C for 10 h. After completion of the reaction, the pH of the reaction mixture was adjusted with 10% aqueous sodium hydroxide solution. Acetonitrile was distilled out and pH was adjusted to ~ 10 with 10% aqueous sodium hydroxide solution. The residue was extracted with ethyl acetate (300 mL), dried over anhydrous sodium sulphate 20 and concentrated under reduced pressure to obtain substituted triazole compounds. The following compounds are synthesized according to the present process using the general procedure described in Example 1. Table 1: Compounds of Formula (I) synthesized using the present process Sr. Step-c : Structure Analytical Data No. Methods 1H NMR (DMSO-d6, 400MHz): δ 5.75 (s, 2H), 3.76 (s, 3H), 13C NMR (DMSO-d6, 100MHz): δ 162.9,141.1-140.0 (q), I, II, III 1 122.1-114.1 (q), 36.0 and IV19F NMR (DMSO-d6, 377MHz): δ -61.59 LCMS: 167.1 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 5.76 (s, 2H), 4.10 (q, 2H), 1.31 (t, J = 7.4 Hz, 3H) 13C NMR (DMSO-d6, 100MHz): δ163.1, 140.6-139.4 (q), 2 I 122.2-114.1 (q), 44.2, 14.9 19F NMR (DMSO-d6, 377MHz): δ -61.47 LCMS: 181.1 [M+H]+ PI External 1H NMR (DMSO-d6, 400MHz): δ 5.77 (s, 2H), 4.03 (t, J=7.0 Hz, 2H), 1.74-1.67 (m, 2H), 1.28-1.19 (m, 2H), 0.85 (t, J=7.4 Hz, 3H) 3 I13C NMR (DMSO-d6, 100MHz): δ 163.6, 141.5-140.3 (q), 122.7-114.7 (q), 49.2, 31.6, 19.4, 13.8 19F NMR (DMSO-d6, 377MHz): δ -61.03 LCMS: 195.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 5.75 (s, 2H), 3.84 (d, J=8.0 Hz, 2H), 2.16-2.07 (m, 1H), 0.83 (d, J=8.0 Hz, 6H) 13C NMR (DMSO-d6, 100MHz): δ 163.1, 141.4-140.2 (q), 4 I 122.2-114.1 (q), 55.7, 28.3, 19.2, 19.2 19F NMR (DMSO-d6, 377MHz): δ -60.49 LCMS: 209.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 7.37-7.28 (m, 3H), 7.23- 7.21 (m, 2H), 5.90 (s, 2H), 5.29 (s, 2H) 13C NMR (DMSO-d6, 100MHz): δ 163.4, 141.3-140.2 (q), 5 I, II 135.5, 128.7, 128.7, 128.1, 127.3, 127.3, 122.2-114.1 (q), 52.4 19F NMR (DMSO-d6, 377MHz): δ -60.91 LCMS: 243.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 8.58-8.52 (m, 2H), 7.16 (d, J=4.4 Hz, 2H), 5.95 (s, 2H), 5.38 (s, 2H) 13C NMR (DMSO-d6, 100MHz): δ 163.5, 150.0, 149.7, 6 I 144.4, 141.8-140.7 (q), 122.1, 121.8, 121.5-114.0 (q), 51.2 19F NMR (DMSO-d6, 377MHz): δ -61.13 LCMS: 244.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 5.78 (s, 2H), 4.57-4.47 (m, 1H), 1.37 (d, J=6.4 Hz, 6H) 13C NMR (DMSO-d6, 100MHz): δ 163.0, 140.1-138.9 (q), 7 I 122.3-114.2 (q), 51.2, 22.1, 22.1 19F NMR (DMSO-d6, 377MHz): δ -61.30 LCMS: 195.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 5.00 (s, 2H), 3.48 (s, 3H), 2.17 (s, 3H) 8 I13C NMR (DMSO-d6, 100MHz): δ 162.1, 150.2, 34.0, 11.1 LCMS: 113.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 7.86 (s, 1H), 5.22 (s, 2H), 3.54 (s, 3H) 9 I13C NMR (DMSO-d6, 100MHz): δ 164.1, 142.8, 35.1 LCMS: 99.2 [M+H]+1H NMR (DMSO-d6, 400MHz): 5.81 (s, 2H), 3.79 (s, 3H) 13C NMR (DMSO-d6, 100MHz): δ 163.4, 159.0-158.3 (t), 10 II 139.4-138.8 (t), 123.6-104.2 (m), 36.5 19F NMR (DMSO-d6, 377MHz): δ -82.69, -111.55 LCMS: 217.1 [M+H]+ PI External 1H NMR (DMSO-d6, 400MHz): δ 7.28 (t, J=52.4 Hz, 1H), 5.49 (s, 2H), 3.70 (s, 3H) 13C NMR (DMSO-d6, 100MHz): δ 163.1, 145.5-144.9 (t), 11 I 110.1-105.4 (t), 35.1 19F NMR (DMSO-d6, 377MHz): δ -116.73, -116.87 LCMS: 149.2 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 5.72 (s, 2H), 3.76 (s, 3H) 13C NMR (DMSO-d6, 100MHz): δ 162.5, 144.7-144.1 (t), 12 I 122.4-116.7 (t), 36.2 19F NMR (DMSO-d6, 377MHz): δ -49.80 LCMS: 183.1 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 7.63 (t, J=1.0 Hz, 1H), 6.46-6.42 (m, 2H), 5.82 (s, 2H), 5.29 (s, 2H) 13C NMR (DMSO-d6, 100MHz): δ 163.1, 147.9, 13 I 143.5,140.8-140.4(d), 119.4-114.0 (t), 110.7, 109.6, 45.6 19F NMR (DMSO-d6, 377MHz): δ -60.77 LCMS: 232.9 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 3.87 (bs, 2H), 3.60 (s, 3H), 2.61 (q, 2H), 1.28 (t, J=7.6 Hz, 3H) 14 I13C NMR (DMSO-d6, 100MHz): δ 161.5, 155.9, 34.2, 19.1, 11.6 LCMS: 127.1 [M+H]+1H NMR (DMSO-d6, 400MHz): δ 5.77 (s, 2H), 4.03 (t, J=7.0 Hz, 2H), 1.74-1.67 (m, 2H), 1.28-1.19 (m, 2H), 0.85 (t, J=7.4 Hz, 3H); 15 I13C NMR (DMSO-d6, 100MHz): δ 163.6, 141.5-140.3 (q), 122.7-114.7 (q), 49.2, 31.6, 19.4, 13.8 19F NMR (DMSO-d6, 377MHz): δ -61.03 LCMS:209.2 [M+H]+Having described the invention with reference to certain preferred embodiments, other embodiments will become apparent to one skilled in the art from consideration of the specification.

Claims

PI External CLAIMS:

1. A method for preparing a compound of Formula (I) or its N-oxides or salts,wherein, R1is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C85 cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein said alkyl and haloalkyl group are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy, C3-C6cycloalkyl or amino; 10 wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; R2is selected from a group consisting of hydrogen, C1-C6alkyl and C1-C6haloalkyl; or R1and R2together may form a 3-6 membered saturated carbocyclic or heterocyclic ring, which is15 optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1- C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; and R3is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur l, 20 wherein said alkyl and haloalkyl are optionally substituted by one or more substituents selected from halogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkoxy or C3-C6cycloalkyl; wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted by one or more substituents selected from halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy and C1-C6haloalkoxy, 25 comprising the steps of:PI External a. reacting an amino guanidine of Formula (V) with a compound of Formula (VI) in a solvent A to obtain a compound of Formula IV, wherein the compound of Formula (VI) is optionally isolated;5 b. hydrogenating the compound of Formula (IV) to form a compound of Formula (III) in the presence of a solvent B, wherein the compound of Formula (III) is optionally isolated; andc. cyclizing the compound of Formula (III) with a compound of Formula (II) in a solvent C to obtain a compound of Formula (I) or its N-oxides or salts thereof,10 wherein LG is selected from a group consisting of halogen, OH, C1-C6alkoxy and -O-C(O)-R4, wherein R4is selected from C1-C6alkyl, C1-C6haloalkyl or phenyl which is optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl and C1-C6 alkoxy, and 15 X is an anion selected from halide, bicarbonate, nitrate, perchlorate, carboxylate, sulfonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, acetate, trifluoroacetate, benzoate, tetrafluoroborate or hexafluorphosphate.

2. A method for preparing a compound of Formula (I) or its N-oxides or salts,PI External wherein, R1is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, C3-C8cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, wherein said alkyl and haloalkyl group are optionally substituted with one or more substituents 5 selected from halogen, cyano, C1-C6alkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy, C3-C6cycloalkyl or amino; wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; 10 R2is selected from a group consisting of hydrogen, C1-C6 alkyl and C1-C6 haloalkyl; or R1and R2together may form a 3-6 membered saturated carbocyclic or heterocyclic ring, which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C6 alkyl, C1- C6 haloalkyl, OH, C1-C6 alkoxy, C1-C6 haloalkoxy or amino; and R3is selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 15 phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur l, wherein said alkyl and haloalkyl are optionally substituted by one or more substituents selected from halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy or C3-C6 cycloalkyl; wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted by one or 20 more substituents selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy and C1-C6 haloalkoxy, comprising the step of: c. cyclizing a compound of Formula (III) with a compound of Formula (II) in a solvent C to obtain a compound of Formula (I) or its N-oxides or salts thereof, 25 wherein LG is selected from a group consisting of halogen, OH, C1-C6 alkoxy and -O-C(O)-R4, wherein R4is selected from C1-C6alkyl, C1-C6haloalkyl or phenyl which is optionally substituted by one or more substituents selected from halogen, C1-C6alkyl and C1-C6alkoxy, andPI External X is an anion selected from halide, bicarbonate, carbonate, nitrate, perchlorate, carboxylate, sulfonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, acetate, trifluoroacetate, benzoate, tetrafluoroborate or hexafluorphosphate.

3. A method for the synthesis of compound of formula (III) comprising the steps of: 5 a. reacting an amino guanidine of Formula (V) with a compound of Formula (VI) in a solvent A to obtain a compound of Formula IV, wherein the compound of Formula (VI) is optionally isolated;b. hydrogenating the compound of Formula (IV) to form a compound of Formula (III) in the 10 presence of a solvent B, wherein the compound of Formula (III) is optionally isolated;wherein, R1is selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3- C8 cycloalkyl, phenyl and a 4 to 6-membered heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, 15 wherein said alkyl and haloalkyl group are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6 alkyl, OH, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 cycloalkyl or amino; wherein said cycloalkyl, phenyl and the heterocyclic ring are optionally substituted with one or more substituents selected from halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, OH, C1-C6 20 alkoxy, C1-C6 haloalkoxy or amino; R2is selected from a group consisting of hydrogen, C1-C6alkyl and C1-C6haloalkyl; or R1and R2together may form a 3-6 membered saturated carbocyclic or heterocyclic ring, which is optionally substituted with one or more substituents selected from halogen, cyano, C1-C6alkyl, C1-C6haloalkyl, OH, C1-C6alkoxy, C1-C6haloalkoxy or amino; and 25 X is an anion selected from halide, bicarbonate, carbonate, nitrate, perchlorate, carboxylate, sulfonate, methanesulfonate, trifluoromethanesulfonate, p-toluenesulfonate, acetate, trifluoroacetate, benzoate, tetrafluoroborate or hexafluorphosphate.

4. The process as claimed in claim 1, 2 or claim 3, whereinPI External R1is selected from a group consisting of hydrogen, C1-C6alkyl, C1-C6haloalkyl, phenyl and a 5 or 6-membered monocyclic heteroaryl ring selected from furanyl, pyrrolyl, pyrazolyl or pyridyl, wherein the phenyl and the heteroaryl ring is optionally substituted with one or more substituents selected halogen, C1-C6alkyl, C1-C6haloalkyl, and C1-C6alkoxy; 5 R2is selected from a group consisting of hydrogen and C1-C2alkyl and C1-C2haloalkyl; R3is selected from a group consisting of hydrogen, C1-C3alkyl, C1-C3haloalkyl and phenyl, wherein the phenyl group is optionally substituted by one or more substituents selected from halogen, C1-C3alkyl and C1-C3alkoxy; LG is selected from halogen, OH, C1-C3 alkoxy or-O-C(O)-R4; 10 R4is selected from C1-C2 alkyl, C1-C2 haloalkyl or phenyl; and X is selected from halide, bicarbonate, carbonate, nitrate, acetate, trifluoroacetate or trifluoromethanesulfonate.

5. The process as claimed in claim 1, 2 or claim 3, wherein R1is selected hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, n-pentyl, trifluoromethyl, 15 phenyl, furanyl, pyrrolyl and pyridyl; R2is hydrogen, methyl, ethyl and trifluoromethyl; R3is selected from hydrogen, methyl, ethyl, CF3, CH2-CF3, CF2-CF3 and phenyl; LG is selected from chloro, bromo, OH, -OCH3, -O-CH2CH3, -O-CO-CH3, -O-CO-CF3 and - O-CO-Ph; and 20 X is selected from chloride, bicarbonate, carbonate and trifluoroacetate.

6. The method as claimed in claim 1 or 3, wherein step-b is carried out using hydrogen in the presence of a homogeneous or a heterogeneous catalyst and a solvent B.

7. The process as claimed in claim 3 or 6, wherein the hydrogenation is carried out using Raney nickel catalyst. 25 8. The method as claimed in claim 1 or 3, wherein step-b is carried out using a metal borohydride selected from lithium borohydride, sodium borohydride, sodium triacetoxy borohydride or sodium cyanoborohydride in the presence of a solvent B.

9. The method as claimed in claim 1 or 3, wherein solvent B is selected from water, methanol, ethanol, isopropanol, toluene, dichloromethane, tetrahydrofuran, dioxane, t-butyl methyl ether, 30 acetic acid and trifluoroacetic acid or a mixture thereof.

10. The method as claimed in claim 1 or 2, wherein step-c is performed without a base.

11. The method as claimed in claim 1 or 3, whereinPI External i. solvent A in step-a is selected from water, methanol, ethanol, isopropanol, acetonitrile, dimethylformamide, and dimethylsulfoxide; ii. step-a is carried out at a temperature ranging from 20-100 °C.

12. The method as claimed in claim 1, or claim 3, wherein 5 i. the homogeneous or the heterogeneous catalyst in step-b is selected from platinum oxide (PtO2), platinum on carbon, palladium on activated carbon, palladium on activated charcoal, palladium on carbon, Raney Nickel, Lindlar catalyst or RhCl(PPh3)3; ii. the solvent B in step b is selected from water, methanol, ethanol, isopropanol, toluene, 10 dichloromethane, tetrahydrofuran, dioxane, t-butyl methyl ether, acetic acid and trifluoroacetic acid or a mixture thereof; iii. the pressure of hydrogen in step-b is between 10-50 bar; iv. the amount of the homogeneous or heterogeneous catalyst is in the range of 1-15% w / w; and 15 v. the suitable reaction temperature in step-b is in the range of 0-90 °C.

13. The method as claimed in claim 1 or 3, wherein the said solvent A and solvent B is selected form water, alcoholic solvent or mixture thereof.

14. The method as claimed in claim 1, or claim 2, wherein i. the base in step-c, if used, is selected from triethylamine, isopropylamine, 20 diisopropylethylamine, pyridine, picoline, alkali or alkaline earth metal carbonate, alkali or alkaline earth metal bicarbonate, alkali or alkaline earth metal hydroxide, alkali or alkaline earth metal hydrides, alkali or alkaline earth metal alkoxide, acetate or benzoate, preferably it is selected from triethylamine, potassium carbonate, cesium carbonate or sodium carbonate; 25 ii. the solvent C in step-c is selected from dimethylformamide, acetonitrile, tetrahydrofuran, dimethoxyethane, dioxane, tert-butyl methyl ether and toluene; iii. the suitable reaction temperature in step-c can be varied from -30 - 120 °C.

15. The method as claimed in claim 2, wherein i. the solvent C in step-c is selected from dimethylformamide, acetonitrile, 30 tetrahydrofuran, dimethoxyethane, dioxane, tert-butyl methyl ether and toluene; and ii. the suitable reaction temperature in step-c can be varied from -30 - 120 °C.

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