Field of the Invention:
The present invention provides a process for the preparation of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino] acetyl} amino)-3,3 -dimethyl butanoyl] -N-[(3S)-l-(cyclopropylamino)-l,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c] pyrrole-1-carboxamide compound represented by the following structural formula-1.
formula-1 The present invention also provides processes for the preparation of intermediates of compound of formula-1.

Background of the Invention:
(1S,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl} amino)-3,3-dimethylbutanoyl]-N-[(3S)-l-(cyclopropylamino)-l,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-1-carboxamide, commonly known as Telaprevir is an inhibitor of the HCV NS3/4A protease and is marketed under the brand names Incivek and Incivo. Telaprevir is a pharmaceutical drug co-developed by Vertex pharmaceuticals and Johnson & Johnson.

Peptidomimetic compounds useful as protease inhibitors such as Telaprevir and process for their preparation is disclosed in US7820671B2. The disclosed process is schematically represented in below scheme-A. Scheme-A:

The disclosed process involves the purification of Telaprevir as well as some of its intermediates using column chromatography. Purification of a compound using chromatography technique is a tedious process and hence not suggestible on commercial scale.

There is still a need in the art to develop an improved process for the preparation of Telaprevir. There is also a need in the art to develop an improved process for the purification of Telaprevir as well as its intermediate compounds, which avoids the usage of chromatography technique in order to make the process commercially viable.

Brief description of the Invention:
The first aspect of the present invention is to provide an improved process for the preparation of (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid compound of formula-10, which is an useful intermediate in the synthesis of compound of formula-1.

The second aspect of the present invention is to provide a process for the preparation of (lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate compound of formula-3.

The third aspect of the present invention is to provide a process for the preparation of (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24, comprising of reducing the (S)-tert-butyl l-(methoxy(methyl)amino)-l-oxopentan-2-ylcarbamate compound of formula-23 with vitride in a suitable solvent to provide (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24.

The fourth aspect of the present invention is to provide a process for the preparation of (3S)-alkyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of general formula-26, comprising of reacting the tert-butyl (2S)-l-cyano-l-hydroxypentan-2-ylcarbamate compound of formula-25 with a suitable alcohol in presence of acetyl chloride or thionyl chloride or tri(C1-C6 straight chain or branched chain)alkyl silyl halides such as trimethylsilyl chloride (TMSC1) to provide (3S)-alkyl 3-amino-2-hydroxy hexanoate hydrochloride compound of general formula-26.

The fifth aspect of the present invention is to provide a process for the preparation of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a.

The sixth aspect of the present invention is to provide a process for the preparation of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl}amino)-3,3-dimethyl butanoyl]-N-[(3S)-1 -(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxamide compound of formula-1. Brief Description of the Drawings:

Figure-1: Illustrates the PXRD pattern of crystalline form-M of (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethyl butanoic acid compound of formula-2. Figure-2: Illustrates the DSC thermogram of crystalline form-M of (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethyl butanoic acid compound of formula-2. Detailed description of the Invention:

The term "suitable solvent" used in the present invention refers to "hydrocarbon solvents" such as n-hexane, n-heptane, cyclohexane, petroleum ether, benzene, toluene, xylene and the like; "ether solvents" such as dimethyl ether, diethyl ether, methyl tert-butyl ether (MTBE), 1,2-dimethoxy ethane, tetrahydrofuran, dioxane and the like; "ester solvents" such as methyl acetate, ethyl acetate, isopropyl acetate and the like; "polar-aprotic solvents such as dimethylacetamide, dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone (NMP) and the like; "chloro solvents" such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like; "ketone solvents" such as acetone, methyl ethyl ketone, methyl isobutyl ketone and the like; "nitrile solvents" such as acetonitrile, propionitrile, isobutyronitrile and the like; "alcohol solvents" such as methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, t-butanol and the like; "polar solvents" such as water; and/or mixtures thereof.

The term "suitable base" used in the present invention refers to inorganic bases selected from "alkali metal carbonates" such as sodium carbonate, potassium carbonate, lithium carbonate and the like; "alkali metal bicarbonates" such as sodium bicarbonate, potassium bicarbonate and the like; "alkali metal hydroxides" such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; "alkali metal alkoxides" such as sodium methoxide, sodium ethoxide, potassium methoxide, sodium tert.butoxide, potassium tert.butoxide, lithium tert.butoxide; alkali metal hydrides such as sodium hydride, potassium hydride, lithium hydride; alkali metal amides such as sodium amide, potassium amide, lithium amide and the like; ammonia, alkali metal and alkaline earth metal salts of acetic acid such as sodium acetate, potassium acetate, magnesium acetate, calcium acetate and the like; and organic bases like dimethylamine, diethylamine, diisopropyl amine, diisopropylethylamine (DIPEA), diisobutylamine, triethylamine (TEA), tributylamine, pyridine, 4-dimethylaminopyridine (DMAP), N-methylmorpholine (NMM), 2,6-lutidine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), l,5-Diazabicyclo(4.3.0)non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane (DABCO), lithium diisopropylamide, imidazole; organosilicon bases such as lithium hexamethyldisilazide (LiHMDS), sodium hexamethyldisilazide (NaHMDS), potassium hexamethyldisilazide (KHMDS) and/or mixtures thereof.

The first aspect of the present invention provides an improved process for the preparation of (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid compound of formula-10, comprising of reacting the pyrazine-2-carboxylic acid compound of formula-8 with (S)-2-amino-2-cyclohexyl acetic acid compound of formula-9 in presence of a suitable coupling agent and a suitable base in a suitable solvent to provide (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid compound of formula-10.

Wherein, the suitable coupling agent is selected from but not limited to N,N'- cyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), l-ethyl-3-(3-dimethyl
aminopropyl)carbodiimide hydrochloride (EDC.HC1), N,N-carnonyldiimidazole (CDI), alkyl or
aryl chloroformates such as ethyl chloroformate, benzylchloroformate, diphenyl phosphoroazidate
(DPPA), thionyl chloride, oxalyl chloride, phosphorous oxychloride, phosphorous pentachloride, 4-
methyl-2-oxopentanoyl chloride (i-BuCOCOCl), benzotriazol-1-yl-oxytripyrrolidinophosphonium
hexafluorophosphate (PyBOP), methane sulfonyl chloride and the like optionally in combination
with l-hydroxy-7-azatriazole (HOAt), 1-hydroxy benzotriazole (HOBt), 1-hydroxy-1H-1,2,3-
triazole-4-carboxylate (HOCt), 0-(benzotriazol-1 -yl)-N,N,N',N'-tetramethyluronium
tetrafluoroborate (TBTU), N-hydroxysuccinamide (HOSu), N-hydroxy sulfosuccinimide (Sulfo-NHS), 4-dimethylaminopyridine (DMAP); the suitable base is selected from organic or inorganic bases; the suitable solvent is selected from alcohol solvents, ether solvents, ester solvents, chloro solvents or their mixtures.

A preferred embodiment of the present invention provides an improved process for the preparation of (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid compound of formula-10, comprising of reacting the pyrazine-2-carboxylic acid compound of formula-8 with (S)-2-amino-2-cyclohexylacetic acid compound of formula-9 in presence of N,N-carbonyldiimidazole (CDI), triethylamine and trimethylsilyl chloride in tetrahydrofuran to provide (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid compound of formula-10.

The second aspect of the present invention provides a process for the preparation of (lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate compound of formula-3, comprising of;
a) Chlorinating the octahydrocyclopenta[c]pyrrole hydrochloride salt compound of formula-14a with a suitable chlorinating agent in a suitable solvent to provide 2-chlorooctahydro cyclopenta[c]pyrrole compound of formula-15,
b) treating the compound of formula-15 in-situ with a suitable base in a suitable solvent optionally in presence of a suitable catalyst to provide l,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrole compound of formula-16,
c) reacting the compound of formula-16 in-situ with a suitable cyanating agent in presence of a suitable base in a suitable solvent to provide octahydrocyclopenta[c]pyrrole-l-carbonitrile compound of formula-17,
d) hydrolyzing the compound of formula-17 in-situ in presence of a suitable acid to provide octahydro cyclopenta[c]pyrrole-l-carboxylic acid compound of formula-18,

e) reacting the compound of formula-18 with di-tert.butyl dicarbonate in presence of a suitable base in a suitable solvent to provide 2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid compound of formula-19,
f) resolution of compound of formula-19 by treating it with a suitable chiral amine in a suitable solvent to provide corresponding chiral amine addition salt compound of general formula-20,
g) neutralizing the compound of general formula-20 with a suitable acid in a suitable solvent to provide (1 S,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid compound of formula-20,
h) reacting the compound of formula-20 with ethanol in presence of a suitable esterification catalyst in a suitable solvent to provide (lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate compound of formula-3,
i) optionally treating the compound of formula-3 with a suitable HC1 source to provide its hydrochloride salt compound of formula-3 a.

Wherein, in step-a) the suitable chlorinating agent is selected from sodium hypochlorite, N-chlorosuccinimide, preferably sodium hypochlorite; the suitable solvent is selected from hydrocarbon solvents, ether solvent, ester solvents, chloro solvents or mixtures thereof;

In step-b) the suitable base is selected from hydroxides, alkoxides, carbonates and bicarbonates of alkali metals; the suitable solvent is selected from hydrocarbon solvents, ether solvent, ester solvents, chloro solvents or mixtures thereof; the suitable catalyst is tetrabutyl ammonium bromide;

In step-c) the suitable cyanating agent is selected from trimethylsilyl cyanide (TMSCN), acetone cyanohydrin, alkali metal cyanides such as NaCN, KCN and the like; preferably acetone cyanohydrin; the suitable base is selected from inorganic bases, preferably sodium carbonate; the suitable solvent is selected from hydrocarbon solvents, chloro solvents, polar solvents, ether solvents, alcohol solvents, acetic acid or mixtures thereof;

In step-d) the suitable acid is selected from hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and the like and in step-e) the suitable base is selected from inorganic bases and the suitable solvent is selected from chloro solvents, ether solvents, polar solvents, hydrocarbon solvents or mixtures thereof;

In step-f) the suitable chiral amine is selected from (R)-l-phenylethanamine, (S)-1,2,3,4-tetrahydro-1-naphthylamine and the like, preferably (R)-l-phenylethanamine; the suitable solvent is selected from ester solvents, alcohol solvents, ether solvents, chloro solvents or mixtures thereof;
In step-g) the suitable acid is hydrochloric acid and the suitable solvent is selected from

chloro solvents, polar solvents, ether solvents, ester solvents or mixtures thereof; and in step-h) the suitable esterification catalyst is selected from thionyl chloride, conc.sulfuric acid; and the suitable solvent is selected from hydrocarbon solvents, ester solvents, ether solvents, chloro solvents or mixtures thereof;

In step-i) the suitable HC1 source is selected from ethyl acetate-HCl, isopropyl alcohol-HCl, ethanolic HC1 and the like.

A preferred embodiment of the present invention provides a process for the preparation of (lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate hydrochloride compound of formula-3a, comprising of;
a) Chlorinating the octahydrocyclopenta[c]pyrrole hydrochloride salt compound of formula-14a with sodium hypochlorite in toluene to provide 2-chlorooctahydro cyclopenta[c]pyrrole compound of formula-15,
b) treating the compound of formula-15 in-situ with sodium methoxide in presence of tetrabutyl ammonium bromide in dichloromethane to provide l,3a,4,5,6,6a-hexahydro cyclopenta[c]pyrrole compound of formula-16,
c) reacting the compound of formula-16 in-situ with acetone cyanohydrin in presence of aq.sodium carbonate to provide octahydrocyclopenta[c]pyrrole-l-carbonitrile of formula-17,
d) hydrolyzing the compound of formula-17 in presence of hydrochloric acid to provide octahydro cyclopenta[c]pyrrole-l-carboxylic acid compound of formula-18,
e) reacting the compound of formula-18 with di-tert.butyl dicarbonate in presence of sodium hydroxide in a mixture of water and toluene to provide 2-(tert-butoxycarbonyl)octahydro cyclopenta[c]pyrrole-l-carboxylic acid compound of formula-19,
f) resolution of compound of formula-19 with (R)-l-phenylethanamine in a mixture of ethyl acetate and isopropyl alcohol to provide (lS,3aR,6aS)-2-(tert-butoxycarbonyl)octahydro cyclopenta[c]pyrrole-l-carboxylic acid (R)-l-phenylethanamine salt of formula-20a,
g) neutralizing the compound of formula-20a with hydrochloric acid in a mixture of dichloromethane and water to provide (lS,3aR,6aS)-2-(tert-butoxycarbonyl)octahydro cyclopenta[c]pyrrole-l-carboxylic acid compound of formula-20,
h) reacting the compound of formula-20 with ethanol in presence of thionyl chloride in toluene to provide (lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate hydrochloride salt compound of formula-3a.

The third aspect of the present invention provides a process for the preparation of (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24, comprising of reducing the (S)-tert-

butyl l-(methoxy(methyl)amino)-l-oxopentan-2-ylcarbamate compound of formula-23 with vitride in a suitable solvent to provide (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24, wherein the suitable solvent is selected from hydrocarbon solvents, ester solvents, ether solvents, alcohol solvents or mixtures thereof.

A preferred embodiment of the present invention provides a process for the preparation of (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24, comprising of reducing (S)-tert-butyl l-(methoxy(methyl)amino)-l-oxopentan-2-ylcarbamate compound of formula-23 with vitride in toluene to provide (S)-tert-butyl l-oxopentan-2-ylcarbamate of formula-24.

The fourth aspect of the present invention provides a process for the preparation of (3S)-alkyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of general formula-26, comprising of reacting the tert-butyl (2S)-l-cyano-l-hydroxypentan-2-ylcarbamate compound of formula-25 with a suitable alcohol in presence of acetyl chloride or thionyl chloride or tri(C1-C6 straight chain or branched chain)alkyl silyl halides such as trimethylsilyl chloride (TMSC1) to provide (3S)-alkyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of general formula-26, wherein the suitable alcohol is of the general formula R-OH, in which the group 'R' represents C1-C6 straight chain or branched chain alkyl groups such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl and the like.

A preferred embodiment of the present invention provides a process for the preparation of (3S)-methyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of formula-26a, comprising of reacting the tert-butyl (2S)-l-cyano-l-hydroxypentan-2-ylcarbamate compound of formula-25 with methanol in presence of trimethylsilyl chloride to provide (3S)-methyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of formula-26a.

The fifth aspect of the present invention provides a process for the preparation of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a, comprising of;
a) Reacting the tert-butyl (2S)-l-cyano-l-hydroxypentan-2-ylcarbamate compound of formula-25 with a suitable alcohol in presence of acetyl chloride or thionyl chloride or tri(C1-C6 straight chain or branched chain)alkyl silyl halides such as trimethylsilyl chloride (TMSC1) to provide (3S)-alkyl 3-amino-2-hydroxy hexanoate hydrochloride salt compound of general formula-26,
b) reacting the compound of general formula-26 by reacting it in-situ with di-tert.butyl dicarbonate in presence of a suitable base in a suitable solvent to provide (3S)-alkyl 3-(tert-butoxycarbonylamino)-2-hydroxy hexanoate compound of general formula-27,
c) hydrolyzing the compound of general formula-27 in-situ in presence of a suitable base to
provide (3S)-3-(tert-butoxycarbonylamino)-2-hydroxyhexanoic acid of formula-28,

d) reacting the compound of formula-28 in-situ with cyclopropyl amine in presence of a suitable coupling agent in a suitable solvent optionally in presence of a suitable base to provide tert-butyl (3 S)-l-(cyclopropylamino)-2-hydroxy-l-oxohexan-3-ylcarbamate compound of formula-29,
e) treating the compound of formula-29 with a suitable boc-deprotecting agent in a suitable solvent to provide (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a.
Wherein, in step-a) suitable alcohol is as defined in fourth aspect of present invention;
In step-b) the suitable base and the suitable solvent are same as defined in step-e) of the second aspect of the present invention;
In step-c) the suitable base is selected from inorganic bases; the suitable solvent is selected from ether solvents, polar solvents, ester solvents, hydrocarbon solvents; ketone solvents or mixtures thereof;
In step-d) the suitable coupling agent, the suitable base and the suitable solvent are same as defined in first aspect of the present invention;
In step-e) the suitable boc-deprotecting agent is selected from ethyl acetate-HCl, isopropyl alcohol-HCl, acetyl chloride/alcohol, ethanol-HCl, methanol-HCl and the like; the suitable solvent is selected from ketone solvents, ether solvents, polar solvents, ester solvents, hydrocarbon solvents, alcohol solvents or mixtures thereof.
A preferred embodiment of the present invention provides a process for preparation of (3S)-
3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a,
comprising of;
a) Reacting the tert-butyl (2S)-l-cyano-l-hydroxypentan-2-ylcarbamate compound of formula-25 with methanol in presence of trimethylsilyl chloride to provide (3S)-methyl 3 -amino-2-hydroxy hexanoate hydrochloride salt compound of formula-26a,
b) reacting the compound of formula-26a in-situ with di-tert.butyl dicarbonate in presence of potassium carbonate in a mixture of tetrahydrofuran and water to provide (3S)-methyl 3-(tert-butoxycarbonylamino)-2-hydroxy hexanoate compound of formula-27a,
c) hydrolyzing the compound of formula-27a in-situ in presence of aq.lithium hydroxide in tetrahydrofuran to provide (3S)-3-(tert-butoxycarbonylamino)-2-hydroxyhexanoic acid compound of formula-28,
d) reacting the compound of formula-28 in-situ with cyclopropyl amine in presence of 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1)/1 -hydroxybenzotriazole
(HOBt) in a mixture of ethyl acetate and water to provide tert-butyl (3 S)-l-(cyclopropyl

amino)-2-hydroxy-l-oxohexan-3-ylcarbamate compound of formula-29, e) treating the compound of formula-29 with ethyl acetate-HCl in acetone to provide (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a.
The process disclosed in prior-art such as US7820671B2 involves the purification of Telaprevir as well as its intermediate compounds of almost all the stages using column chromatography, which is not suggestible on industrial scale.
The process of the present invention provides all the intermediate compounds as well as Telaprevir in excellent yield and purity, which is highly advantageous to the inventors. Further the high purity of the said compounds is obtained by simple isolation/crystallization techniques and doesn't involve any tedious purification processes such as chromatographic purification. Hence, the process developed by the present inventors is highly advantageous over prior known processes.
The sixth aspect of the present invention provides a process for the preparation of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl}amino)-3,3-dimethyl butanoyl]-N-[(3S)-1 -(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxarnide compound of formula-1, comprising of;
a) Reacting the (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethyl butanoic acid compound of formula-2 with (lS,3aR,6aS)-ethyl octahydrocyclopenta[c] pyrrole-1-carboxylate compound of formula-3 or its acid-addition salt, in presence of N,N'-dicyclohexyl carbodiimide (DCC)/l-hydroxybenzotriazole (HOBt) in presence of a suitable base in a suitable solvent to provide (lS,3aR,6aS)-ethyl 2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3 -dimethylbutanoyl)octahydro cyclopenta[c]pyrrole-1 -carboxylate compound of formula-4,
b) hydrolyzing the compound of formula-4 in presence of a suitable base in a suitable solvent to provide (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid compound of formula-5,
c) reacting the compound of formula-5 with (3S)-3-amino-N-cyclopropyl-2-hydroxy hexanamide compound of formula-6 or its acid-addition salt in presence of N,N'-dicyclohexyl carbodiimide (DCC)/ 1-hydroxybenzotriazole (HOBt) in presence of a suitable base in a suitable solvent to provide (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((3 S)-1 -(cyclopropylamino)-2-hydroxy-1 -oxohexan-3-yl)octahydro cyclopenta[c]pyrrole-l-carboxamide compound of formula-7,
d) oxidizing the compound of formula-7 with a suitable oxidizing agent in presence of a suitable base in a suitable solvent optionally in presence of a catalyst to provide compound of formula-1,
e) purifying the compound of formula-1 from a suitable solvent or mixture of solvents to get pure

compound of formula-1.
Wherein, in step-a) & step-c) the suitable base and the suitable solvent are same as defined in first aspect of the present invention; and in step-b) the suitable base and the suitable solvent are same as defined for step-c) of the fifth aspect of the present invention;
In step-d) the suitable oxidizing agent is selected from chromic acid, Dess-Martin periodinane (DMP), sodium hypochlorite optionally in combination with TEMPO (2,2,6,6-tetramethyl-piperidin-l-yl)oxyl), oxalyl chloride/dimethylsulfoxide (Swern oxidation), trichloroisocyanuric acid (TCICA); the suitable catalyst is NaBr, KBr and the like; the suitable solvent is selected from chloro solvents, hydrocarbon solvents, ester solvents, polar-aprotic solvents, nitrile solvents, ketone solvents or mixtures thereof;
In step-e) the suitable solvent is selected from chloro solvents, ester solvents, ether solvents, hydrocarbon solvents, polar solvents or mixtures thereof.
A preferred embodiment of the present invention provides a process for the preparation of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl}amino)-3,3-dimethyl butanoyl]-N-[(3S)-l-(cyclopropylamino)-l,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxamide compound of formula-1, comprising of;
a) Reacting the (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethyl butanoic acid compound of formula-2 with (lS,3aR,6aS)-ethyl octahydrocyclopentafc] pyrrole-1-carboxylate hydrochloride compound of formula-3a in presence of N,N'-dicyclohexylcarbodiimide (DCC)/ 1-hydroxybenzotriazole (HOBt) in presence of sodium bicarbonate in dichloromethane to provide (lS,3aR,6aS)-ethyl 2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-l-carboxylate compound of formula-4,
b) hydrolyzing the compound of formula-4 in presence of lithium hydroxide in a mixture of acetone and water to provide (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3 -dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1 -carboxylic acid compound of formula-5,
c) reacting the compound of formula-5 with (3S)-3-amino-N-cyclopropyl-2-hydroxy hexanamide hydrochloride salt compound of formula-6a in presence of N,N'-dicyclohexyl carbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) in presence of diisopropylethyl amine in dichloromethane to provide (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((3 S)-1 -(cyclopropylamino)-2-hydroxy-1 -oxohexan-3-yl)octahydro cyclopenta[c]pyrrole-l-carboxamide compound of formula-7,
d) oxidizing the compound of formula-7 with sodium hypochlorite/TEMPO in presence of sodium

bicarbonate and potassium bromide in a mixture of dichloromethane and water to provide compound of formula-1, e) purifying the compound of formula-1 from a mixture of dichloromethane and ethyl acetate to get pure compound of formula-1.
Further the present invention provides a crystalline polymorph (herein designated as form-M) of (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoic acid, which is characterized by;
a) its powder X-ray diffraction pattern having peaks at about 5.5, 7.3, 10.7, 14.7, 16.7, 17.3, 17.5, 17.8, 18.3, 19.2, 20.7, 21.4, 22.04, 22.21 & 24.7 ± 0.2 degrees of 2-theta, and
b) its powder X-ray diffraction pattern substantially in accordance with figure-1,
c) its DSC endotherm substantially in accordance with figure-2.
The compound of formula-1 is analyzed by HPLC under the following conditions; Apparatus: A liquid chromatographic system equipped with variable wavelength UV-detector and integrator; Column: X-bridge C18, 250x4.6 mm, 5μm or equivalent; Wave length: 210 nm; Flow rate: 1.0 mL/min; Column temperature: 40°C; Injection volume: 10 uL; Run time: 50 min; Diluent: acetonitrile:methanol (80:20 v/v); Elution: gradient; Buffer: Weigh accurately 3.48 gm of dipotassium hydrogen phosphate and 0.68 gm of potassium dihydrogen phosphate into 1000 ml of milli-Q-water. Adjust the pH to 8.0 with dil.KOH solution. Filtered the solution through 0.22μm Nylon membrane filter paper; Mobile phase-A: Buffer; Mobile phase-B: acetonitrile:methanol:water (300:450:250 v/v/v).
The particle size distribution of compound of formula-1 of the present invention is measured by using Malvern Mastersizer 2000 instrument.
The compound of formula-1 produced by the present invention can be further micronized or milled to get the desired particle size to achieve desired solubility profile based on different forms of pharmaceutical composition requirements. Techniques that may be used for particle size reduction include, but not limited to ball mills, roller and hammer mills and jet mills. Milling or micronization may be performed before drying or after the completion of drying of the product.
The PXRD analysis of the crystalline compound of the present invention is carried out using BRUKER/AXS X-Ray diffractometer using CuKa radiation of wavelength 1.5406 A° and at a continuous scan speed of 0.03°/min.
Differential scanning calorimetric (DSC) analysis was performed with Q10 V9.6 Build 290 calorimeter. Samples of about 2 to 3 milligrams held in a closed pan were analyzed at a heating rate of l0°C/min. The present invention is schematically represented as follows.

Wherein the group 'R' represents C1-C6 straight chain or branched chain alkyl group.
The best mode of carrying out the present invention is illustrated by the below mentioned examples. These examples are provided as illustration only and hence should not be construed as limitation to the scope of the invention.
Examples:
Example-1: Preparation of (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid
(Formula-10)
Trimethylsilyl chloride (5.15 gm) was slowly added to a pre-cooled mixture of (S)-2-amino-2-cyclohexylacetic acid compound of formula-9 (6.25 gm), tetrahydrofuran (50 ml) and triethylamine (2.3 ml) at 0-5°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 4 hrs at the same temperature. Cooled the reaction mixture to 0-5°C. Tetrahydrofuran (35 ml), pyrazine-2-carboxylic acid compound of formula-8 (5 gm) and N,N-carbonyldiimidazole (6.82 gm) were charged into another clean and dry RBF at 25-30°C and stirred the reaction mixture for 4 hrs at the same temperature. The obtained reaction mixture was slowly added to the above pre-cooled reaction mixture at 0-5°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 6 hrs at the same temperature. After completion of the reaction, water and ethyl acetate were added to the reaction mixture. Cooled the reaction mixture to 0-5°C and the pH of the reaction

mixture was adjusted to 2.5 using aqueous HC1. Both the organic and aqueous layers were separated and the organic layer was washed with water. Distilled off the solvent completely from the organic layer. To the obtained solid, water was added at 25-30°C and stirred the reaction mixture for 30 min at the same temperature. Filtered the solid and dried to get the title compound. Yield: 10.7 gm; M.R: 156-161°C; Purity by HPLC: 99.99%; Purity by chiral HPLC: 99.95%; (R)-isomer impurity: 0.05%; Specific optical rotation: +50.9° (C=1.06%, CHC13). Example-2: Preparation of (S)-methyl 2-amino-3,3-dimethylbutanoate hydrochloride (Formula-11 a)
A mixture of (S)-2-amino-3,3-dimethylbutanoic acid compound of formula-13 (100 gm) and methanol (400 ml) was heated to 40-45°C. Thionyl chloride (330 ml) was slowly added to the reaction mixture at 40-45°C. Further heated the reaction mixture to 50-5 5 °C and stirred for 18 hrs at the same temperature. After completion of the reaction, distilled off the excess thionyl chloride and methanol from the reaction mixture under reduced pressure. Dichloromethane followed by water were added to the obtained compound at 10-15°C. Basified the reaction mixture with ammonia solution and stirred for 30 min at 10-15°C. Both the organic and aqueous layers were separated and distilled off the solvent completely from the organic layer under reduced pressure. Cooled the obtained compound to 10-15°C and ethyl acetate (100 ml) was added. Adjusted the pH of the reaction mixture to 2.0 with ethyl acetate-HCl at 10-15°C and stirred for 2 hrs at the same temperature. Filtered the precipitated solid, washed with ethyl acetate and dried to get title compound; Yield: 109 gm; M.R: 158-163°C; SOR: +16.5° (C=l%, MeOH). Example-3: Preparation of (S)-methyl 2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido) acetamido)-3,3-dimethylbutanoate(Formula-12)
Imidazole (1.71 gm) and 1-hydroxybenzotriazole (1.56 gm) were added to a pre-cooled mixture of (S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetic acid compound of formula-10 (6.0 gm), dichloromethane (36 ml) and (S)-methyl 2-amino-3,3-dimethylbutanoate hydrochloride compound of formula-lla (4.96 gm) at 0-5°C. Dicyclohexylcarbodiimide solution (5.13 gm of dicyclohexylcarbodiimide dissolved in 25 ml of dichloromethane) was slowly added to the reaction mixture at 0-5°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 3 hrs at the same temperature. After completion of the reaction, filtered the reaction mixture and aqueous sodium bicarbonate solution was slowly added to the filtrate at 10-15°C and stirred for 15 min at the same temperature. Both the organic and aqueous layers were separated and aqueous hydrochloric acid solution was added to the organic layer at 10-15°C and stirred the reaction mixture for 20 min at the same temperature. Both the organic and aqueous layers were separated and the organic layer was washed with water. Distilled off the solvent completely from the organic

layer under reduced pressure. Methyl tert.butyl ether (36 ml) was added to the obtained compound at 25-30°C and stirred the reaction mixture for 1 hr at the same temperature. Filtered the solid and dried to get the title compound.
Yield: 8.5 gm; M.R: 180-185°C; Purity by HPLC: 99.83%; SOR: -2.0° (C=l%, CHC13). Example-4: Preparation of (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoic acid (Formula-2)
Lithium hydroxide solution (2.4 gm of LiOH.H2O dissolved in 37.5 ml of water) was slowly added to a pre-cooled solution of (S)-methyl 2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido) acetamido)-3,3-dimethylbutanoate compound of formula-12 (7.5 gm) in acetone (37.5 ml) at 10-15°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 8 hrs at the same temperature. After completion of the reaction, water followed by toluene were added to the reaction mixture at 25-30°C and stirred for 10 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was cooled to 10-15°C. Adjusted the pH of the aqueous layer to 2.5 at 10-15°C using aq.HCl solution and stirred the reaction mixture for 1 hr at the same temperature. Filtered the precipitated solid and washed with water. Methyl tert.butyl ether (60 ml) was added to the obtained solid at 25-30°C, heated the reaction mixture to 50-55°C and stirred for 1 hr at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 1 hr at the same temperature. Filtered the solid and dried to get the title compound. The PXRD pattern of the obtained compound is shown in figure-1; Yield: 7.0 gm; M.R: 184-186°C; Purity by HPLC: 99.9%; Purity by chiral HPLC: 99.88%; SR isomer: 0.02%; RS isomer: 0.03%; Specific optical rotation: +21.7° (C=1.015%, CHC13); MTBE content: 9.5%.
Example-5: Preparation of octahydrocyclopenta[c]pyrrole-l-carbonitrile hydrochloride (Formula-17a)
13% Sodium hypochlorite solution (1552 ml) was slowly added to a solution of octahydrocyclopenta[c]pyrrole hydrochloride compound of formula-14a (200 gm) in toluene (1000 ml) at 25-3 0°C and stirred the reaction mixture for 2 hrs at the same temperature. After completion of the reaction, both the organic and aqueous layers were separated. Anhydrous sodium methoxide (151.8 gm) was added to the organic layer at 25-30°C. Slowly added tetrabutyl ammonium bromide solution (4.4 gm of terra butyl ammonium bromide dissolved in 200 ml of dichloromethane) to the reaction mixture at 25-30°C. Heated the reaction mixture to 40-45°C and stirred for 8 hrs at the same temperature. Water was added to the reaction mixture at 25-30°C and stirred for 15 min at the same temperature. Both the organic and aqueous layers were separated and aqueous sodium carbonate solution (360 gm of sodium carbonate in 1400 ml of water) was added to the organic layer at 25-30°C. Acetone cyanohydrin (230 gm) was slowly added to the reaction mixture at 25-

30°C and stirred for 12 hrs at the same temperature. After completion of the reaction, both the organic and aqueous layers were separated and the pH of the organic layer was adjusted to below 3.0 using dil.hydrochloric acid solution at 10-15°C. Both the organic and aqueous layers were separated and dichloromethane was added to the aqueous layer. Basified the reaction mixture using 25% NaOH solution at 5-10°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 20 min at the same temperature. Both the organic and aqueous layers were separated and distilled off the solvent completely from the organic layer under reduced pressure. Ethyl acetate (600 ml) was added to the obtained compound. Ethyl acetate-HCl (600 ml) was added to the reaction mixture at 25-30°C and stirred for 2 hrs at the same temperature. Filtered the precipitated solid and dried to get the title compound. Yield: 160.0 gm; M.R: 160-165°C. Example-6: Preparation of 2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid (Formula-19)
A mixture of conc.HCl (420 ml) and octahydrocyclopenta[c]pyrrole-l-carbonitrile hydrochloride compound of formula-17a (140 gm) was heated to 60-65°C and stirred for 4 hrs at the same temperature. Another 280 ml of conc.HCl was added to the reaction mixture at 60-65°C and stirred for 10 hrs at the same temperature. After completion of the reaction, distilled off the reaction mixture completely under reduced pressure. Water (980 ml) was added to the obtained compound at 25-30°C. Sodium hydroxide solution (162 gm of NaOH in 420 ml of water) was slowly added to the reaction mixture at 25-30°C. A solution of di-tert.butyl dicarbonate (265 gm) in toluene (700 ml) was slowly added to the reaction mixture at 25-30°C and stirred for 10 hrs at the same temperature. After completion of the reaction, both the organic and aqueous layers were separated and dichloromethane was added to the aqueous layer at 25-3 0°C. Cooled the reaction mixture to 0-5°C and adjusted the pH of the reaction mixture to 2.0 using 5N HC1 solution and stirred for 20 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane at 0-5°C. The combined organic layer was washed with water and distilled off the solvent completely from the organic layer under reduced pressure to get the title compound; Yield: 165.0 gm.
Example-7: Preparation of (lS,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c] pyrrole- 1-carboxylic acid (R)-l-phenylethanamine salt (Formula-20a)
(R)-l-phenylethanamine (88.5 gm) was slowly added to a solution of 2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid compound of formula-19 obtained in example-6 in isopropyl alcohol (280 ml) and ethyl acetate (1400 ml) at 25-30°C and stirred the reaction mixture for 8 hrs at the same temperature. Filtered the precipitated solid and washed with ethyl acetate. Isopropyl alcohol (70 ml) and ethyl acetate (1120 ml) were added to the

!
obtained solid at 25-3 0°C and stirred for 8 hrs at the same temperature. Filtered the solid, washed with ethyl acetate and dried to get the title compound. Yield: 80.0 gm.
ExampIe-8: Preparation of (lS,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocycIopenta[c] pyrrole-l-carboxylic acid (Formula-20)
Dichloromethane (980 ml) and water (700 ml) were added to (R)-l-phenylethanamine salt compound of formula-20a (80 gm) and cooled the reaction mixture to 0-5°C. Adjusted the pH of the reaction mixture to 2.0-2.5 using 5N HC1 solution at 0-5°C and stirred the reaction mixture for 20 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water. Distilled off the solvent completely from the organic layer under reduced pressure and co-distilled with n-heptane. Water (420 ml) was added to the obtained solid at 25-30°C and stirred for 45 min at the same temperature. Filtered the solid, washed with water and dried to get the title compound. Yield: 50.0 gm.
Example-9: Preparation of (lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate hydrochloride (Formula-3a)
(lS,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid
compound of formula-20 (100 gm) was added to a mixture of toluene (500 ml) and ethanol (200 ml) at 25-30°C. Thionyl chloride (56.7 ml) was slowly added to the reaction mixture at 25-30°C and stirred for 90 min at the same temperature. Heated the reaction mixture to 60-65°C and stirred for 8 hrs at the same temperature. After completion of the reaction, distilled off the excess thionyl chloride completely under reduced pressure and co-distilled the reaction mixture with toluene. 300 ml of toluene was added to the obtained compound at 60-65°C and stirred for 2 hrs at the same temperature. Cooled the reaction mixture to 25-3 0°C and stirred for 2 hrs at the same temperature. Filtered the precipitated solid, washed with toluene under N2 atmosphere and dried to get the title compound. Yield: 69.0 gm. Example-10: Preparation of (S)-2-(tert-butoxycarbonylamino)pentanoic acid (Formula-22)
(S)-2-aminopentanoic acid compound of formula-21 (200 gm) was added to aqueous sodium carbonate solution (453 gm of sodium carbonate in 2000 ml of water) at 25-30°C. Di-tert.butyl dicarbonate (484 gm) was added to the reaction mixture at 20-25°C and stirred the reaction mixture for 8 hrs at same temperature. After completion of the reaction, cooled the reaction mixture to 0-5°C, dichloromethane was added and stirred for 10 min at the same temperature. Adjusted the pH of the reaction mixture to 2-3 using aqueous HC1 solution at 0-5°C. Both the organic and aqueous layers were separated and the aqueous layer was extracted with

dichloromethane. Combined the organic layers and washed with water. Distilled off the solvent
completely from the organic layer to get the title compound. Yield: 352.0 gm.
Example-11: Preparation of tert-butyl (2S)-l-cyano-l-hydroxypentan-2-yIcarbamate
(Formula-25)
Step-a): Preparation of (S)-tert-butyl l-(methoxy(methyI)amino)-l-oxopentan-2-yI carbamate
Toluene (740 ml) was added to N,N-carbonyldiimidazole (331 gm) at 25-30°C and cooled the reaction mixture to 0-5°C. A solution of (S)-2-(tert-butoxycarbonylamino)pentanoic acid compound of formula-22 (435 gm) in toluene (370 ml) was added to the reaction mixture at 0-5°C and stirred for 3 hrs at the same temperature. N,0-dimethylhydroxylamine hydrochloride (265 gm) and diisopropylethyl amine (356 ml) were added to the reaction mixture at 0-5°C and stirred for 3 hrs at the same temperature. After completion of the reaction, water was added to the reaction mixture. Both the organic and aqueous layers were separated and the aqueous layer was extracted with toluene. Combined the organic layers and washed with aq.HCl followed by 10% aq.sodium bicarbonate solution. The obtained organic layer containing (S)-tert-butyl 1-(methoxy(methyl)amino)-l-oxopentan-2-yl carbamate compound of formula-23 was utilized in the next step without isolating the product from the reaction mixture. Step-b): Preparation of (S)-tert-butyl l-oxopentan-2-yIcarbamate
70% vitride solution (830 ml) was added to the organic layer obtained in the step-a) at -15° to -10°C and stirred the reaction mixture for 45 min at the same temperature. The reaction mixture was slowly added to pre-cooled aq. sodium potassium tartrate solution (856 gm of sodium potassium tartrate in 1688 ml of water) was slowly added to the reaction mixture at 0-5°C. Raised the temperature of the reaction mixture to 20-25°C and stirred for 20 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with toluene. The combined organic layer was washed with 10% aqueous sodium chloride solution. The obtained organic layer containing (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24 was utilized in the next step without isolating the product from the reaction mixture. Step-c): Preparation of tert-butyl (2S)-l-cyano-l-hydroxypentan-2-yI carbamate
The organic layer containing (S)-tert-butyl 1 -oxopentan-2-ylcarbamate which is obtained in step-b) was added to aqueous sodium carbonate solution (435 gm of sodium carbonate in 2110 ml of water) at 25-3 0°C. Acetone cyanohydrin (300 ml) was slowly added to the reaction mixture at 25-30°C and stirred for 2 hrs at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was extracted with toluene. The combined organic layer was washed with water. Distilled off the solvent completely from the organic layer under reduced pressure to get the title compound. Yield: 350 gm.

Example-12: Preparation of tert-butyl (3S)-l-(cyclopropylamino)-2-hydroxy-l-oxo hexan-3-yI
carbamate (FormuIa-29)
Step-a): Preparation of (3S)-methyl 3-amino-2-hydroxyhexanoate hydrochloride
Trimethylsilyl chloride (773 ml) was added to a mixture of tert-butyl (2S)-l-cyano-l-hydroxypentan-2-yl carbamate compound of formula-25 (345 gm) and methanol (1725 ml) at 25-30°C. Heated the reaction mixture to 50-55°C and stirred for 5 hrs at the same temperature. Cooled the reaction mixture to 0-5°C and filtered the reaction mixture. Distilled off the solvent completely from the filtrate. Water and dichloromethane were added to the obtained compound and stirred for 15 min. Both the organic and aqueous layers were separated and the aqueous layer was washed with dichloromethane. The obtained aqueous layer containing (3S)-methyl 3-amino-2-hydroxyhexanoate hydrochloride was utilized in the next step without isolating the product from the reaction mixture. Step-b): Preparation of (3S)-methyl 3-(tert-butoxycarbonyIamino)-2-hydroxyhexanoate
Potassium carbonate (410 gm) and tetrahydrofuran (1035 ml) were added to the aqueous layer obtained in step-a) at 10-15°C. Di-tert.butyl dicarbonate (329 gm) was slowly added to the reaction mixture at 10-15°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 6 hrs at the same temperature. After completion of the reaction, water was added to the reaction mixture and stirred for 15 min. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane. Combined the organic layers and washed with 5% aq.sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure to get the title compound. Yield: 345 gm. Step-c): Preparation of (3S)-3-(tert-butoxycarbonyIamino)-2-hydroxyhexanoic acid
Aq.LiOH solution (164 gm of LiOH in 862 ml of water) was added to a solution of (3S)-methyl 3-(tert-butoxycarbonylamino)-2-hydroxyhexanoate compound of formula-27a (345 gm) in tetrahydrofuran (1725 ml) at 0-5°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 8 hrs at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was cooled to 0-5°C. Distilled off the solvent completely from organic layer, water and above cooled aqueous layer were added to the obtained residue. Toluene was added to the reaction mixture at 25-30°C and stirred for 15 min at the same temperature. Both the organic and aqueous layers were separated and the aqueous layer was washed with toluene. Dichloromethane was added to the aqueous layer and cooled the reaction mixture to 0-5°C. Acidified the reaction mixture with aq.hydrochloric acid solution. Both the organic and aqueous layers were separated and the aqueous layer was extracted with dichloromethane. Combined the organic layers and washed with 5% aq.sodium chloride solution. Distilled off the solvent completely from the organic layer under reduced pressure to get the title compound. Yield: 270 gm.

Step-d): Tert-butyl (3S)-l-(cyclopropyIamino)-2-hydroxy-l-oxohexan-3-yI carbamate (Formula-29)

Ethyl acetate (2700 ml) and water (270 ml) were added to (3S)-methyl 3-(tert-butoxy carbonylamino)-2-hydroxyhexanoate compound of formula-28 (270 gm) obtained in step-c) at 25-30°C. Cooled the reaction mixture to 0-5°C. 1-hydroxybenzotriazole (147.5 gm) and l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (251 gm) were added to the reaction mixture at 0-5°C. Cyclopropyl amine (87.2 gm) was added to the reaction mixture at 0-5°C and stirred for 2 hrs at the same temperature. After completion of the reaction, ethyl acetate (1350 ml) and 5% aqueous sodium bicarbonate solution (40.5 gm of sodium bicarbonate in 810 ml of water) were added to the reaction mixture. Heated the reaction mixture to 40-45°C and stirred for 15 min at the same temperature. Both the organic and aqueous layers were separated and 5% sodium chloride solution was added to the organic layer. Heated the reaction mixture to 40-45 °C and stirred for 10 min at the same temperature. Both the organic and aqueous layers were separated and distilled off the solvent completely from the organic layer and co-distilled with pet ether under reduced pressure. To the obtained solid, pet ether (810 ml) and ethyl acetate (270 ml) were added. Heated the reaction mixture to 55-60°C and stirred for 1 hr at the same temperature. Slowly cooled the reaction mixture to 0-5°C and stirred for 2 hrs at the same temperature. Filtered the precipitated solid, washed with pet ether followed by ethyl acetate and dried to get the title compound. Yield: 232.0 gm.
Example-13: Preparation of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide
hydrochloride (Formula-6a)

Ethyl acetate-HCl (636 ml) was added to a mixture of tert-butyl (3S)-l-(cyclopropylamino)-2-hydroxy-l-oxohexan-3-yl carbamate compound of formula-29 (100 gm) and acetone (500 ml) at 25-30°C and stirred the reaction mixture for 8 hrs at the same temperature. Filtered the precipitated solid, washed with a mixture of acetone and ethyl acetate and dried the material to get the title compound. Yield: 60 gm; M.R: 165-170°C.

Example-14: Preparation of (lS,3aR,6aS)-ethyl 2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethyIbutanoyl)octahydrocyclopenta[c]pyrrole-l-carboxylate (Formula-4)

(lS,3aR,6aS)-ethyl octahydrocyclopenta[c]pyrrole-l-carboxylate hydrochloride compound of formula-3a (1.75 gm) was added to a mixture of sodium bicarbonate (0.85 gm) and water (2.5 ml) at 25-30°C and stirred for 30 min at the same temperature. Dichloromethane (25 ml) was added to the reaction mixture at 25-30°C and stirred for 15 min at the same temperature. Both the organic and aqueous layers were separated and the organic layer was dried over sodium sulfate. (S)-2-((S)-

2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoic acid compound of formula-2 (2.5 gm) was added to the organic layer at 25-30°C. Cooled the reaction mixture to 0-5°C, 1-hydroxybenotriazole (0.45 gm) and a solution of N,N-dicyclohexylcarbodiimide (1.5 gm) in dichloromethane (10 ml) were added. Raised the temperature of the reaction mixture to 25-30°C and stirred for 4 hrs at the same temperature. After completion of the reaction, filtered the reaction mixture and washed the filtrate with dichloromethane, sodium bicarbonate solution followed by conc.HCl solution. Water was added to the filtrate at 25-30°C and stirred for 20 min at the same temperature. Both the organic and aqueous layers were separated, distilled off the solvent completely from the organic layer to get the title compound.

Example-15: Preparation of (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid (Formula-5)

Acetone (15 ml) was added to (lS,3aR,6aS)-ethyl 2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3 -dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1 -carboxylate compound of formula-4 obtained in example-14 at 25-30°C and stirred for 10 min at the same temperature. Cooled the reaction mixture to 10-15°C and lithium hydroxide solution (0.42 gm of lithium hydroxide hydrate in 15 ml of water) was slowly added. Raised the temperature of the reaction mixture to 25-30°C and stirred for 6 hrs at the same temperature. After completion of the reaction, water and toluene were added to the reaction mixture at 25-3 0°C and stirred for 20 min at the same temperature. Both the organic and aqueous layers were separated and dichloromethane was added to the aqueous layer. Cooled the reaction mixture to 10-15 °C and the pH of the reaction mixture was adjusted to 2-3 using conc.HCl solution. Stirred the reaction mixture for 20 min at 10-15°C and both the organic and aqueous layers were separated. Extracted the aqueous layer with dichloromethane and the combined organic layer was washed with water. Distilled off the solvent completely from the organic layer. Toluene was added to the reaction mixture at 35-40°C, heated the reaction mixture to 70-75°C and stirred for 90 min at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 6 hrs at the same temperature. Filtered the obtained solid, washed with methyl tertbutyl ether and dried to get the title compound. Yield: 2.2 gm. Example-16: Preparation of (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((3S)-l-(cyclopropylamino)-2-hydroxy-l-oxohexan-3-yI)octahydrocyclopenta[c]pyrrole-l-carboxamide(Formula-7)

1-hydroxybenzotriazole (13.2 gm) and (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride compound of formula-6a (47.7 gm) were added to a pre-cooled mixture of (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido) acetamido)-3,3-dimethyl

butanoyl)octahydrocyclopenta[c]pyrrole-l-carboxylic acid compound of formula-5 (100 gm) and dichloromethane (800 ml) at 0-5°C. Diisopropylethylamine (30.2 gm) and N,N-dicyclohexyl carbodiimide solution (44.2 gm of N,N-dicyclohexylcarbodiimide in 200 ml of dichloromethane) were slowly added to the reaction mixture at 0-5°C. Raised the temperature of the reaction mixture to 25-30°C and stirred for 4 hrs at the same temperature. After completion of the reaction, filtered the reaction mixture and washed the filtrate with sodium bicarbonate solution, aq.hydrochloric acid solution followed by water. Distilled off the solvent completely from the obtained organic layer. Ethyl acetate (900 ml) was added to the obtained compound at 25-30°C and stirred for 1 hr at the same temperature. Filtered the reaction mixture through hyflow bed and washed with ethyl acetate. Distilled off the solvent completely from the filtrate and co-distilled with cyclohexane. 500 ml of cyclohexane was added to the obtained solid at 25-30°C and stirred for 1 hr at the same temperature. Filtered the solid and dried to get the title compound. Yield: 120.0 gm; M.R: 113-118°C; Purity by HPLC: 94.84%.

Example-17: Preparation of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-yl carbonyI)ainino]acetyl}amino)-3,3-dimethylbutanoyl]-N-[(3S)-l-(cyclopropylainino)-l,2-di oxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxamide (Formula-1) 0.45 gm of 2,2,6,6-tetramethyl-piperidin-l-yl)oxyl (TEMPO) was slowly added to a pre-cooled mixture of (lS,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido) acetamido)-3,3-dimethylbutanoyl)-N-((3 S)-1 -(cyclopropylamino)-2-hydroxy-1 -oxohexan-3 -yl) octahydrocyclopenta[c]pyrrole-l-carboxamide compound of formula-7 (100 gm) and dichloromethane (1000 ml) at 0-5°C and stirred the reaction mixture for 15 min at the same temperature. Potassium bromide (3.4 gm) was added to the reaction mixture at 0-5°C and the reaction mixture was kept aside. Aqueous sodium bicarbonate solution was slowly added to pre-cooled 13% sodium hypochlorite solution (100 ml) in another RBF at 5-10°C and stirred for 30 min at the same temperature. The resulting solution was slowly added to the above reaction mixture at 0-5°C and stirred for 45 min at the same temperature. After completion of the reaction, both the organic and aqueous layers were separated. Sodium sulfite solution was slowly added to the organic layer at 10-15°C and stirred for 30 min at the same temperature. Both the organic and aqueous layers were separated and the organic layer was washed with water. Carbon (10 gm) was added to the organic layer and stirred for 15 min. Filtered the reaction mixture through hyflow bed and distilled off the solvent completely from the filtrate and co-distilled with cyclohexane. Ethyl acetate (300 ml) was added to the obtained solid at 25-30°C and stirred for 1 hr at the same temperature. Filtered the solid and dried to get the title compound. Yield: 82.0 gm; M.R: 230-235°C; Purity by HPLC: 97.41%; Specific optical rotation: -48.0° (C=l%, CHC13).

Particle size distribution: D(0.1) is 4.24, D(0.5) is 44.69 and D(0.9) is 95.97.
Example-18: Purification of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-yl
carbonyl)amino]acetyl}amino)-3,3-dimethylbutanoyl]-N-[(3S)-l-(cydopropyIainino)-l,2-di
oxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxamide (Formula-1)

Aq.sodium bisulfite solution (1.14 gm of sodium bisulfite dissolved in 50 ml of water) was added to a pre-cooled solution of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-yl carbonyl)amino]acetyl}amino)-3,3-dimethylbutanoyl]-N-[(3S)-l-(cyclopropylamino)-l,2-dioxo hexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l -carboxamide compound of formula-1 (5 gm) in dichloromethane (50 ml) at 10-15°C and stirred the reaction mixture for 30 min at the same temperature. Both the organic and aqueous layers were separated, Dichloromethane was added to the aqueous layer and cooled the reaction mixture to 10-15°C. 50% glyoxalic acid solution was slowly added to the reaction mixture at 10-15°C. Raised the temperature of the reaction mixture to 25-3 0°C and stirred for 2 hrs at the same temperature. Both the organic and aqueous layers were separated, distilled off the solvent completely from the organic layer and co-distilled with ethyl acetate. To the obtained solid, ethyl acetate (20 ml) was added at 25-30°C and stirred the reaction mixture for 30 min at the same temperature. Filtered the solid, washed with ethyl acetate and dried to get the pure title compound; Yield: 3.5 gm; Purity by HPLC: 98.96%. Particle size distribution: D(0.1) is 14.31 urn, D(0.5) is 38.80 urn and D(0.9) is 66.98 urn. Example-19: Purification of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-yl carbonyl)amino]acetyl}amino)-3,3-dimethylbutanoyl]-N-[(3S)-l-(cyclopropylaniino)-l,2-di oxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxamide (Formula-1)

A mixture of dichloromethane (200 ml) and (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino] acetyl} amino)-3,3 -dimethylbutanoyl] -N-[(3 S)-1 -(cyclopropylamino) -1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-1 -carboxamide compound of formula-1 (100 gm) was stirred for 10 min at 25-30°C. Heated the reaction mixture to 40-45°C and ethyl acetate (500 ml) was slowly added. Further heated the reaction mixture to 65-70°C and stirred for 2 hrs at the same temperature. Cooled the reaction mixture to 25-30°C and stirred for 4 hrs at the same temperature. Filtered the precipitated solid and dried to get the title compound. Yield: 82.0 gm; Purity by HPLC: 99.90%; Hydroxy impurity (compound of formula-8): 0.01%; Metabolite impurity ((R)-diastereomer): 0.05%.

Particle size distribution: D(0.1) is 10.83 μm, D(0.5) is 64.65 urn and D(0.9) is 151.23 urn. Particle size distribution (after pulverization): D(0.1) is 1.37 μm, D(0.5) is 6.60 urn and D(0.9) is 21.62 μm.

We Claim:
1. A process for the preparation of (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24, comprising of reducing the (S)-tert-butyl l-(methoxy(methyl)amino)-l-oxopentan-2-ylcarbamate compound of formula-23 with vitride in a suitable solvent to provide (S)-tert-butyl l-oxopentan-2-ylcarbamate compound of formula-24, wherein the suitable solvent is selected from hydrocarbon solvents, ester solvents, ether solvents, alcohol solvents, ketone solvents, polar solvents, chloro solvents or their mixtures.

2. A process for the preparation of (S)-tert-butyl 1 -oxopentan-2-ylcarbamate compound of formula-24, comprising of reducing the (S)-tert-butyl 1-(methoxy(methyl)amino)-1-oxopentan-2-ylcarbamate compound of formula-23 with vitride in toluene to provide (S)-tert-butyl 1-oxopentan-2-ylcarbamate compound of formula-24.

3. A process for the preparation of (3S)-alkyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of general formula-26, comprising of reacting the tert-butyl (2S)-1-cyano-1-hydroxypentan-2-ylcarbamate compound of formula-25 with a suitable alcohol in presence of acetyl chloride or thionyl chloride or tri(C1-C6 straight chain or branched chain)alkyl silyl halides such as trimethylsilyl chloride (TMSC1) to provide (3S)-alkyl 3-amino-2-hydroxy hexanoate hydrochloride salt compound of general formula-26.

4. The process according to claim 3, wherein the suitable alcohol is of the general formula R-OH in which the group 'R' represents C1-C6 straight chain or branched chain alkyl group.

5. A process for the preparation of (3S)-methyl 3-amino-2-hydroxyhexanoate hydrochloride salt compound of formula-26a, comprising of reacting the tert-butyl (2S)-1-cyano-1-hydroxypentan-2-ylcarbamate compound of formula-25 with methanol in presence of trimethylsilyl chloride to provide (3S)-methyl 3-amino-2-hydroxyhexanoate hydrochloride compound of formula-26a.

6. A process for the preparation of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a, comprising of;

a) Reacting the tert-butyl (2S)-1-cyano-l-hydroxypentan-2-ylcarbamate compound of formula-25 with a suitable alcohol in presence of acetyl chloride or thionyl chloride or tri(C1-C6 straight chain or branched chain)alkyl silyl halides such as trimethylsilyl chloride (TMSC1) to provide (3S)-alkyl 3-amino-2-hydroxy hexanoate hydrochloride salt compound of general formula-26,
b) reacting the compound of general formula-26 by reacting it in-situ with di-tert.butyl dicarbonate in presence of a suitable base in a suitable solvent to provide (3S)-alkyl 3-(tert-butoxy carbonylamino)-2-hydroxy hexanoate compound of general formula-27,
c) hydrolyzing the compound of general formula-27 in-situ in presence of a suitable base to provide (3S)-3-(tert-butoxycarbonylamino)-2-hydroxyhexanoic acid compound of formula-28,
d) reacting the compound of formula-28 in-situ with cyclopropyl amine in presence of a suitable coupling agent in a suitable solvent optionally in presence of a suitable base to provide tert-butyl (3S)-1 -(cyclopropylamino)-2-hydroxy-1 -oxohexan-3 -ylcarbamate compound of formula-29,
e) treating the compound of formula-29 with a suitable boc-deprotecting agent in a suitable solvent to provide (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a.

7. The process according to claim 6, wherein in
step-a) the suitable alcohol is of the general formula R-OH in which the group 'R' represents C1-C6 straight chain or branched chain alkyl group;
in step-b) the suitable base is selected from inorganic bases and the suitable solvent is selected from chloro solvents, ether solvents, polar solvents, hydrocarbon solvents or their mixtures;
in step-c) the suitable base is inorganic base; the suitable solvent is selected from ether solvents, polar solvents, ester solvents, hydrocarbon solvents, ketone solvents or their mixtures;
in step-d) the suitable coupling agent is selected from but not limited to N,N'-dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC.HC1), N,N-carnonyldiimidazole (CDI), alkyl or aryl chloroformates such as ethyl chloroformate, benzylchloroformate, thionyl chloride, oxalyl chloride, benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), methane sulfonyl chloride and the like optionally in combination with l-hydroxy-7-azatriazole (HOAt), 1-hydroxybenzotriazole (HOBt), O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), N-hydroxy succinimide (HOSu); the suitable base is selected from organic or inorganic bases; the suitable solvent is selected from alcohol solvents, ether solvents, ester solvents, chloro solvents, hydrocarbon solvents or their mixtures;
in step-e) the suitable boc-deprotecting agent is selected from ethyl acetate-HC1, isopropyl alcohol-HC1, acetyl chloride/alcohol, ethanol-HC1, methanol-HC1 and the like; the suitable solvent is selected from ketone solvents, ether solvents, polar solvents, ester solvents, hydrocarbon solvents, alcohol solvents or mixtures thereof.

8. A process for the preparation of (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride salt compound of formula-6a, comprising of;
a) Reacting the tert-butyl (2S)-1-cyano-1-hydroxypentan-2-ylcarbamate compound of formula-25 with methanol in presence of trimethylsilyl chloride (TMSC1) to provide (3S)-methyl 3-amino-2-hydroxy hexanoate hydrochloride compound of formula-26a,
b) reacting the compound of formula-26a by reacting it in-situ with di-tert.butyl dicarbonate in presence of potassium carbonate in a mixture of tetrahydrofuran and water to provide (3S)-methyl 3-(tert-butoxycarbonylamino)-2-hydroxy hexanoate compound of formula-27a,
c) hydrolyzing the compound of formula-27a in-situ in presence of aq.lithium hydroxide in tetrahydrofuran to provide (3S)-3-(tert-butoxycarbonylamino)-2-hydroxyhexanoic acid compound of formula-28,
d) reacting the compound of formula-28 in-situ with cyclopropyl amine in presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HC1)/1 -hydroxy benzotriazole (HOBt) in a mixture of ethyl acetate and water to provide tert-butyl (3S)-1-(cyclopropyl amino)-2-hydroxy-1-oxohexan-3-ylcarbamate compound of formula-29,
e) treating the compound of formula-29 with ethyl acetate-HC1 in acetone to provide (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride compound of formula-6a.

9. A process for the preparation of (lS,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl}amino)-3,3-dimethyl butanoyl]-N-[(3S)-l-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrole-l-carboxamide compound of formula-1, comprising of;
a) Reacting the (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoic acid compound of formula-2 with (1S,3aR,6aS)-ethyl octahydro cyclopenta[c]pyrrole-1-carboxylate hydrochloride compound of formula-3a in presence of N,N'-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) in presence of sodium bicarbonate in dichloromethane to provide (1S,3aR,6aS)-ethyl 2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydro cyclopenta[c]pyrrole-1-carboxylate compound of formula-4,
b) hydrolyzing the compound of formula-4 in presence of aq.LiOH in acetone to provide (1 S,3 aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido) acetamido)-3,3 -dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1 -carboxylic acid of formula-5,
c) reacting the compound of formula-5 with (3S)-3-amino-N-cyclopropyl-2-hydroxy hexanamide hydrochloride salt compound of formula-6a in presence of N,N'-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) and diisopropylethyl amine in dichloromethane to provide (1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((3S)-1-(cyclopropyl aminos-hydroxy- 1 -oxohexan-3 -yl)octahydrocyclopenta[c]pyrrole-1 -carboxamide compound of formula-7,
d) oxidizing the compound of formula-7 with sodium hypochlorite/TEMPO in presence of sodium bicarbonate and potassium bromide in a mixture of dichloromethane and water to provide compound of formula-1,
e) purifying the compound of formula-1 from a mixture of dichloromethane and ethyl acetate to get pure compound of formula-1.

10. Crystalline form-M of (S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoic acid, characterized by;
a) its powder X-ray diffraction pattern having peaks at about 5.5, 7.3, 10.7, 14.7, 16.7, 17.3, 17.5,17.8, 18.3, 19.2, 20.7, 21.4, 22.04, 22.21 & 24.7 ± 0.2 degrees of 2-theta, and
b) its powder X-ray diffraction pattern substantially in accordance with figure-1,
c) its DSC endotherm substantially in accordance with figure-2.