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Title:
PROCESS FOR PREPARATION OF AZABICYCLO [3.1.0] HEXANE INTERMEDIATES
Document Type and Number:
WIPO Patent Application WO/2023/175526
Kind Code:
A1
Abstract:
The present invention generally relates to a process for preparation of azabicyclo [3.1.0] hexane intermediate of Formula (I), an intermediate for preparation of certain antiviral compounds for example boceprevir and nirmatrelvir. Wherein "R1" is selected from hydrogen, alkyl, aryl or aralkyl.

Inventors:
MEKALA NAGA RAJU (IN)
LAGADAPATI SRINIVASA RAO (IN)
KOLA LAKSHMI KANTH (IN)
SHAIK FIROZ (IN)
BASINENI PEDDA REDDAIAH (IN)
BARIK PRASANT KUMAR (IN)
GALLA TIRUMALA RAO (IN)
NADELLA MADHU MURTHY (IN)
SIMHADRI SRINIVAS (IN)
VASIREDDI UMA MAHESWER RAO (IN)
Application Number:
PCT/IB2023/052509
Publication Date:
September 21, 2023
Filing Date:
March 15, 2023
Export Citation:
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Assignee:
LAURUS LABS LTD (IN)
International Classes:
C07C215/20; C07C69/74; C07C233/58; C07D209/54
Domestic Patent References:
WO2004113295A12004-12-29
WO2007075790A12007-07-05
Foreign References:
CN104163759A2014-11-26
Download PDF:
Claims:
WE CLAIM: 1. A process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, b) reacting the compound of Formula III or a salt thereof with benzyl amine to obtain a compound of Formula IV or a salt thereof, and c) cyclizing the compound of Formula IV or a salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V. 2. The process as claimed in claim 1, wherein R represents methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert butyl, bromo, chloro or Iodo. 3. The process as claimed in claim 1, wherein the suitable oxidizing agent is selected from the group comprising bromine, hydrogen peroxide, Potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate, sodium monopersulfate, potassium permanganate, sodium permanganate and mixture thereof.

4. The process as claimed in claim 1, wherein the compound of Formula II is a compound formula IIa 5. The process as claimed in claim 1, wherein the oxidizing agent is potassium permanganate. 6. The process as claimed in claim 1, wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. 7. The process as claimed in claim 1, wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity in a sequential manner one after another. 8. The process as claimed in claim 1, wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity in a sequential manner one after another at a temperature of about 20°C to about 30°C. 9. The process as claimed in claim 6, wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 4 to about 5 equal parts of the total quantity. 10. The process as claimed in claim 1, wherein the step a) reaction is carried out at a temperature of about 35°C to about 40°C. 11. The process as claimed in claim 1, wherein the step a) is carried out in presence of a base and a solvent. 12. The process as claimed in claim 11, wherein the base is selected from sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium-butoxide, potassium hydroxide, potassium carbonate, potassium bicarbonate, triethyl amine, diisopropyl ethyl amine and mixtures thereof; and wherein the solvent is selected from tetrahydrofuran, dimethyl ether, isopropyl ether, methyl tertiary butyl ether, 1,4-dioxane; ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate; ketones include but are not limited to acetone, methyl ethyl ketone, methyl isobutyl ketone; halogenated hydrocarbons include, but are not limited to methylene chloride, ethylene chloride, chloroform; aprotic organic solvent, include but are not limited to N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, l,3-dimethyl-2-imidazolidinone, acetonitrile; water and mixture thereof. 13. The process as claimed in claim 12, wherein the base is sodium hydroxide and the solvent is water. 14. The process as claimed in claim 1, wherein the suitable cyclizing agent is selected from the group comprising acetic anhydride, sulfuric acid, para toluene sulfonic acid and mixture thereof. 15. The process as claimed in claim 1, wherein the step b) is carried out in a suitable solvent; wherein the suitable solvent is selected from the group comprising dimethylacetamide, dimethylformamide, N- methylpyrrolidone, dimethyl sulfoxide, diethyl sulfoxide, toluene, xylene and mixture thereof. 16. The process as claimed in claim 1, wherein the suitable cyclizing agent is acetic anhydride. 17. The process as claimed in claim 1, wherein the step b) and step c) are carried out at a temperature of about 135°C to about 145°C. 18. The process as claimed in claim 1, wherein the steps a) to c) are carried out in one- pot reaction. 19. A process for preparation of compound of Formula V, comprising: Formula V a) reacting a compound of Formula III or salt thereof with benzamine to obtain a compound of Formula IV or salt thereof, and b) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain a compound of Formula V. 20. The process as claimed in claim 19, wherein the suitable cyclizing agent is selected from the group comprising acetic anhydride, sulfuric acid, para toluene sulfonic acid and mixture thereof. 21. The process as claimed in claim 19, wherein the step a) is carried out in a suitable solvent; wherein the suitable solvent is selected from the group comprising dimethylacetamide, dimethylformamide, N- methylpyrrolidone, dimethyl sulfoxide, diethyl sulfoxide, toluene, xylene and mixture thereof. 22. The process as claimed in claim 20, wherein the cyclizing agent is acetic anhydride. 23. The process as claimed in claim 21, wherein the solvent is xylene. 24. The process as claimed in claim 19, wherein the steps a) and b) are carried out in one-pot reaction. 25. The process as claimed in claim 19, wherein the step a) and step b) are carried out at a temperature of about 135°C to about 145°C. 26. A process for preparation of caronic amide of Formula VI or a salt thereof, comprising: reacting a caronic acid of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI. 27. The process as claimed in claim 26, wherein the suitable source of amine is selected from the group comprising urea, ammonia, formamide and mixtures thereof. 28. The process as claimed in claim 26, wherein the reaction is carried out in presence of a suitable catalyst selected from the group comprising 1,8- Diazabicyclo[5.4.0]undec-7-ene, triethylamine, trimethylamine, dimethylamine, diethylamine, dibenzoyl peroxide, toluene-4-sulfonic acid, hydrogen peroxide, pyridine, dimethylaminopyridine, acetic acid, tetrabutyl ammonium bromide, azobisisobutyronitrile, copper(I)/DBU catalyst, copper(II) acetate, copper(I) bromide, iron(III) acetylacetonate, ruthenium based catalysts, molecular sieves, tetra methyl guanidine, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene, triazabicyclo[4.4.0]dec-5-ene, 1,5-diazabicyclo[4.3.0] non-5-ene, proton sponge, 1,4-diazabicyclo[2.2.2]octane/tri ethylene diamine and mixture thereof. 29. The process as claimed in claim 28, wherein the suitable catalyst is 1,8- Diazabicyclo[5.4.0]undec-7-ene, triethylamine, dimethylaminopyridine and mixture thereof. 30. The process as claimed in claim 26, wherein the reaction is carried out in a suitable solvent; wherein the solvent is selected from amides, sulfoxides, aromatic hydrocarbons, water and mixtures thereof. 31. The process as claimed in claim 30, wherein the solvent is selected from the group comprising dimethylacetamide, dimethylformamide, N- methylpyrrolidone, dimethyl sulfoxide, diethyl sulfoxide, toluene, xylene, diphenyl ether and mixture thereof. 32. The process as claimed in claim 30, wherein the solvent is xylene, water and mixtures thereof.

33. The process as claimed in claim 26, wherein the step b) is carried out at a temperature of about 100°C to about 150°C. 34. A process for preparation of caronic amide of Formula VI or a salt thereof, comprising reacting a caronic acid of Formula III or a salt thereof with a suitable source of amine and a solvent containing at least one of caronic acid, mono amide and diamide impurities 35. The process as claimed in claim 34, wherein the solvent is selected from the group comprising dimethylacetamide, dimethylformamide, N- methylpyrrolidone, dimethyl sulfoxide, diethyl sulfoxide, toluene, xylene, diphenyl ether and mixture thereof. 36. The process as claimed in claim 34, wherein the suitable source of amine is selected from the group comprising urea, ammonia, formamide and mixtures thereof. 37. A process for purification of caronic amide of Formula VI or a salt thereof, comprising: a) suspending or dissolving caronic amide of Formula VI or a salt thereof in a suitable solvent at a suitable temperature, and b) isolating the pure caronic amide of Formula VI or a salt thereof. 38. The process as claimed in claim 37, wherein the suitable solvent is selected from the group comprising ethyl acetate, methyl acetate, tetrahydrofuran, dimethyl ether, isopropyl ether, methyl tertiary butyl ether, 1,4-dioxane, acetone, methyl isobutyl ketone, methyl ethyl ketone, acetonitrile, propionitrile, methylene chloride, ethylene chloride, chloroform, hexane, heptane, pentane, cyclohexane, cycloheptane, cyclopentane, toluene, xylene, and water and mixture thereof.

39. The process as claimed in claim 38, wherein the suitable solvent is ethyl acetate, acetonitrile, water or mixtures thereof. 40. The process as claimed in claim 38, wherein the step a) is carried out at a temperature of about 50°C to about 60°C. 41. A process for preparation of compound of Formula III or a salt thereof, comprising: reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III. 42. The process as claimed in claim 41, wherein the R is selected from the group comprising methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert butyl, bromo, chloro or Iodo. 43. The process as claimed in claim 41, wherein the suitable oxidizing agent is selected from the group comprising bromine, hydrogen peroxide, Potassium persulfate, sodium persulfate, ammonium persulfate, potassium monopersulfate, sodium monopersulfate, potassium permanganate, sdoium permanganate and mixture thereof. 44. The process as claimed in claim 41, wherein the R is chloro and wherein the suitable oxidizing agent is potassium permanganate. 45. The process as claimed in claim 41, wherein the reaction is carried out at a temperature of about 35°C to about 40°C. 46. A process for preparation of nirmatrelvir or boceprevir, comprising: preparing the compound of Formula III, compound of Formula V and /or compound of Formula VI according to claims-1 to 45; and converting the compound of Formula III, compound of Formula V and /or compound of Formula VI into nirmatrelvir or boceprevir.

Description:
“PROCESS FOR PREPARATION OF AZABICYCLO [3.1.0] HEXANE INTERMEDIATES” PRIORITY: This application claims the benefit under Indian Provisional Application No.(S) 202241014235 filed on 16 th March, 2022 entitled “Process for preparation of azabicyclo [3.1.0] hexane intermediates” and 202241020524 filed on 05 th April, 2022 entitled “Process for preparation of azabicyclo [3.1.0] hexane intermediates” the contents of each of which are incorporated by reference herein. FIELD OF THE INVENTION The present invention relates to a process for preparation of azabicyclo [3.1.0] hexane intermediate of Formula-I, a useful intermediates in the preparation of certain antiviral compounds for example boceprevir and nirmatrelvir. Formula I wherein “R1” is selected from hydrogen, alkyl, aryl or aralkyl BACKGROUND OF THE INVENTION Azabicyclo [3.1.0] hexane intermediates are valuable intermediate in the preparation of certain antiviral compounds for example boceprevir an important drug for the treatment of human hepatitis C virus infections (HCV) and nirmatrelvir, recently approved drug for the treatment of COVID-19. Boceprevir and Nirmatrelvir, chemically known as (1R,5S)-N-[3-Amino-1- (cyclobutylmethyl)-2,3dioxopropyl]-3-[2(S)-[[[(1,1-dimethyle thyl)amino]carbonyl] amino]-3,3-dimethyl-1-oxobutyl]-6,6-dimethyl-3azabicyclo[3.1 .0]hexan-2(S)- carboxamide and (1R,2S,5S)-N-((1S)-1-Cyano-2-((3S)-2-oxopyrrolidin-3-yl)ethy l)-3- ((2S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl)-6,6 -dimethyl-3-azabicyclo [3.1.0] hexane-2-carboxamide and are having the following chemical structures:

Various known literatures for example: WO2004/113295, CN101020680A, CN101863866B, WO2007/075790, WO2010/08828, WO2012/049688 and WO2014/061034 disclosed preparation of azabicyclo [3.1.0] hexane intermediate of Formula I. The process disclosed in art is as follows: The processes disclosed in the art involves preparation of benzyl caronic amide of Formula V or Formula VI staring from alkyl ester of either chrysanthemic acid or cypermethric acid by oxidation in presence of potassium permanganate or ozone in acetone or a mixture of acetone: water and followed by ester hydrolysis to obtain caronic acid of Formula III. The obtained caronic acid of Formula III was cyclized to caronic anhydride in presence of acetic anhydride and then the caronic anhydride was converted to benzyl caronic amide of Formula V followed by de-benzylation to obtain the caronic amide of Formula VI followed by formation of azabicyclo [3.1.0] hexane intermediate of Formula I in multiple ways by involving different chemical conversions as described above. The processes described under the known literatures involves lengthy process to prepare compound of Formula III, Formula V and Formula VI, for example use of alkyl ester of either chrysanthemic acid or cypermethric acid in the preparation of Formula III and use of caronic anhydride in the preparation of protected caronic amide of Formula V and finally de-protection to obtain caronic amide of Formula VI, involves one or more additional steps of esterification and then hydrolysis and also formation of anhydride, which steps makes the process lengthy thereby the intermediates produced with these processes are relatively expensive. Hence, it’s important to develop a simple and cost effective process for preparation of compound of Formula III, Formula V and Formula VI for making azabicyclo [3.1.0] hexane intermediate of Formula I with high yield and cost effective. SUMMARY OF THE INVENTION Accordingly, the present invention provides an improved process for preparation of intermediates of azabicyclo [3.1.0] hexane of Formula I specifically compound of Formula III, Formula V and Formula VI. In accordance with one embodiment, the present invention provides a process for preparation of a compound of Formula III or a salt thereof, comprising: reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain compound of Formula III. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula III or a salt thereof, comprising: reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula III or a salt thereof with benzyl amine to obtain a compound of Formula IV or a salt thereof, and b) cyclizing the compound of Formula IV or a salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, wherein R is alkyl or halogen, b) reacting the compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and c) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, wherein R is alkyl or halogen, b) reacting the compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and c) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, wherein R is alkyl or halogen, b) reacting the compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and c) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V; wherein the steps a) to c) are carried out in one-pot reaction. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula III or a salt thereof, comprising: reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain compound of Formula III. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula III or a salt thereof, comprising: reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain compound of Formula III; wherein both the compound of Formula IIa or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, Formula III Formula IIa b) reacting the compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and Formula III Formula IV c) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, b) reacting the compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and c) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V; wherein the steps a) to c) are carried out in one-pot reaction. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: reacting a compound of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: reacting a compound of Formula III or a salt thereof with a suitable source of amine in presence of a suitable catalyst to obtain caronic amide of Formula VI. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: reacting a compound of Formula III or a salt thereof with a suitable source of amine in presence of a suitable catalyst and a suitable solvent to obtain caronic amide of Formula VI. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: reacting a compound of Formula III or a salt thereof with a suitable source of amine in presence of a suitable solvent to obtain caronic amide of Formula VI. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III or a salt thereof, and b) reacting the compound of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III or a salt thereof, and b) reacting the compound of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III or a salt thereof, and b) reacting the compound of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III or a salt thereof, and b) reacting the compound of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI; wherein both the compound of Formula IIa or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. In accordance with another embodiment, the present invention provides a process for purification of caronic amide of Formula VI or a salt thereof, comprising: a) suspending or dissolving caronic amide of Formula VI or a salt thereof in a suitable solvent at a suitable temperature, and b) isolating the pure caronic amide of Formula VI or a salt thereof. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula III or a salt thereof with a suitable source of amine optionally in presence of a suitable solvent and/or a suitable catalyst to obtain a caronic amide of Formula VI, b) suspending or dissolving the caronic amide of Formula VI or a salt thereof obtained in step a) in a suitable solvent at a suitable temperature, and c) isolating caronic amide of Formula VI or a salt thereof. In accordance with another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula IIa or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III or a salt thereof, b) reacting the compound of Formula III or a salt thereof with a suitable source of amine optionally in presence of a suitable solvent and/or a suitable catalyst to obtain a caronic amide of Formula VI, c) suspending or dissolving the caronic amide of Formula VI or a salt thereof obtained in step b) in a suitable solvent at a suitable temperature, and d) isolating caronic amide of Formula VI or a salt thereof. In accordance with another embodiment, the present invention provides an improved process for preparation of compound of Formula I, comprising: a) preparing a compound of Formula III or Formula V or Formula VI according to the processes described as above embodiments, and b) converting the compound of Formula III or Formula V or Formula VI in to compound of Formula I; wherein the “R1” is selected from hydrogen, alkyl, aryl or aralkyl. In accordance with another embodiment, the present invention provides an improved process for preparation of boceprevir, comprising: a) preparing a compound of Formula III or Formula V or Formula VI according to the processes described as above embodiments, b) converting the compound of Formula III or Formula V or Formula VI into compound of Formula I, and c) converting the compound of Formula I in to boceprevir. In accordance with another embodiment, the present invention provides an improved process for preparation of nirmatrelvir, comprising: a) preparing a compound of Formula III or Formula V or Formula VI according to the processes described as above embodiments, b) converting the compound of Formula III or Formula V or Formula VI into compound of Formula I, and c) converting the compound of Formula I in to nirmatrelvir. In accordance with another embodiment, the present invention provides a composition comprising boceprevir or nirmatrelvir, prepared by the process of compound of Formula III, Formula V, Formula VI and/or Formula I of the present invention and at least one pharmaceutically acceptable excipient. DETAILED DESCRIPTION OF THE INVENTION The present invention provides an improved process for preparation of intermediates of azabicyclo [3.1.0] hexane of Formula I specifically compound of Formula III, Formula V and Formula VI. The present invention encompasses an improved process for the preparation of intermediates of azabicyclo [3.1.0] hexane of Formula I with high product yield and quality wherein “R1” is selected from hydrogen, alkyl, aryl or aralkyl Wherein the improvements include oxidation at acid compound of Formula II or its salt thereof; wherein “R” is alkyl or halogen, in which alkyl esterification and subsequent ester hydrolysis steps as disclosed in the art are not necessary. Further during the process for preparation of benzyl caronic amide of Formula V the formation of intermediate caronic anhydride as disclosed in the art is not necessary instead the compound of Formula III is directly converted to benzyl caronic amide of Formula V with the help of Benzyl amine. Further, the present invention also involve preparation of caronic amide of Formula VI by direct cyclization of caronic acid of Formula III without involving formation of caronic anhydride, protected caronic amide and subsequent deprotection steps. In accordance with one embodiment, the present invention provides a process for preparation of compound of Formula III or a salt thereof, comprising: reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain compound of Formula III. In another embodiment, the present invention provides a process for preparation of compound of Formula III or a salt thereof, comprising: reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity. Unless otherwise specified the term “alkyl” used herein is selected from but not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert butyl and the like. Optionally the alkyl may be further substituted with a suitable substituent, which may be selected from the group comprising halogen, aryl and the like. Unless otherwise specified the term “halogen” used herein is selected from bromo, chloro or Iodo. In another preferred embodiment, the compound of Formula II specifically represents as following compound of Formula IIa: The compound of Formula II, preferably Formula IIa which is used herein as a starting material is known in the art and can be prepared by any known methods. For example, may be prepared as per the process disclosed in US4237058. The suitable oxidizing agent used in aforementioned process is selected from the group consisting of but not limited to bromine, hydrogen peroxide (H 2 O 2 ), Potassium persulfate (K 2 S 2 O 8 ), sodium persulfate (Na 2 S 2 O 8 ), ammonium persulfate ((NH 4 ) 2 S 2 O 8 ), potassium monopersulfate (KHSO 5 ), sodium monopersulfate (NaHSO5), potassium permanganate (KMnO 4 ), sodium permanganate (NaMnO 4 ) and the like and mixture thereof; preferably bromine, sodium persulfate, potassium permanganate and mixture thereof; more preferably potassium permanganate. The aforementioned oxidation step may be carried out in presence of a suitable solvent and / or a base. The suitable solvent selected from the group consisting of ethers, esters, ketones, halogenated hydrocarbons, aprotic organic solvents, water and mixture thereof. Ethers include but are not limited to tetrahydrofuran, dimethyl ether, isopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; esters include but are not limited to ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and the like; ketones include but are not limited to acetone, methyl ethyl ketone, methyl isobutyl ketone and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, ethylene chloride, chloroform and the like; aprotic organic solvent, include but are not limited to N,N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide, 1,3-dimethyl-2- imidazolidinone, acetonitrile and the like; water and mixture thereof; preferably acetone, methylene chloride, water and mixture thereof; more preferably water. The suitable base may be selected from the group consisting of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium-butoxide, potassium hydroxide, potassium carbonate, potassium bicarbonate, triethyl amine, diisopropyl ethyl amine and the like and mixtures thereof; preferably sodium hydroxide or potassium hydroxide and more preferably sodium hydroxide. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity; preferably added in about 4 to about 5 parts of the total quantity. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 equal parts of the total quantity; preferably added in about 4 to about 5 equal parts of the total quantity. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity in a sequential manner one after another; preferably added in about 4 to about 5 parts of the total quantity in a sequential manner one after another. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 equal parts of the total quantity in a sequential manner one after another; preferably added in about 4 to about 5 equal parts of the total quantity in a sequential manner one after another. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein both the compound of Formula II or a salt thereof and the oxidizing agent are added in about 3 to about 10 parts of the total quantity in a sequential manner one after another at a temperature of about 0°C to about 60°C; preferably added in about 4 to about 5 parts of the total quantity in a sequential manner one after another at a temperature of about 20°C to about 30°C. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein the compound of Formula II or a salt thereof is added in about 3 to about 10 parts of the total quantity in about 30 min to about 4 hrs; preferably added in about 4 parts of the total quantity in about 1 hr to about 2 hrs. In a preferred embodiment, the present invention provides a process for preparation of compound of Formula III; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity in about 5 min to 30 mins; preferably added in about 5 parts of the total quantity in about 10 min to about 15 mins. In another embodiment, the present invention provides a process for preparation of compound of Formula III; wherein the total quantity of oxidizing agent is about 1.5 to about 5 equivalents to starting compound of formula IIa. In another embodiment, the present invention provides a process for preparation of compound of Formula III; wherein the oxidizing agent is added in about 3 to about 10 parts of the total quantity and each part contains about 0.15 to 1.65 equivalents to starting compound of formula IIa; preferably added in about 5 parts of the total quantity and each part contains about 0.2 to 1.5 equivalents to starting compound of formula IIa. Optionally, the aforementioned oxidation step may be carried out in presence of a suitable acid, wherein the acid is selected from the group consisting of acetic acid, propanoic acid, p-toluenesulfonic acid and benzoic acid and the like and mixture thereof. The reaction of a Formula IIa or a salt thereof with a suitable oxidizing agent is carried out at a temperature of about 25°C to reflux temperature; preferably at about 25°C to about 65°C; more preferably at about 35°C to about 40°C. After completion of the reaction, the resultant compound of Formula III may be advantageously processed to next step or optionally the obtained compound of Formula III can be isolated from the reaction mass by conventional techniques such as precipitation by cooling the reaction mass, isolated by solvent extraction or precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration; preferably if isolation involves compound of Formula III can be isolated by adjusting the pH of the reaction to about less than 2.0 with a suitable acid such as hydrochloric acid, sulfuric acid and the like; preferably with sulfuric acid at a temperature of about 5°C to about 15°C and extracting the compound of Formula III with a suitable water immiscible organic solvent such as ethyl acetate, methylene chloride and the like; preferably with ethyl acetate and concentrating the product containing organic layer . The present invention provides a compound of Formula III prepared by the process described as above having a purity of at least about 95%, as measured by HPLC, preferably at least about 97% as measured by HPLC. In another embodiment, the present invention provides an improved process for the preparation of benzyl caronic amide of Formula V, comprising preparing the caronic acid of Formula III as process just described as above, and converting the caronic acid of Formula III in to benzyl caronic amide of Formula V. In another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and b) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain a compound of Formula V. The compound of Formula III, which is used herein as a starting material, can be prepared by the process as in accordance with above embodiments or any methods known in art. The step a) reaction may be carried out with a suitable solvent, wherein the suitable solvent is selected from the group consisting of but not limited to amides, sulfoxides, aromatic hydrocarbons and the like and mixtures thereof. The amides include, but are not limited to dimethylacetamide, dimethylformamide, N- methylpyrrolidone and the like and mixtures thereof; sulfoxides include, but are not limited to dimethyl sulfoxide, diethyl sulfoxide and the like and mixtures thereof; aromatic hydrocarbons include, but are not limited to toluene, xylene and the like and mixture thereof; preferably dimethyl sulfoxide, toluene, xylene and the like and mixture thereof; more preferably xylene. In another embodiment, optionally the step a) reaction may be carried without use of any solvent as mentioned above as the reactant benzyl amine is used as both reactant and solvent. In another embodiment, the benzyl amine used in the current invention can be substituted or unsubstituted benzyl amine, wherein the substituents include but are not limited to halo such as bromo, chloro or fluoro, iodo; C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert butyl and the like; O-alkyl such as methoxy, ethoxy and the like; aryl such as phenyl and the like; or O-aryl such as benzyloxy and the like. Optionally the C1- 4 alkyl, aryl and O-aryl may be further substituted with a suitable substituent, which may be selected from the group comprising halogen, aryl and the like. The reaction of Formula III or salt thereof with benzyl amine is carried out at a temperature of about 50°C to reflux temperature; preferably at about 100°C to about 150°C; more preferably at about 135°C to about 145°C. After completion of the step a) reaction, the resultant compound of Formula IV may be isolated as a solid or as such reaction mass may be converted to a compound of Formula V without isolating the compound of Formula IV as solid by directly adding a suitable cyclizing agent to the step a) solution. The suitable cyclizing agent used in the step b) is selected from the group consisting of but not limited to acetic anhydride, sulfuric acid, para toluene sulfonic acid and the like and mixture thereof; preferably acetic anhydride. The cyclization reaction of step b) is carried out at a temperature of about 50°C to reflux temperature; preferably at about 100°C to about 150°C; more preferably at about 135°C to about 145°C. After completion of the step b) reaction, the resultant compound of Formula V can be isolated by conventional techniques such as precipitation by cooling the reaction mass, isolated by solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration; preferably isolated by concentrating the reaction mass under vacuum at below 80°C and followed by adding a suitable solvent such as isopropanol and then filtering the product. In accordance with another embodiment, the present invention provides a process for preparation of compound of Formula V, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III, wherein R is alkyl or halogen, b) reacting the compound of Formula III or salt thereof with benzyl amine to obtain a compound of Formula IV or salt thereof, and c) cyclizing the compound of Formula IV or salt thereof in presence of a suitable cyclizing agent to obtain compound of Formula V; wherein the steps a) to c) are carried out in one-pot reaction. The aforementioned step a) to step c) are carried out in one-pot reaction by following the process as described in above embodiments of the present invention. In another embodiment, compound of Formula V obtained by the processes described as above, having purity of at least about 99% as measured by HPLC, preferably at least about 99.5% as measured by HPLC. Compound of Formula III and Formula V are key cost contributor in the preparation of certain antiviral compounds for example boceprevir and nirmatrelvir. Preparation of caronic acid of Formula III according to the prior art involves oxidation of either chrysanthemic acid ester or cypermethric acid ester in presence of potassium permanganate or ozone in acetone or a mixture of acetone and water and followed by ester hydrolysis. The oxidation process disclosed under the prior literatures suffers from forming a heterogeneous reaction mass throughout the reaction and this may be due to the use of alkyl ester intermediates in acetone or a mixture of acetone and water. Due to the heterogeneous reaction system the oxidizing agent used in the process may not be available for complete oxidation as a result additional quantities of oxidizing agent required to complete the reaction, therefore inconsistent output with low pure and lower yields. Further the oxidation at ester compound of Formula II as disclosed under the prior literature involves addition of oxidizing agent to the total quantity of starting material of Formula II in either acetone or a mixture of acetone and water. Generally oxidizing agent like potassium permanganate is having tendency with rapid reactivity with the starting material which leads to instant release of excess oxygen and high chances of sudden shoot up of reaction pressure and temperature thereby high chances of explosion. Further, the disclosed processes involves preparation of benzyl caronic amide of Formula V in two steps, which involves first cyclization of caronic acid of Formula III to form caronic anhydride followed by amide formation. The two step process disclosed under the prior literatures not only lengthy but also requires additional step of isolation and drying process of caronic anhydride, which leads to operational inconvenience and burden on equipment occupancy. In order to overcome the difficulties associated with the prior processes, the present inventors have found that below modifications can be improved the process of getting Formula III and/or Formula V with high yields and high purity: 1) oxidation reaction may be carried out at corresponding acid compound of Formula II as a salt instead of alkyl ester as disclosed in the prior art, which process makes the reaction homogeneous thereby complete conversion of starting material without need of any excess quantity of oxidizing agent. 2) The use of acid compound of Formula II is not only advantage in making homogeneous but also avoids the necessity of ester formation and subsequent hydrolysis step, as these steps are necessary when the process utilizes alkyl ester of Formula II as a starting material, 3) Oxidation reaction may be carried out with part-wise addition of both the starting material and oxidizing agent sequentially one after another. This modification substantially reduces the chances of pressure shoot up and temperature build up in the reaction thereby there is no any safety concern, and 4) For making compound of formula V, prior literature proposes two-step process, where in which isolation of caronic anhydride as intermediate is mandatory whereas the present invention bypass the formation of caronic anhydride as intermediate therefore the present invention is advantage in commercial scale. In another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof. In another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: a) reacting a compound of Formula II or a salt thereof with a suitable oxidizing agent to obtain a compound of Formula III or a salt thereof, and b) reacting the compound of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI. In another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising: reacting a caronic acid of Formula III or a salt thereof with a suitable source of amine to obtain caronic amide of Formula VI. The compound of Formula III, which is used herein as a starting material is known in the art and can be prepared by any known methods. For example, can be prepared as per the process disclosed in the above embodiments or can be prepared by following the process disclosed in WO2004/113295. Reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine may be carried out either in neat reaction or in a suitable solvent, wherein the suitable solvent is selected from the group consisting of but not limited to amides, sulfoxides, aromatic hydrocarbons and the like, water and mixtures thereof. The amides include, but are not limited to dimethylacetamide, dimethylformamide, N- methylpyrrolidone and the like; sulfoxides include, but are not limited to dimethyl sulfoxide, diethyl sulfoxide and the like; aromatic hydrocarbons include, but are not limited to toluene, xylene, diphenyl ether and the like and mixture thereof; preferably dimethyl sulfoxide, toluene, xylene, water and mixtures thereof; more preferably xylene, water and mixtures thereof. The source of amine is selected from the group consisting of but not limited to urea, ammonia, formamide and the like and mixtures thereof. Optionally reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine may be carried out in presence of a suitable catalyst, wherein the suitable catalyst is selected from the group consisting of but not limited to 1,8-Diazabicyclo[5.4.0]undec- 7-ene (DBU), triethylamine, trimethylamine, dimethylamine, diethylamine, dibenzoyl peroxide, toluene-4-sulfonic acid, hydrogen peroxide, pyridine, dimethylaminopyridine, acetic acid, tetrabutyl ammonium bromide, azobisisobutyronitrile, copper(I)/DBU catalyst, copper(II) acetate, copper(I) bromide, iron(III) acetylacetonate, ruthenium based catalysts, molecular sieves, tetra methyl guanidine, 7-methyl-1,5,7- triazabicyclo[4.4.0]dec-5-ene, triazabicyclo[4.4.0]dec-5-ene, 1,5-diazabicyclo[4.3.0] non-5-ene, proton sponge, 1,4-diazabicyclo[2.2.2]octane/tri ethylene diamine and the like and mixture thereof; preferably 1,8-Diazabicyclo[5.4.0]undec-7-ene, triethylamine, dimethylamine, pyridine, dimethylaminopyridine and mixture thereof; more preferably 8-Diazabicyclo[5.4.0]undec-7-ene, triethylamine, dimethylaminopyridine and mixture thereof. In another embodiment, the reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine is carried out in presence of a suitable catalyst. In another embodiment, the reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine is carried out in presence of a suitable catalyst and a suitable solvent. In another embodiment, the reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine is carried out in presence of a suitable solvent. The reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine is carried out at a temperature of about 50°C to about 200°C; preferably at about 100°C to about 150°C; more preferably at about 135°C to about 145°C. Then the compound of Formula VI may be isolated from the reaction mass by conventional techniques such as solvent extraction, solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration; preferably isolated by cooling the reaction mass and filtering the solids. In another embodiment, preparation of caronic amide of Formula VI or a salt thereof by reaction of caronic acid of Formula III or a salt thereof with a suitable source of amine is always possibility to formation of mono amide and/or diamide impurities along with unreacted starting material and these impurities mostly separated through the mother liquors. The mono amide and diamide impurities specifically represents as following compounds: The present inventors have surprisingly found that the mother liquors which contain unwanted impurities such as unreacted caronic acid and/or mono amide and/or diamide impurities are utilized as solvent source for the additional batches of the process of the above embodiments. The reuse of mother liquors as solvent source is advantageously increases the overall product yield as the unwanted impurities accumulated in the mother liquors are converted into compound of Formula VI in each batch of the process. In another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising reacting a caronic acid of Formula III or a salt thereof with a suitable source of amine and mother liquors containing unwanted impurities selected from unreacted caronic acid and/or mono amide and/or diamide impurities obtained from the above embodiments. In another embodiment, the present invention provides a process for preparation of caronic amide of Formula VI or a salt thereof, comprising reacting a caronic acid of Formula III or a salt thereof with a suitable source of amine and mother liquors containing unwanted impurities selected from unreacted caronic acid and/or mono amide and/or diamide impurities obtained from the above embodiments; wherein the source of amine, reaction temperature and other process conditions are same as the process as described just as above. The present invention provides a compound of Formula VI or a salt thereof prepared by the process described as above having a purity of at least about 97%, as measured by HPLC, preferably at least about 99% as measured by HPLC; and having less than 0.5%, preferably less than 0.2% each of unreacted starting material caronic acid and/or mono amide and/or diamide impurities as measured by HPLC. In another embodiment, the caronic amide of Formula VI or a salt thereof prepared by the process of the present invention or prepared by any other processes is further purified to remove impurities such as mono amide and/or diamide impurities along with unreacted starting material by solvent purification. In another embodiment, the present invention provides a process for purification of caronic amide of Formula VI or a salt thereof, comprising: a) suspending or dissolving caronic amide of Formula VI or a salt thereof in a suitable solvent at a suitable temperature, and b) isolating the pure caronic amide of Formula VI or a salt thereof. The step a) process may be involve suspending or dissolving a compound of Formula VI having unreacted caronic acid and/or mono amide and/or diamide impurities more than 0.5% by HPLC in a suitable solvent at a temperature of about ambient temperature to reflux temperature; preferably at about 50°C to about 60°C. The suitable solvent used to suspend or dissolve compound of Formula VI having about more than 0.5% unreacted caronic acid and/or mono amide and/or diamide impurities by HPLC is selected from the group consisting of but is not limited to esters, ethers, ketones, nitriles, halogenated hydrocarbons, aliphatic or alicyclic hydrocarbons, aromatic hydrocarbons and the like, water and mixtures thereof. The esters include, but are not limited to ethyl acetate, methyl acetate and the like; ethers include, but are not limited to tetrahydrofuran, dimethyl ether, isopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; ketones include, but are not limited to acetone, methyl isobutyl ketone, methyl ethyl ketone and the like; nitriles include, but are not limited to acetonitrile, propionitrile and the like; halogenated hydrocarbons include, but are not limited to methylene chloride, ethylene chloride, chloroform and the like; aliphatic or alicyclic hydrocarbons include, but are not limited to hexane, heptane, pentane, cyclohexane, cycloheptane, cyclopentane and the like; aromatic hydrocarbons include, but are not limited to toluene, xylene and the like and mixture thereof; preferably ethyl acetate, acetonitrile, water and mixture thereof; more preferably water. Then the pure compound of Formula VI having unreacted caronic acid and/or mono amide and/or diamide impurities less than 0.5% by HPLC may be isolated from the reaction mass by conventional techniques such as solvent extraction, solvent precipitation, crystallization, concentrated by subjecting the solution to heating, decantation or filtration; preferably isolated by cooling the reaction mass and filtering the solids. In another embodiment, the compound of Formula VI obtained by the processes described as above, having purity of at least about 99% as measured by HPLC, preferably at least about 99.5% as measured by HPLC and less than 0.5%, preferably less than 0.2% as measured by HPLC of each of unreacted starting material caronic acid and/or mono amide and/or diamide impurities. Compound of Formula VI is the key cost contributor in the preparation of certain antiviral compounds for example boceprevir and nirmatrelvir. The disclosed processes involve preparation of caronic amide of Formula VI in three steps, which involves first cyclization of caronic acid of Formula III to form caronic anhydride, amide formation to obtain protected caronic amide and followed by de-protection. These three step process disclosed under the prior literatures not only lengthy but also requires additional step of isolation and drying process of caronic anhydride and protected caronic amide, which leads to operational inconvenience and burden on equipment occupancy. The present invention encompasses an improved process for the preparation of compound of Formula VI with high yields and high purity by direct reaction of caronic acid of Formula III with a source of amine, without involving formation of caronic anhydride, protected caronic amide and subsequent deprotection steps using hazardous deprotecting agents. The term "catalyst" as used in this application means a substance that increases reaction rate by altering the reaction mechanism. The term "Neat reaction" as used in this application means a step forward in the direction of solvent free reactions and an alternative approach that eliminates the use of a solid support as well as solvent from the reaction. The term "one-pot" as used in this application means a process uses a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one solvent/reactor. This is much desired by chemists because avoiding a lengthy separation process and purification of the intermediate chemical compounds can save time and resources, improves the efficiency of a chemical reaction, and offers better chemical yield. The present invention encompasses an improved process for the preparation of intermediates of azabicyclo [3.1.0] hexane of Formula I with high product yield and quality by the following scheme: In accordance with another embodiment, the present invention provides an improved process for the preparation of compound of Formula I, comprising preparing the compound of Formula V and/or compound of Formula VI as process described above, and converting the compound of Formula V and/or compound of Formula VI in to compound of Formula I by any process known in the art for example WO2004/113295, CN101020680A, CN101863866B, WO2007/075790, WO2010/08828, WO2012/049688 and WO2014/061034. In accordance with another embodiment, the present invention provides use of compound of Formula V and/or compound of Formula VI prepared as process described above, as an intermediate in the preparation of certain antiviral compounds for example boceprevir or nirmatrelvir. EXAMPLES The following non-limiting examples illustrate specific embodiments of the present invention. They are not intended to be limiting the scope of the present invention in any way. EXAMPLE-1: Preparation of compound of Formula III (addition of both Formula IIa and oxidizing agent - in part wise one after another sequentially) Compound of Formula IIa (100 g), water (500 mL) were added in to a round bottom flask at 20-30°C. To the reaction mass was added aqueous sodium hydroxide (26 mL) at 20- 30°C and stir for 10 min at same temperature. Then the solution was divided in to 4 equivalent parts and kept a side (4×150 mL). In another round bottom flask was added water (500 mL) and first part of potassium permanganate (37.8 g) at 20-30°C and stir for 10 min. To the reaction mass was added first part of solution of Formula IIa (150 mL) for a period of 1.5 to 2 hrs at 20-30°C. To the reaction mass was added second part of potassium permanganate (37.8 g) at 20-30°C and followed by addition of second part of solution of Formula IIa (150 mL) for a period of 1.5 to 2 hrs at same temperature and repeat the addition of potassium permanganate and Formula IIa in another three lots at same temperature. Reaction mass was heated to 35-40°C and stir for 2-4 hrs at same temperature. After completion of the reaction by TLC, cool the reaction mass to 10°C and was added sodium metabisulfite solution at below 30°C and stir for 60 min at same temperature. Reaction mass pH was adjusted to less than 2.0 with sulphuric acid (187 g) and stir for 60 min. To the reaction mass was added ethyl acetate (600 mL), filtered and washed the wet cake with water (100 mL). Then the product containing organic layer was separated and concentrated under vacuum at below 55°C. To the obtained solid was added water (100 mL) and cool to 5°C and stir for 2-3 hrs at same temperature. Filtered the solids and washed the wet cake with chilled water and dry the wet material at 60-70°C to obtain title compound. Wt.: 70 g. Purity by HPLC: 99%. Note: Each lot of potassium permanganate addition is slightly exothermic; the Maximum Temperature of the Synthesis Reaction (MTSR) during KMnO 4 lots addition in worst case is 28ºC. Oxygen gas liberation observed during KMnO 4 lots addition at 25ºC and digestion at 38ºC with peak gas flow rate of 4.75L/min/kg was observed. EXAMPLE-2: Preparation of compound of Formula V Compound of Formula III (100 g), o-xylene (400 mL) were added in to a round bottom flask with dean stark condenser at 20-30°C. Reaction mass heated to 135-140°C and was added benzyl amine solution (68 g was dissolved in 100 mL o-xylene) in 3-4 hrs at same temperature. Reaction mass was stir for 2-3 hrs at 140-145°C (water was collected by azeotropically). Reaction mass was allowed to cool to 30-35°C and was added acetic anhydride (13 g) at same temperature. Reaction mass was heated to 140-145°C and stir for 2-3 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80°C and concentrated under vacuum and co-distilled with isopropyl alcohol (100 mL) at below 80°C. To the obtained residue was added isopropyl alcohol (150 mL) at 25-30°C and stir for 2-3 hrs at same temperature. Reaction mass was cool to 0-5°C, filtered the solids and washed the wet cake with chilled isopropyl alcohol (100 mL) and dry the wet material at 60-65°C to obtain title compound. Wt.: 120 g. Purity by HPLC: 99.5%. EXAMPLE-3: One pot process of compound of Formula V Compound of Formula IIa (100 g), water (500 mL) were added in to a round bottom flask at 20-30°C. To the reaction mass was added aqueous sodium hydroxide (26 mL) at 20- 30°C and stir for 10 min at same temperature. Then the solution was divided in to 4 equivalent parts and kept a side (4×150 mL). In another round bottom flask was added water (500 mL) and first part of potassium permanganate (37.8 g) at 20-30°C and stir for 10 min. To the reaction mass was added first part of solution of Formula IIa (150 mL) for a period of 1.5 to 2 hrs at 20-30°C. To the reaction mass was added second part of potassium permanganate (37.8 g) at 20-30°C and followed by addition of second part of solution of Formula IIa (150 mL) for a period of 1.5 to 2 hrs at same temperature and repeat the addition of potassium permanganate and Formula IIa in another three lots at same temperature. To the reaction mass was added third part of potassium permanganate (37.8 g) at 20-30°C and followed by addition of third part of solution of Formula IIa (150 mL) for a period of 1.5 to 2 hrs at same temperature. To the reaction mass was added fourth part of potassium permanganate (37.8 g) at 20-30°C and followed by addition of fourth part of solution of Formula IIa (150 mL) for a period of 1.5 to 2 hrs at same temperature. To the reaction mass was added fifth part of potassium permanganate (37.8 g) at 20-30°C and stir for 1-2 hrs at same temperature. Reaction mass was heated to 35- 40°C and stir for 2-4 hrs at same temperature. After completion of the reaction by TLC, cool the reaction mass to 10°C and was added sodium metabisulfite solution at below 30°C and stir for 60 min at same temperature. Reaction mass pH was adjusted to below 2.0 with sulphuric acid (187 g) at below 30°C and stir for 60 min at same temperature. To the reaction mass was added ethyl acetate (600 mL), filtered and washed the wet cake with water (100 mL). Then the product containing organic layer was separated and concentrated under vacuum at below 55°C. To the reaction mass was added o-xylene (400 mL) and transferred into a round bottom flask with dean stark condenser at 20-30°C. Reaction mass was heated to 135-140°C and was added benzyl amine solution (68 g in 100 mL o-xylene) in 3-4 hrs at same temperature. Reaction mass was stirred for 2-3 hrs at 140-145°C (19-20 mL of water was collected by azeotropically). Reaction mass was allowed to cool to 30-35°C and was added acetic anhydride (13 g) at same temperature. Reaction mass was heated to 140-145°C and stir for 2-3 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80°C and concentrated under vacuum and co-distilled with isopropyl alcohol (100 mL) at below 80°C. To the obtained residue was added isopropyl alcohol (150 mL) at 25-30°C and stir for 2-3 hrs at same temperature. Reaction mass was cool to 0-5°C, filtered the solids and washed the wet cake with chilled isopropyl alcohol (100 mL) and dry the wet material at 60-65°C to obtain title compound. Wt.: 124 g. Purity by HPLC: 99.2%. EXAMPLE-4: Preparation of compound of Formula III (from ethyl ester of compound of Formula II) Water (250 mL) was added in to a round bottom flask and heated to at 50-55°C. To the reaction mass was added potassium permanganate (20×3.14 g) and compound of Formula II ethyl ester (20×1.41 g) in part wise one after another sequentially at 50-55°C (observed heterogeneous reaction mass). After 2 hr of stirring, reaction was not completed by TLC. To the reaction mass was added additional potassium permanganate (2×9.4 g) and stirred for 1 hr. The heterogeneous reaction mass was allowed to cool to 10°C and was added sodium metabisulfite solution at below 30°C and stir for 60 min at same temperature. To the reaction mass was added sulphuric acid (94.5 g) at below 30°C and stir for 60 min at same temperature. To the heterogeneous reaction mass was added toluene (55 mL) and stir for 10 min at 30°C. Then the product containing organic layer was separated and concentrated under vacuum at below 65°C. The obtained residue was cool to 10°C and was added sodium hydroxide solution (22.5 g dissolved in 75 mL water) at same temperature. Reaction mass was heated to 50°C and stir for 2 hr at same temperature. After completion of the reaction, reaction mass was cool to 10°C and pH was adjusted to 1.0-2.0 with HCl (43 mL) and stir for 10 min at same temperature. Then the product was extracted with ethyl acetate (2×85 mL) and concentrated to obtain the title compound. Wt.: 8.1 g. Purity by HPLC: 92.1%. EXAMPLE-5: Preparation of compound of Formula III (from ethyl ester of compound of Formula II) Water (300 mL) and acetone (75 mL) was added in to a round bottom flask and heated to at 25-30°C. To the reaction mass was added potassium permanganate (128.5 g) at 25- 30°C and stir for 10 min at same temperature. To the reaction mass was added slowly compound of Formula II ethyl ester (56.5 g) in 7-8 hr at 25-30°C (observed heterogeneous reaction mass). Reaction mass was heated to 35-40°C. After 4 hr of stirring, reaction was not completed by TLC. To the reaction mass was added potassium permanganate (2×7.6 g) and stir for 1 hr. The heterogeneous reaction mass was allowed to cool to 10°C and was added sodium metabisulfite solution at below 30°C and stir for 60 min at same temperature. To the reaction mass was added sulphuric acid (189 g) at below 30°C and stir for 60 min at same temperature. To the heterogeneous reaction mass was added toluene (220 mL) and stir for 10 min at 30°C. Then the product containing organic layer was separated and concentrated under vacuum at below 65°C. The obtained residue was cool to 10°C and was added sodium hydroxide solution (45 g dissolved in 150 mL water) at same temperature. Reaction mass was heated to 50°C and stir for 2 hr at same temperature. After completion of the reaction, reaction mass was cool to 10°C and pH was adjusted to 1.0-2.0 with HCl (85 mL) and stir for 10 min at same temperature. Then the product was extracted with ethyl acetate (2×300 mL) and concentrated to obtain the title compound. Wt.: 20.5 g. Purity by HPLC: 93.5%. EXAMPLE-6: Preparation of compound of Formula VI Compound of Formula III (100 g), Urea (43.7 g) and water (200 mL) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and stir for 2-3 hrs at same temperature. Reaction mass was cool to 70-75°C and was added 1,8- diazabicyclo[5.4.0]undec-7-ene (10 g) at same temperature. Reaction mass was heated to 135-145°C and stir for 3-4 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (200 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 86 g. Purity by HPLC: 99.8%; Formula III by HPLC: Not detected; mono amide by HPLC: 0.1% and di amide by HPLC: 0.05%. EXAMPLE-7: Preparation of compound of Formula VI Compound of Formula III (100 g), Urea (43.7 g) and water (200 mL) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and stir for 24 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80- 85°C and was added water (200 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 79 g. Purity by HPLC: 99.7%; Formula III by HPLC: Not detected; mono amide by HPLC: 0.13% and di amide by HPLC: 0.06%. Taken mother liquors and tested for content of purity and impurity and the results are as follows: Formula VI by HPLC: 59.31%, Formula III by HPLC: 8.7%; mono amide by HPLC: 27.9% and di amide by HPLC: 3.7%. EXAMPLE-7a: Compound of Formula III (100 g), Urea (43.7 g) and mother liquors (200 mL) obtained from Ex-2 were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and stir for 24 hrs at same temperature. After completion of the reaction, reaction mass was allowed to cool to 80-85°C and was added water (200 mL) and stir for 30 min at same temperature. Then, reaction mass was further allowed to cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 84 g. Purity by HPLC: 99.62%; Formula III by HPLC: 0.08%; mono amide by HPLC: 0.25% and di amide by HPLC: 0.05%. Taken mother liquors and tested for content of purity and impurity and the results are as follows: Formula VI by HPLC: 77.03%, Formula III by HPLC: 9.76%; mono amide by HPLC: 9.7% and di amide by HPLC: 2.98%. EXAMPLE-7b: Compound of Formula III (100 g), Urea (43.7 g) and mother liquors (200 mL) obtained from Ex-2a were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and stir for 24 hrs at same temperature. After completion of the reaction, reaction mass was allowed to cool to 80-85°C and was added water (200 mL) and stir for 30 min at same temperature. Then, reaction mass was further allowed to cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 87 g. Purity by HPLC: 99.5%; Formula III by HPLC: 0.26%; mono amide by HPLC: 0.55% and di amide by HPLC: 0.12%. Taken mother liquors and tested for content of purity and impurity and the results are as follows: Formula VI by HPLC: 67.23%, Formula III by HPLC: 9.46%; mono amide by HPLC: 18.9% and di amide by HPLC: 3.83%. EXAMPLE-8: Preparation of compound of Formula VI Compound of Formula III (10 g) and Urea (4.3 g) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and collected the water during the heating and stir for 12 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (15 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 2 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (5 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 83 g. Purity by HPLC: 99.9%; Formula III by HPLC: 0.1%; mono amide by HPLC: 0.02% and di amide by HPLC: 0.03%. EXAMPLE-9: Preparation of compound of Formula VI Compound of Formula III (50 g) and ammonia solution (150 mL) were added in to a round bottom flask at 25-35°C. Reaction mass was heated to 160-165°C and collected the water during the heating and stir for 8-9 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added a mixture of cyclohexane and water (100 mL) and stir for 15 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled a mixture of cyclohexane and water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 83 g. Purity by HPLC: 99.4%; Formula III by HPLC: 0.5%; mono amide by HPLC: 0.1% and di amide by HPLC: 0.02%. EXAMPLE-10: Preparation of compound of Formula VI Compound of Formula III (10 g), Formamide (3.7 mL) and 4-Dimethylaminopyridine (0.7 g) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and collected the water during the heating and stirred for 20 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (15 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 2 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (5 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 7.9 g. Purity by HPLC: 99.6%; Formula III by HPLC: 0.06%; mono amide by HPLC: 0.13% and di amide by HPLC: 0.01%. EXAMPLE-11: Preparation of compound of Formula VI Compound of Formula III (50 g), Urea (21.8 g) and O-xylene (50 mL) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 130-140°C and collected the water during the heating and stirred for 24 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (150 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 2 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (25 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 39.5 g. Purity by HPLC: 99.8%; Formula III by HPLC: Not detected; mono amide by HPLC: 0.04% and di amide by HPLC: 0.2%. EXAMPLE-12: Preparation of compound of Formula VI Compound of Formula II (10 g), Urea (4.36 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.1 eq) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 130-140°C and stir for 4-8 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (20 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (5 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 7.4 g. EXAMPLE-13: Preparation of compound of Formula VI Compound of Formula III (10 g), Urea (4.36 g) and triethylamine (0.1 eq) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 130-140°C and stir for 4-8 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (20 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (5 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 7.1 g. EXAMPLE-14: Preparation of compound of Formula VI Compound of Formula III (100 g), Urea (43.7 g) and triethylamine (70 gr) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 80-90°C and stir for 2- 3 hrs. Reaction mass was heated to 135-145°C and stir for 4-6 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (200 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 86 g. Purity by HPLC: 99.8%; Formula III by HPLC: Not detected; mono amide by HPLC: 0.1% and di amide by HPLC: 0.05%. EXAMPLE-15: Purification of compound of Formula VI Compound of Formula VI (20 g; HPLC Purity: 97.5%; Formula III by HPLC: 0.9%; mono amide by HPLC: 0.5% and di amide by HPLC: 0.4%) and water (40 mL) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 50-60°C and stir for 2 hrs at same temperature. Reaction mass was cool to 25-30°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with water (10 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 39.5 g. Purity by HPLC: 99.9%; Formula III by HPLC: Not detected; mono amide by HPLC: 0.05% and di amide by HPLC: 0.05%. EXAMPLE-16: Preparation of compound of Formula VI Compound of Formula III (50 g), Urea (21.8 g) and mother liquors obtained from Ex-10; 100 mL) were added in to a round bottom flask at 25-30°C. Reaction mass was heated to 135-145°C and stir for 10-12 hrs at same temperature. After completion of the reaction, reaction mass was cool to 80-85°C and was added water (100 mL) and stir for 30 min at same temperature. Then, reaction mass was further cool to 25-35°C and stir for 4 hr at same temperature. Filtered the solids and washed the wet cake with chilled water (50 mL) and dry the wet material at 55-60°C to obtain title compound. Wt.: 41 g. Purity by HPLC: 99.6%; Formula III by HPLC: 0.15%; mono amide by HPLC: 0.1% and di amide by HPLC: 0.1%. It will be understood that various modifications may be made to the embodiments disclosed herein. Therefore the above description should not be constructed as limiting, but merely as exemplifications of preferred embodiments. For example, the functions described above and implemented as the best mode for operating the present invention are for illustration purposes only. Other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the specification appended hereto.