DESC:“IMPROVED PROCESS FOR 2-((1R,4R)-4-((TERT-BUTOXYCARBONYL) AMINO) CYCLOHEXYL) ETHYL METHANE SULFONATE”

FIELD OF THE INVENTION

The present invention relates to an improved process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate, which is used key intermediate for the preparation of Cariprazine Hydrochloride.

BACKGROUND OF THE INVENTION
Cariprazine Hydrochloride, which was approved in US under the brand name of VRAYLAR®, which is chemically known as trans-N- {4- [2- [4-(2,3-dichloro phenyl) piperazine-1-yl] ethyl] cyclohexyl}-N’, N’-dimethylurea hydrochloride. The molecular formula is C21H33Cl3N4O, and the molecular weight is 463.9 g/mol. The structural formula is:

Cariprazine is an atypical antipsychotic which is used in the treatment of schizophrenia, bipolar mania and bipolar depression. It is also potentially useful as an add-on therapy in major depressive disorder.

Major synthetic process of Cariprazine HCl utilizes the below key intermediates i.e. 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I).

Cariprazine was first reported in US 7737142 of Richter Gedeon Vegyeszeti Gyar Rt.
US 7875715 discloses process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), which comprises tert-butyl [1-(2-hydroxyethyl) cyclohexyl-4-yl] carbamate is reacted with methanesulfonyl chloride in presence of TEA and MDC to obtain the crude 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), which was used without purification for the next step, and the following structural formula.

The disadvantage of the aforementioned prior art process without purification can result in the presence of unwanted impurities, leading to a lower purity.

US 8,569,496 discloses process of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), which comprises trans 2-[1-(4-amino]-cyclohexyl)-acetic acid ethyl ester hydrochloride (V) is reacted with di(tert-butyl) dicarbonate in presence of TEA and MDC to get trans 2-{1-[4-(N-tert-butoxycarbonyl)-amino]-cyclohexyl}-acetic acid ethyl ester (VI), which is undergoes reduction in presence of NaBH4 / THF to get trans 2-{1-[4-(N-tert-butoxycarbonyl)-amino]-cyclohexyl} ethanol (VII). Further, which is reacted with methanesulfonyl chloride in presence of TEA/MDC to get 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), and the following structural formula.

The disadvantage of the aforementioned prior art process in step-ii) and step-iii) conditions may lead to the presence of impurities like unreacted starting materials of compound (VI) in the final product compound. The main drawback in the reaction step-ii) is, after adjusted the reaction mass pH to 4.5-5.5 with hydrochloric acid, the reaction maintenance up to ~20% unreacted was remained in the reaction mass. By maintained the reaction mass for long time, there is no change in the conversion of the reaction was observed.

The presence of these impurities may depend on the solvent, reaction conditions. None of the above noted documents mentions suitable conditions to avoid the formation of impurities, or purification techniques to reduce those impurities.

Hence, there is a need to develop a purification process, which removes the unreacted intermediate compound from the reaction mass, which in turn provides highly pure compound of tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII).

SUMMARY OF THE INVENTION

The present invention relates to an improved process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate, which is used key intermediate for the preparation of Cariprazine Hydrochloride.

In one aspect of the present invention provides a process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), comprising the steps of:
a) reacting compound of the formula (V) with Boc anhydride in presence of triethylamine (TEA) and solvent to get compound of the formula (VI);

b) reducing compound of the formula (VI), followed by purification with acid-base treatment to get compound of the formula (VII); and

c) reacting compound of the formula (VII) with methanesulfonyl chloride in presence of organic base, followed by isolation or purification with suitable solvent to get 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I).

In an aspect of the present invention provides purification process of tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII) having purity greater than about 98.90%by HPLC, which comprises treatment of crude tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII) with an acid followed by a base.

In another aspect of the present invention provides purification process of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), which comprises:
a) dissolving a compound of Formula-I in an organic solvent;
b) heating the reaction mixture at 50-70ºC;
c) slowly cooling the reaction mixture to 25-30 ºC;
d) optionally adding anti-solvent to the mixture; and
e) isolating pure compound of Formula-I.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an improved process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate, which is used key intermediate for the preparation of Cariprazine Hydrochloride.

In one embodiment of the present invention provides a process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), comprising the steps of:
a) reacting compound of the formula (V) with Boc anhydride in presence of triethylamine (TEA) and solvent to get compound of the formula (VI);

b) reducing compound of the formula (VI), followed by purification with acid-base treatment to get compound of the formula (VII); and

c) reacting compound of the formula (VII) with methanesulfonyl chloride in presence of organic base, followed by isolation or purification with suitable solvent to get 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I).

According to embodiment of the present invention provides, which comprises Ethyl 2-((1R,4R)-4-aminocyclohexyl) acetate hydrochloride (V) is reacted with BOC anhydride in presence of triethylamine (TEA) / purified water to get Ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate (VI), which is undergoes reduction in presence of reducing agent, followed by purification with acid-base treatment at 20-50ºC to get pure tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII), further compound of formula (VII) is reacted with methanesulfonyl chloride in presence of organic base, followed by isolation or purification with suitable solvent to get 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I).

According to an embodiment of the present invention, wherein the reducing agent is selected from sodium borohydride (NaBH4), Pd/c, Raney Ni, lithium aluminium hydride (LiAlH4), diisobutyl aluminium hydride (DIBAH), Zn powder and Pt / H2.

According to an embodiment of the present invention, wherein the suitable solvent is selected from acetone, acetonitrile, dimethylformamide, dimelthylsulfoxide, isopropanol, methanol, ethanol, propanol, butanol, n-propyl alcohol, isopropyl alcohol, t-butyl alcohol, pentane, hexane, cyclohexane, n-heptane, benzene, toluene, xylene, acetic acid, chloroform, diethyl ether, ethyl acetate, methyl acetate, butyl acetate, isopropyl acetate, methoxy ethyl acetate, methylene chloride, pyridine, acetonitrile, propionitrile, N,N-dimethylformamide, tetrahydrofuran, N,N-dimethylacetamide, dimethyl sulfoxide, diethyl sulfoxide, methyl isobutyl ketone, methyl tert-butyl ether, pentanone, ethylmethylketone, diethyl ketone, dichloromethane, diethyl ether, dioxane and water or mixtures thereof.

In an embodiment of the present invention provides purification process of tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII) having purity greater than about 98.90% by HPLC, which comprises treatment of crude tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII) with an acid followed by a base.

According to embodiment of the present invention purification process of tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII), which comprises treating crude tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (VII) with conc. HCl (adjust the mass pH to 4.5-5.5) and extracted the product into toluene and separate the two layers. Taken the toluene layer add purified water followed by adjust the mass pH to 8.5-10.0 with 10% sodium bicarbonate solution. Further, washed the toluene layer with purified water and dried the toluene layer with sodium sulfate to get pure tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate having purity greater than about 98.90% by HPLC.

According to an embodiment of the present invention, wherein the suitable acid comprises organic acid or inorganic acid. The organic acid is selected from formic acid, oxalic acid, acetic acid, 2,2-dichloroacetic acid, adipic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamido-benzoic acid, camphoric acid, camphor- 10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane- 1,2- disulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene- 1,5-disulfonic acid, naphthalene- 2- sulfonic acid, l-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, salicyclic acid, 4-aminosalicyclic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, toluenesulfonic acid, and undecylenic acid. The inorganic acid is selected from hydrochloric acid, sulfuric acid, phosphoric acid or mixtures thereof.

According to an embodiment of the present invention, wherein the suitable base comprises inorganic base or organic base. The inorganic base is selected from alkaline metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; alkaline metal bicarbonates such as sodium bicarbonate and potassium bicarbonate. The organic base is selected from secondary and tertiary organic amines such as triethylamine (TEA), N, N-diethylisopropylamine, ?, ?-diisopropylethylamine (DIPEA), diethylamine, tripropylamine and trioctylamine.

In another embodiment of the present invention provides purification process of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), which comprises:
a) dissolving a compound of Formula-I in an organic solvent,
b) heating the reaction mixture at 50-70ºC
c) slowly cooling the reaction mixture to 25-30 ºC; and
d) optionally adding anti-solvent to the mixture;
e) isolating pure compound of Formula-I.

According to embodiment of the present invention provides, which comprises the compound of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I) dissolved in a organic solvent at below 55ºC and raise the temperature at 50-70ºC stir for 10-20 mins. Cooled the reaction mass to 25-30ºC and stirred the mass for 30-60 min followed by optionally adding anti-solvent to the mixture to isolate pure compound of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I).

According to an embodiment of the present invention, wherein the organic solvent or anti-solvent is selected from 1,4-dioxane, diethyl ether, tetrahydrofuran (THF), methyl tert-butyl ether (MTBE), n-heptane, cyclohexane, toluene, xylene, benzene, pentane, hexane, acetic acid, chloroform, methylene chloride, ethyl acetate (EtOAc) and isopropyl alcohol (IPA).

The following examples illustrate the present invention, but should not be construed as limiting the scope of the invention.

EXAMPLES
Example 1: Preparation of ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate
Charged purified water (1000 ml), ethyl 2-((1R,4R)-4-aminocyclohexyl) acetate hydrochloride (100 g) and triethylamine (100 g) into flask. Slowly added Boc anhydride (125 gm) into mass at 25-30ºC and stirred the mass for 3 hours. After completion of the reaction, filtered the material and washed with purified water (200 ml). The resultant mass was charged in toluene (300 ml), stirred and distilled out the solvent at below 65ºC under vacuum to get title compound.
Purity: 99.42%

Example 2: Preparation of ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate
Charged dichloromethane (1000 ml), ethyl 2-((1R,4R)-4-aminocyclohexyl) acetate hydrochloride (100 g) and triethylamine (100 g) into flask followed by slowly added Boc anhydride (125 gm) into mass at 25-30ºC, stirred the mass for 3 hours. After completion of the reaction, charged purified water (200 ml) into mass and stirred the mass. Separated the two layers and distilled out to get the title compound.
Purity: 99.25%

Example 3: Preparation of ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate.
Charged toluene (1000 ml), ethyl 2-((1R,4R)-4-aminocyclohexyl) acetate hydrochloride (100 g) and triethylamine (100 g) into flask followed by added Boc anhydride (125 gm) into mass at 25-30ºC, stirred the mass for 3 hours. After completion of the reaction, charged purified water (200 ml) into mass and stirred the mass. Separated the two layers and distilled out the solvent under vacuum to get the title compound.
Purity: 99.42%

Example 4: Preparation of tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate
Charged tetrahydrofuran (500 ml) and ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate (100 gm) into flask at 25-35ºC, stirred the mass. Add sodium borohydride (100 gm) at 25-35ºC. Raised the mass temperature to 60-65ºC. Slowly added methanol (100 ml) at reflux condition, stirred the mass for 2-3 hours at reflux condition. After completion of the reaction, cooled the reaction mass temperature to 10-15ºC. Charged toluene (1200 ml) and purified water (1000 ml) into mass at below 15ºC. Adjusted the reaction mass pH to 4.5-5.5 with conc. HCl (225 ml) at below 25ºC, separated the two layers. The toluene layer into flask and charged purified water (200 ml) into flask followed by adjusted the mass pH to 8.5-10.0 with 50% sodium hydroxide solution, separated the two layers. Take the toluene layer into flask and charged purified water (100 ml) into flask, stirred the mass. Separated the two layers and dried to get the title compound.
Purity: 98.90%

Example 5: Preparation of pure tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate.
Charged tetrahydrofuran (500 ml) and ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate (100 gm) into flask at 25-35ºC, stirred the mass. Added sodium borohydride (100 gm) at 25-35ºC. Raised the mass temperature to 60-65ºC. Slowly added methanol (100 ml) at reflux condition, stirred the mass for 2-3 hours at reflux condition. After completion of the reaction, cooled the reaction mass temperature to 10-15ºC. Charged toluene (1200 ml) and purified water (1000 ml) into mass at below 15ºC. Adjusted the mass pH to 4.5-5.5 with conc. HCl (225 ml) at below 25ºC, separated the two layers. The toluene layer into flask and charged purified water (200 ml) into flask followed by adjusted the mass pH to 8.5-10.0 with 10% sodium bicarbonate solution, separate the two layers. Take the toluene layer into flask and charged purified water (100 ml) into flask, stirred the mass. Separated the two layers and dried to get the title compound.
Purity: 98.78%

Example 6: Preparation of pure tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate
Charged tetrahydrofuran (500 ml) and ethyl 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) acetate (100 gm) into flask at 25-35ºC, stirred the mass. Add sodium borohydride (100 gm) at 25-35ºC. Raised the mass temperature to 60-65ºC. Slowly added methanol (100 ml) into mass at reflux condition, stirred the mass for 2-3 hours at reflux condition. After completion of the reaction, cooled the reaction mass temperature to 10-15ºC. Charged toluene (1200 ml) and purified water (1000 ml) into mass at below 15ºC. Adjusted the mass pH to 4.5-5.5 with acetic acid (450 ml) at below 25ºC. Separated the layers. The toluene layer into flask and charged purified water (200 ml) into flask followed by adjusted the mass pH to 8.5-10.0 with 20% sodium carbonate solution. Separated the two layers. The toluene layer into flask and charged purified water (100 ml) into flask, stirred the mass. Separated the two layers and dried to get the title compound.
Purity: 98.68%

Example 7: Preparation of pure 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate
Charged tert-butyl ((1R,4R)-4-(2-hydroxyethyl) cyclohexyl) carbamate (Equal to 100 gm) and triethylamine (120 gm) into flask, stirred and cooled the mass to 0-5ºC. Slowly added methane sulphonyl chloride (100 gm) at 0-5ºC, stirred. After completion of the reaction, charged purified water (500 ml) at 0-10ºC. Raised the mass temperature to 30-35ºC. Separated the two layers. Charged toluene (100 ml), stirred the mass, separated the two layers and distil out the solvent at below 55ºC. Charged MTBE (250 ml) into flask at below 55ºC and stirred the mass at 50-55ºC. The obtained reaction mass was cooled to 25-30ºC and stirred. Further cooled the mass to 0-5ºC. Filtered the material and washed the material with MTBE (50 ml) at 0-5ºC and dried the material to get the 120 gm of title compound.
Yield: 90.90%
Purity: 99.0%

Example 8: Preparation of pure 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate
Charged 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate and n-heptane (700 ml) into flask at below 55ºC and stirred the mass at 50-55ºC. The obtained reaction mass was cooled to 25-30ºC and filtered, followed by washed with n-heptane (100 ml) at 25-30ºC and dried the material to get the 118.0 gm of title compound.
Yield: 89.39%
Purity: 98.2%
Example 9: Purification of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate
Charged 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate and cyclohexane (700 ml) into flask at below 55ºC and stirred the mass at 50-55ºC. The obtained reaction mass was cooled to 25-30ºC, followed by filtered the material and washed with cyclohexane (100 ml) and dried the material to get the 110.0 gm of pure title compound.
Yield: 87.88%
Purity: 97.6%
Example 10: Purification of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate
Charged 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate and isopropyl alcohol (400 ml) into flask at below 55ºC and, stirred the mass at 60-65ºC. The obtained reaction mass was cooled to 0-5ºC and stirred, followed by filtered the material and washed with isopropyl alcohol (25 ml) at 0-5ºC and dried the material to get the 100.0 gm of title compound.
Yield: 75.75%
Purity: 91.50%
Example 11: Purification of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate
Charged 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate and ethyl acetate (50 ml) into flask at below 55ºC, stirred the mass. The obtained reaction mass was cooled to 25-30ºC. Added MTBE (200ml) into flask and cooled the mass to 0-5ºC. The obtained reaction mass was filtered and washed the material with MTBE (25 ml) at 0-5ºC, dried to get the 110.0 gm of title compound.
Yield: 89.33%
Purity: 99.6%
,CLAIMS:WE CLAIM:

1. A process for the preparation of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), comprising the steps of:

a) reacting compound of the formula (V) with Boc anhydride in presence of triethyl amine (TEA) and solvent to get compound of the formula (VI);

b) reducing compound of the formula (VI), followed by purification with acid-base treatment to get compound of the formula (VII); and

c) reacting compound of the formula (VII) with methanesulfonyl chloride in presence of organic base, followed by isolation or purification with suitable solvent to get 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I).

2. A process for purification of compound of the formula (VII), which comprises treatment of crude of compound of the formula (VII) with an acid followed by a base.

3. A process for purification of 2-((1R,4R)-4-((tert-butoxycarbonyl) amino) cyclohexyl) ethyl methane sulfonate (I), which comprises:
a) dissolving a compound of Formula-I in an organic solvent;
b) heating the reaction mixture at 50-70ºC;
c) slowly cooling the reaction mixture to 25-30 ºC;
d) optionally adding anti-solvent to the mixture; and
e) isolating pure compound of Formula-I.

4. The process as claimed in claim 1, wherein the reducing agent is selected from sodium borohydride (NaBH4), Pd/C, Raney Ni, lithium aluminum hydride (LiAlH4), diisobutyl aluminium hydride (DIBAH), Zn powder and Pt / H2.

5. The process as claimed in claim 1, wherein the suitable solvent is selected from acetone, acetonitrile, dimethylformamide, dimelthylsulfoxide, isopropanol, methanol, ethanol, propanol, butanol, n-propyl alcohol, isopropyl alcohol, t-butyl alcohol, pentane, hexane, cyclohexane, n-heptane, benzene, toluene, xylene, acetic acid, chloroform, diethyl ether, ethyl acetate, methyl acetate, butyl acetate, isopropyl acetate, methoxy ethyl acetate, methylene chloride, pyridine, acetonitrile, propionitrile, N,N-dimethylformamide, tetrahydrofuran, N,N-dimethylacetamide, dimethyl sulfoxide, diethyl sulfoxide, methyl isobutyl ketone, methyl tert-butyl ether, pentanone, ethylmethylketone, diethyl ketone, dichloromethane, diethyl ether, dioxane and water or mixtures thereof.

6. The process as claimed in claim1 and 2, wherein the suitable base comprises inorganic base or organic base. The inorganic base is selected from alkaline metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide; alkaline metal bicarbonates such as sodium bicarbonate and potassium bicarbonate. The organic base is selected from secondary and tertiary organic amines such as triethylamine, N, N-diethylisopropylamine, ?, ?-diisopropylethylamine, diethylamine, tripropylamine and trioctylamine.

7. The process as claimed in claim 1 and 2, wherein the suitable acid comprises organic acid or inorganic acid. The organic acid is selected from formic acid, oxalic acid, acetic acid, 2,2-dichloroacetic acid, adipic acid, ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamido-benzoic acid, camphoric acid, camphor- 10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane- 1,2- disulfonic acid, ethanesulfonic acid, 2-hydroxy-ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, glutaric acid, 2-oxo-glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, naphthalene- 1,5-disulfonic acid, naphthalene- 2- sulfonic acid, l-hydroxy-2-naphthoic acid, nicotinic acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, salicyclic acid, 4-aminosalicyclic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, toluenesulfonic acid, and undecylenic acid. The inorganic acid is selected from hydrochloric acid, sulfuric acid, phosphoric acid or mixtures thereof.

8. The process as claimed in claim 3, wherein the organic solvent or anti-solvent is selected from 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, n-heptane, cyclohexane, toluene, xylene, benzene, pentane, hexane, acetic acid, chloroform, methylene chloride, ethyl acetate and isopropyl alcohol.

9. The process as claimed in claim 1 and 2, compound of the formula (VII) having purity greater than about 98.90% by HPLC.

Dated this twenty ninth (29th) day of June, 2022