FIELD OF THE INVENTION
The present invention relates to a process for the preparation of the dihydrochloride monohydrate salt of (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole ("referred to herein as 'Pramipexole' or the compound of formula I"). In particular, the present invention provides an improved process for the preparation of the compound of formula I from (S)-2,6-diamino-4,5,6,7-tetrahydrobenzthiazole (referred to herein as the compound of formula II) and further conversion of the compound of formula I into its dihydrochloride monohydrate salt.
BACKGROUND OF THE INVENTION
Pramipexole, (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole, represented by the following formula I (the compound of formula I), is a dopamine D2/D3 agonist used for treatment of Schizophrenia, and particularly for the treatment of Parkinson's disease. Pramipexole is marketed in the form of dihydrochloride monohydrate salt, under the brand name Mirapex.

The compound of formula I is disclosed in US Patent no. 4,886,812 (US'812 Patent). The US' 812 Patent also describes a process for the preparation of the compound of formula I and its dihydrochloride monohydrate salt involving the propylation reaction of the compound of formula II with n-propylbromide as a propylating agent in the presence of potassium carbonate by using methanol as a solvent to provide the reaction mixture. The resulting reaction mixture is then refluxed for 3 hours. After completion of the reaction, water is added to the reaction mixture. The reaction mixture is then extracted with ethyl acetate and concentrated to obtain the residue. The obtained residue is purified by silica gel chromatography and the corresponding fraction is concentrated under reduced

pressure to obtain the compound of formula I which is then converted into its dihydrochloride monohydrate salt. Although, US'812 Patent describes the process for the preparation of the compound of formula I from the compound of formula II, it does not teach the process for converting the compound of formula I into its dihydrochloride monohydrate salt. Also, the process described in US'812 Patent involves propylation of the compound of formula II using 4 molar equivalents of n-propylbromide as the propylating agent. N-propylbromide is known to be carcinogenic compound and its average threshold limit value for 8 hours exposure is 10 parts per million. Therefore, on commercial scale, excess use of such a hazardous reagent is not desirable. Further, propylation of the compound of formula II using the process described in US'812 Patent generates one major impurity namely (6S)-2,6-benzothiazolediamine4,5,6,7-tetrahydro-N2,N6-dipropyl. The US'812 Patent does not teach any purification method for removal of this impurity.
Indian Patent Application no. 694/MUM/2006 describes a process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I involving treating the alcoholic solution of the compound of formula I with hydrochloric acid and precipitating the dihydrochloride monohydrate salt of the compound of formula I by addition of water. The process disclosed in this patent application does not involve any purification step for the purification of the compound of formula I or its dihydrochloride monohydrate salt and thus, the final active pharmaceutical ingredient (API), the dihydrochloride monohydrate salt of the compound of formula I prepared by this process does not have the desired pharmaceutically acceptable purity.
Indian patent application no. 605/MUM/2008 describes a process for the preparation of the dihydrochloride salt of the compound of formula I. The process for the preparation of the dihydrochloride salt of the compound of formula I involves the propylation reaction of the compound of formula II with n-propanal as a propylating agent by using a mixture of methanol and water as the solvent. To the resulting reaction mixture, glacial acetic acid and sodium

borohydride are charged and the reaction mixture is stirred for 30-40 minutes at a temperature of 15 to 20°C. The reaction mixture is then cooled to -5 to 0°C and to the reaction mixture; second lot of n-propanal with methanol and sodium borohydride is added. The resulting reaction mixture is stirred for 30-40 minutes and quenched with brine solution. The reaction mixture is distilled under vacuum to obtain a residue. To the obtained residue, ethyl acetate and water are added. Two layers formed are separated and ethyl acetate layer is concentrated under vacuum to obtain the crude compound of formula I. The resulting crude compound of formula I is then recrystallised by using acetonitrile to yield the pure compound of formula I. To the pure compound of formula I; ethanolic hydrochloric acid solution is added. The reaction mixture is stirred for 1 hour to precipitate the solid. The precipitated solid is filtered and suspended in ethanol. The reaction mixture is then stirred at reflux temperature for 30 minutes and at room temperature for 1 hour to precipitate the dihydrochloride salt of the compound of formula I. The precipitated dihydrochloride salt of the compound of formula I is dissolved in a mixture of ethanol and water; and filtered through hyflo. The filtrate is then distilled under vacuum and recrystallised by using ethanol to obtain the pure dihydrochloride salt of the compound of formula I. The process disclosed in said patent involves the use of 3 molar equivalents of sodium borohydride and n-propanal which renders the process costlier and hence, this process is not viable for scale up.
The general process for producing the dihydrochloride monohydrate salt of the compound of formula I is depicted in the following Scheme I:


In summary, the processes for the preparation of the compound of formula I as disclosed in the afore discussed patent documents involve the alkylation reaction of the compound of formula II with the 3-4 molar equivalents of propylating agent in the presence of an organic solvent to obtain (S)-2-amino-6-propinamido-4,5,6,7-tetrahydrobenzothiazole. The obtained (S)-2-amino-6-propinamido-4,5,6,7-tetrahydrobenzothiazole is reduced insitu by addition of 3-4 molar equivalents of sodium borohydride to obtain the compound of formula I,which is further converted into its dihydrochloride monohydrate salt. Thus, the process for the preparation of the compound of formula I involves the reductive alkylation of the compound of formula II. During reductive alkylation of the compound of formula II, one major impurity viz (6S)-,2,6-benzothiazolediamine-4,5,6,7-tetrahydro-N2,N6-dipropyl of formula III (hereinafter referred to as 'impurity B') is generated.


Also, the addition of sodium borohydride into the reaction mass generates high exotherm. Due to this high exotherm, another impurity viz (6S)-N6-(l-(((R)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)amino)-2-methylpentan-3-yl)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine of formula IV (hereinafter referred to as 'impurity C) is formed.

Further, incomplete conversion of the compound of formula II to the compound of formula I provides the compound of formula I contaminated with the starting material i.e. the compound of formula II, which will be referred to as the 'impurity A' when reference to it is made as an impurity.
The Indian patent application no. 605/MUM/2008, which is discussed above, describes purification method of the compound of formula I by using acetonitrile as a solvent. The purification in acetonitrile removes impurities A, B and C to some extent but does not provide the product, the dihydrochloride monohydrate salt of the compound of formula I having pharmaceutical acceptable purity. Thus, the purification of the compound of formula I by using acetonitrile does not provide the product, the dihydrochloride monohydrate salt of the compound of formula I having pharmaceutical acceptable purity. Further, the process described in said patent application requires 3 molar equivalents of n-propanal and sodium borohydride based on the compound of formula II. N-propanal and sodium borohydride are expensive reagents and therefore, use of the same in an excess amount renders the whole process costly.
Considering several drawbacks associated with the processes for the preparation of pramipexole (the compound of Formula I) dihydrochloride monohydrate salt, there is a need to develop a process for the preparation of the dihydrochloride

monohydrate salt of the compound of formula I that would minimize the quantity in which n-propanal and sodium borohydride are used in the reaction and also minimize the percentage of individual impurity A, B and C below 0.15% and provide the product, the dihydrochloride monohydrate salt of the compound of formula I in good yield and having pharmaceutical acceptable purity.
OBJECTS OF THE INVENTION
An object of the present invention is to provide an improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I comprising reacting the compound of formula II with n-propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as a solvent.
Another object of the present invention is to provide an improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I using minimum molar equivalents of n-propanal and sodium borohydride.
Another object of the present invention is to provide an improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I comprising the preparation of the compound of formula I by the reaction of the compound of formula II with n-propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as the solvent and conversion of the resulting compound of formula I to its monohydrochloride salt followed by recrystallisation of the monohydrochloride salt of the compound of formula I and finally, its conversion to the dihydrochloride monohydrate salt of the compound of formula I.
Yet another object of the present invention is to provide an improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I containing individual impurity A, B and C less than 0.15%.

Further object of the present invention is to provide an improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I having purity of 99.9%.
SUMMARY OF THE INVENTION
In accordance with an aspect of the present invention, there is to provided an improved process for producing the dihydrochloride monohydrate salt of the compound of formula I comprising the steps of,
A. reacting the compound of formula II with n-propanal and sodium
borohydride using a mixture of methanol and dichloromethane
(DCM) as the solvent to obtain the compound of formula I;
B. converting the compound of formula I as obtained in the step (A)
into its monohydrochloride salt by using 1 molar equivalent of
concentrated hydrochloric acid in an organic solvent or a mixture
thereof;
C. recrystallising the monohydrochloride salt of the compound of
formula I as obtained in the step (B) in a mixture of methanol
and water to obtain the pure monohydrochloride salt of the
compound of formula I;
D. converting the pure monohydrochloride salt of the compound of
formula I as obtained in the step (C) into its dihydrochloride
monohydrate salt by using 1 molar equivalent of concentrated
hydrochloric acid.
The process of the present invention for producing the dihydrochloride monohydrate salt of the compound of formula I is depicted in the following Scheme-II.


Importantly, the process for the preparation of the compound of formula I comprising the reaction of the compound of formula II with n-propanal and sodium borohydride using the mixture of methanol and DCM as a solvent to obtain the compound of formula I requires less molar equivalents of sodium borohydride and n-propanal. Also, the further conversion of the compound of formula I to its monohydrochloride salt followed by recrystallisation of the resulting monohydrochloride salt of the compound of formula I and further conversion of the pure monohydrochloride salt to the dihydrochloride monohydrate salt of the compound of formula I results in removing the individual impurity A, B and C less than 0.15% which ultimately results the product, the dihydrochloride monohydrate salt of the compound of formula I with higher purity.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention relates to an improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I.
According to the present invention, the improved process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I involves reaction of the compound of formula II with n-propanal and sodium borohydride using the mixture of methanol and DCM as a solvent to obtain the compound of formula I and further conversion of the compound of formula I to

its monohydrochloride salt followed by recrystallisation of the resulting monohydrochloride salt of the compound of formula I and further conversion of the pure monohydrochloride salt to the dihydrochloride monohydrate salt of the compound of formula I.

comprises the steps of,
A. reacting the compound of formula II;

According to the present invention, a process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I,
with n-propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as the solvent to obtain the compound of formula I;
B. converting the compound of formula I as obtained in the step (A)
into its monohydrochloride salt by using 1 molar equivalent of
concentrated hydrochloric acid in an organic solvent or a mixture
thereof;
C. recrystallising the monohydrochloride salt of the compound of
formula I as obtained in the step (B) in a mixture of methanol
and water to obtain the pure monohydrochloride salt of the
compound of formula I: and
D. converting the pure monohydrochloride salt of the compound of
formula I as obtained in the step (C) into its dihydrochloride

monohydrate salt by using 1 molar equivalent of concentrated hydrochloric acid in isopropyl alcohol.
In the context of the present invention the compound of formula I is obtained by reacting the compound of formula II with propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as the solvent. The compound of formula I as obtained in the step (A) is further converted into its monohydrochloride salt in the step (B). In step (C), the monohydrochloride salt as obtained in step (B) purified with the mixture of methanol-water and further converted into dihydrochloride monohydrate salt in the step (D).
In an embodiment of the present invention, in the step (A) of the process, n-propanal is used in an amount ranging from 1 to 2 molar equivalents based on the compound of formula II.
In an embodiment of the present invention, in the step (A) of the process, sodium borohydride is used in an amount ranging from 0.4 to 1 molar equivalent based on the compound of formula II.
In an embodiment of the present invention, in the step (A) of the process, methanol is used in an amount ranging from 15 to 20 volumes based on the compound of formula II.
In an embodiment of the present invention, in the step (A) of the process, DCM is used in an amount ranging from 15 to 20 volumes based on the compound of formula II.
In an embodiment of the present invention, in the step (A) of the process, the ratio of methanol to DCM used is 1:1.
In an embodiment of the present invention, the organic solvent used in the step (B) of the process, is selected from the group consisting of methanol, isopropyl alcohol, toluene, methyl tert-butyl ether (MTBE). n-hexane and ethyl acetate or a mixture thereof.

In an embodiment of the present invention, in the step (B) of the process, the organic solvent or the mixture of organic solvents is used in an amount ranging from 1 to 10 volumes based on the compound of formula II.
In an embodiment of the present invention, in the step (C) of the process, methanol is used in an amount ranging from 2 to 15 volumes based on the compound of formula II.
In an embodiment of the present invention, in the step (C) of the process, water is used in an amount ranging from 0.03 to 0.07% based on the compound of formula II.
In an embodiment of the present invention, in the step (D) of the process, isopropyl alcohol is used in an amount ranging from 2 to 15 volumes based on the compound of formula II.
The starting material of the process, i.e. the compound of formula II is a known compound and can be prepared by a person skilled in the art by following methods described in the art, for example, by the process described in WO2008104847. The process involves reaction of N-(4-oxocyclohexyl) acetamide with thiourea in the presence of bromine and acetic acid to obtain a reaction mixture. To the reaction mixture, dilute sulphuric acid was added to obtain sulphate salt of the compound of formula II. To the sulphate salt of the compound of the formula II, sodium hydroxide was added to obtain the racemic compound of formula II. The racemic compound of formula II was further resolved using tartaric acid to obtain the S isomer of the compound of formula II.
According to the present invention, the process for the preparation of the dihydrochloride monohydrate salt of the compound of formula I involves reaction of the compound of formula II with n-propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as the solvent at a temperature of 25-30°C. After completion of the reaction, the reaction mixture was quenched with brine solution. The quenched reaction

mixture was further concentrated up to 15-16 volumes under vacuum at a temperature of 50-55°C. The reaction mixture was cooled to a temperature of 15-20°C. To the reaction mixture, potassium carbonate, ethyl acetate and methanol were charged. The two layers formed were separated. The organic layer was then concentrated up to 7 to 8 volumes. To the organic layer, ethyl acetate and brine solution were added. The two layers formed were separated. The organic layer was treated with activated charcoal and filtered through hyflo. The organic layer was then concentrated under vacuum to obtain a residue. To the obtained residue, diisopropyl ether was added and the reaction mass was stirred for 20-30 minutes at a temperature of 45-50°C The reaction mixture was then cooled to a temperature of 25-30°C to obtain solid. The obtained solid was then filtered, washed with diisopropyl ether to obtain the compound of formula I. The obtained compound of formula I was further converted into its monohydrochloride salt. The conversion of the compound of formula I into its monohydochoride salt involves the addition of 1 mole equivalent of concentrated hydrochloric acid to the solution of the compound of formula I in isopropyl alcohol (1PA) at a temperature of 15-20°C to obtain monohydrochloride salt of the compound of formula I. The obtained monohydrochloride salt of the compound of formula I was then filtered and washed with isopropyl alcohol. The monohydrochloride salt of the compound of formula I was then purified using a mixture of methanol and water. The purification of the monohydrochloride salt of the compound of the formula I involves the charging of the monohydrochloride salt of the compound of formula I and the mixture of methanol-water to the reaction flask and the reaction mixture was heated to the reflux temperature. The reaction mixture was then cooled to a temperature of 25-30°C to precipitate solid. The precipitated solid was then filtered and washed with isopropyl alcohol (IPA) to obtain the pure monohydrochloride salt of the compound of formula I which was further converted into the dihydrochloride monohydrate salt of the compound of formula I. The process for the conversion of the pure monohydrochloride salt of

the compound of formula I into the corresponding dihydrochloride monohydrate salt involves the charging of the pure monohydrochloride salt of the compound of formula I and isopropyl alcohol to the reaction flask at 25-30°C. To the reaction mass 1 mole equivalent of concentrate dihydrochloric acid was added at a temperature of 10-15°C to precipitate solid. The precipitated solid was then filtered and dried under vacuum to obtain the dihydrochloride monohydrate salt of the compound of formula I.
The inventors of the present invention have observed that the dihydrochloride monohydrate salt of the compound of formula I prepared from the compound of formula II through an improved process involving the reductive amination of the compound of formula II with n-propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as a solvent to obtain the compound of formula I, conversion of the compound of formula I into its monohydrate salt followed by the recrystallization of the monohydrochloride salt of the compound of formula I with a mixture of methanol-water to obtain the pure monohydrochloride salt of the compound of formula I and conversion of the pure monohydrochloride salt of the compound of formula I into the dihydrochloride monohydrate salt of the compound of formula I having individual impurity A, B and C below 0.15% and having pharmaceutical acceptable purity.
The following examples which fully illustrate the practice of the preferred embodiments of the present invention are intended for illustrative purpose only and should not be construed in any way to limit the scope of the present invention.
Examples
Example 1:
Step A: Synthesis of compound of formula I:
To the reaction flask dichloromethane (1500ml), methanol (1500ml) and the compound of formula II (lOOgm) were charged at a temperature of 25-3 0°C.

The reaction mixture was cooled to a temperature of 3-8°C and to the reaction mixture, sulphuric acid (8.69 gm); n-propanal (13.98ml) and sodium borohydride (2.46g) were charged. The reaction mixture was stirred for 20-30 minutes at a temperature of 3-8°C. To the reaction mixture, n-propanal (41.94g) followed by sodium borohydride (7.38g) were added in three different lots at a temperature of 3-8°C. After completion of the reaction, the reaction mixture was quenched with brine solution. The quenched reaction mixture was further concentrated up to 15-16 volumes at 50-55°C under vacuum. The reaction mixture was cooled to 15-20°C. To the reaction mixture potassium carbonate (150g), ethyl acetate (900ml) and methanol (100ml) were charged. The two layers formed were separated. The organic layer was then concentrated up to 7 to 8 volumes. To the organic layer ethyl acetate (500ml) and brine solution (240g) were added. The two layers formed were separated. The organic layer was treated with activated charcoal and filtered through hyflo. The organic layer was then concentrated under vacuum to obtain residue. To the obtained residue diisopropyl ether (200ml) was added and reaction mixture was stirred for 20-30 minutes at 45-50°C. The reaction mixture was then cooled at 25-30°C to precipitate solid. The precipitated solid was then filtered and washed with diisopropyl ether (200ml) to obtain the compound of formula I.
Step B: Synthesis of monohydrochloride salt of the compound of formula I:
To the reaction flask, the compound of formula I (as obtained in the step A) and isopropyl alcohol (900ml) were charged and the reaction mixture was stirred at a temperature of 25-35°C for 1 hour. The reaction mixture was then filtered through hyflo and washed with isopropyl alcohol (100ml). To the filtrate cone. hydrochloric acid (42.20ml) was added to obtain a solid. The obtained solid was then filtered and washed with isopropyl alcohol (200ml) to yield the monohydrochloride salt of the compound of formula I.
Step C: Purification of the monohydrochloride salt of the compound of formula I:

To the reaction flask, the monohydrochloride salt of the compound of formula I (as obtained in the step B) and the mixture of methanol (300ml) and water (5.01ml) were charged and the reaction mixture was stirred at a temperature of 55-60°C for 2 hours. The resulting reaction mixture was then cooled to a temperature of 20-25°C to precipitate solid. The precipitated solid was then filtered and washed with isopropyl alcohol (200ml) to obtain the pure monohydrochloride salt of the compound of formula I.
Step D: Synthesis of the dihydrochloride monohydrate salt of the compound of formula I:
To the reaction flask, the pure monohydrochloride salt of the compound of formula I (as obtained in the step C), methanol (600ml) and cone, hydrochloric acid (33.67ml) were charged and the reaction mass was stirred at a temperature of 3-8°C for 2 hours. To the reaction mass, activated charcoal (4g) was charged and the reaction mass was stirred for 30-45 minutes at temperature of 40-50°C. The activated charcoal was filtered through hyflo and filtrate was concentrated under vacuum to obtain residue. To the residue, isopropyl alcohol (700ml) was charged and the reaction mass was maintained for 2-3 hours at 15-20°C to precipitate solid. The precipitated solid was then filtered and washed with isopropyl alcohol (100ml). The solid was then dried under vacuum to yield dihydrochloride monohydrate salt of the compound of formula 1. Yield 36%, purity 99.77%.
Details for 11 PLC analysis:
Column: Inertsil ODS-3, 125 X 4.0 mm, 5um
Part No: C/N 5020
Mobile phase
Mobile phase A: Buffer solution
Mobile phase B: Acetonitrile: Buffer (500:500 v/v)
Flow rate: 1.5 ml/min

Injection volume: 5 μl
Run time: 25 minutes
Detector: 264 nm.
Column temperature: 40°C
Diluent: Acetonitrile: Buffer (200:800 v/v)
Procedure:
For system suitability inject (5μL) of the system suitability solution. The resolution between Pramipexole (the compound of formula [) related compound and Pramipexole should not be less than 6.0. The tailing factor for Pramipexole should not be more than 2.0. Inject Standard solution in six replicates into the chromatograph. For the Pramipexole peak, the relative standard deviation should not be more than 5.0%.
Inject (5fiL) of blank preparation and test solution into the chromatograph, measure the responses of all the peaks and calculate all known impurities and unknown impurities by the formula given below. In the sample chromatogram disregard any peak due to the blank. Retention time and relative retention times are given in the table below.
Calculation:-

Where:
SPL (Area) - is area of peak due to impurities in sample preparation.
STD (Area) - is mean area of peak of Pramipexole in reference solution (a) for
six injections.
Conc SPL - concentration of Pramipexole in test solution in mg/mL
Conc STD - concentration of Pramipexole in test solution in mg/mL

WE CLAIM,
1. A process for the preparation of the dihydrochloride monohydrate salt of a compound of formula I,

comprising the steps of,
A. reacting the compound of formula II;

with n-propanal and sodium borohydride using a mixture of methanol and dichloromethane (DCM) as a solvent to obtain the compound of formula I;
B. converting the compound of formula I as obtained in the step (A)
into its monohydrochloride salt by using 1 molar equivalent of
concentrated hydrochloric acid in an organic solvent or a mixture
thereof;
C. recrystallising the monohydrochloride salt of the compound of
formula I as obtained in the step (B) in a mixture of methanol
and water to obtain the pure monohydrochloride salt of the
compound of formula I; and
D. converting the pure monohydrochloride salt of the compound of
formula I as obtained in the step (C) into its dihydrochloride
monohydrate salt by using 1 molar equivalent of concentrated
hydrochloric acid in isopropyl alcohol.

2. The process as claimed in claim 1, wherein in the step (A), n-propanal is used in an amount ranging from 1 to 2 molar equivalents based on the compound of formula II.
3. The process as claimed in claim 1, wherein in the step (A), sodium borohydride is used in an amount ranging from 0.4 to 1 molar equivalent based on the compound of formula II.
4. The process as claimed in claim 1, wherein in the step (A), methanol is used in an amount ranging from 15 to 20 volumes based on the compound of formula II.
5. The process as claimed in claim 1, wherein in the step (A), DCM is used in an amount ranging from 15 to 20 volumes based on the compound of formula II.
6. The process as claimed in claim 1, wherein in the step (A), methanol-DCM is used in a ratio of 1:1.
7. The process as claimed in claim 1, wherein the organic solvent used in the step (B) is selected from the group consisting of methanol, isopropyl alcohol, toluene, methyl tert-butyl ether (MTBE), n-hexane and ethyl acetate or a mixture thereof.
8. The process as claimed in claim 1 or claim 7, wherein in the step (B), the organic solvent or the mixture of organic solvent is used in an amount ranging from 1 to 10 volumes based on the compound of formula II.
9. The process as claimed in claim 1, wherein in the step (C), methanol is used in an amount ranging from 2 to 15 volumes based on the compound of formula II.

10. The process as claimed in claim 1, wherein in the step (C), water is used in an amount ranging from 0.03 to 0.07% based on the compound of formula II.
11. The process as claimed in claim 1, wherein in the step (D), isopropyl alcohol is used in an amount ranging from 2 to 15 volumes based on the compound of formula II.