WO2007054970A2 - Novel polymorphic forms of (s)-(-)-2-amino-6-(n- propylamino) 4,5,6,7- tetrahydrobenzothiazole - Google Patents

Novel polymorphic forms of (s)-(-)-2-amino-6-(n- propylamino) 4,5,6,7- tetrahydrobenzothiazole Download PDF

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WO2007054970A2
WO2007054970A2 PCT/IN2006/000377 IN2006000377W WO2007054970A2 WO 2007054970 A2 WO2007054970 A2 WO 2007054970A2 IN 2006000377 W IN2006000377 W IN 2006000377W WO 2007054970 A2 WO2007054970 A2 WO 2007054970A2
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amino
propylamino
tetrahydrobenzothiazole
formula
preparation
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PCT/IN2006/000377
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French (fr)
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WO2007054970A3 (en
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Pandurang Balwant Deshpande
Anand Kumar Pandey
Sanjay Lakhabha Vasoya
Piyush Mansukhbhai Vaghasia
Kamlesh Sanmukhbhai Soni
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Alembic Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D277/82—Nitrogen atoms

Definitions

  • the present invention relates to novel polymorphic forms of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) and process of their preparation. More particularly the present invention discloses four novel polymorphic forms of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I) designated as Form I 1 II, III and IV.
  • the compound of formula (I) is commonly known as Pramipexole.
  • Pramipexole belongs to a group of 2-amino-6-(substituted)amino-4,5,6,7- tetrahydro benzothiazoles having general formula (A), wherein Ri is hydrogen, alkyl or aralkyl group and R 2 is hydrogen.
  • A 2-amino-6-(substituted)amino-4,5,6,7- tetrahydro benzothiazoles having general formula (A), wherein Ri is hydrogen, alkyl or aralkyl group and R 2 is hydrogen.
  • Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes in solid state. Thus, polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties. Therefore a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as solubility profiles, melting point temperatures and/or x-ray diffraction pattern. Polymorphs of a compound can be characterized by x-ray diffraction pattern, Infrared Spectrum, DSC etc.
  • Another object of the invention is to provide novel polymorphic forms of (S)-(-)-2- Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form I, II, III and IV.
  • Yet another object of the invention is to provide processes for preparation of novel polymorphic forms of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I) designated as Form I, II, III and IV.
  • Formula (I) characterized by PXRD peaks at 9.7, 13.0, 16.6, 18.7, 21.9 ⁇ 0.2°-2 ⁇ .
  • the present invention provides the process for the preparation of Form I of (S)-(-) ⁇ 2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I).
  • Formula (I) characterized by PXRD peaks at 7.9, 15.8, 19.7, 23.7, 24.4 ⁇ 0.2°-2 ⁇ .
  • the present invention provides the process for the preparation of Form Il of (S)-(-)-2-Amino-6-(n-propylamino)-4, 5,6,7- tetrahydrobenzothiazole of formula (I).
  • Formula (I) characterized by PXRD peaks at 12.0, 21.4, 24.2, 24.7, 25.0 ⁇ 0.2°-2 ⁇ .
  • the present invention provides the process for the preparation of Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I).
  • a novel polymorph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form IV,
  • Formula (I) characterized by PXRD peaks at 15.6, 18.5, 19.9, 20.8, 25.8 ⁇ 0.2°-2 ⁇ .
  • the present invention also provides the process for the preparation of Form IV of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I).
  • (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole used herein in specification and claims is intended to include Pramipexole and its pharmaceutically acceptable salts, and hydrates or solvates thereof in any state of purity unless specifically mentioned.
  • novel polymorphic form of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form I is characterized by PXRD peaks at 9.7, 13.0, 16.6, 18.7, 21.9 ⁇ 0.2°-2 ⁇ . It is further characterized by PXRD peaks at 10.8, 17.3, 17.7, 21.5, 22.4 ⁇ 0.2°-2 ⁇ .
  • the process for the preparation of Form I of (S)-(-)-2-Amino-6-(n-propylamino)- 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino- 6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with solvent selected from acetonitrile, acetone, water and mixtures there of to obtain Form I of (S)-(-)-2- Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
  • Form I can be prepared by treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with solvent selected from ethyl acetate, dichloro methane, methyl isobutyl ketone and the like to obtain solution and adding anti-solvent selected from hexane, diisoproyl ether, diethyl ether, methyl tert-buty ⁇ ether, cyclohexane to the said solution to obtain Form I of (S)-(- )-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
  • solvent selected from ethyl acetate, dichloro methane, methyl isobutyl ketone and the like
  • anti-solvent selected from hexane, diisoproyl ether, diethyl ether, methyl tert-buty ⁇
  • Another process for the preparation of Form I of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole comprises treating the solution of acid addition salt of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole, preferably hydrochloride or dihydrochloride salts with base selected from alkali and alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, cesium hydroxide and the like to obtain Form I of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole.
  • base selected from alkali and alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, cesium hydroxide and the like
  • the solution of acid addition salt of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole is meant to include any solvent, in which acid addition salt of (S)-(-)-2-Amino-6-(n ⁇ propylamino)-4,5,6,7-tetrahydrobenzothiazole is soluble.
  • Preferred solvent is selected from water, alcohols such as methanol, ethanol, isopropanol, n- propanol, tert-butanol and mixtures thereof.
  • Form I obtained by above procedures can be isolated by conventional methods and dried.
  • Form Il another novel polymorphic form of (S)- (-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form Il is characterized by PXRD peaks at 7.9, 15.8, 19.7, 23.7, 24.4 ⁇ 0.2°-2 ⁇ . It is further characterized by PXRD peaks at 17.9, 18.4, 20.5, 26.0, 27.5 ⁇ 0.2°-2 ⁇ .
  • the process for the preparation of Form Il of (S)-(-)-2-Amino-6-(n-propylamino)- 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino-
  • Form Il is prepared by treating methanolic solution of (S)-(-)-2-Amino- 6-(n-propylamino)-4,5 . ,6,7-tetrahydrobenzothiazole with 1.1 molar equivalent of cone, hydrochloric acid at about 40 to 50 0 C temperature and subsequently cooling it to obtain Form Il of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole.
  • Form Il obtained by above procedure can be isolated by conventional methods and dried.
  • Yet another aspect of the present invention provides novel polymorphic form of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form III, characterized by PXRD peaks at 12.0, 21.4, 24.2, 24.7, 25.0 ⁇ 0.2°-2 ⁇ . It is further characterized by PXRD peaks at 13.0, 13.3, 13.9, 19.5, 25.6, 28.5 ⁇ 0.2°-2 ⁇ .
  • the process for the preparation of Form III of (S)-(-)-2-Amino-6-(n-propylamino) ⁇ 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino- 6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with 1.8 to 2.2 M equivalent hydrochloric acid in alcohol selected from methanol, ethanol, isopropanol, n- propanol, tert-butanol and mixtures thereof to obtain Form III of (S)-(-)-2-Amino-6- (n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
  • Form III is prepared by treating solution of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole in ethanol-water with 20% ethanolic hydrochloric acid solution at 40 to 60 0 C temperature and subsequently cooling it to obtain Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole.
  • Form III obtained by above procedure can be isolated by conventional methods and dried.
  • yet another novel polymorphic form of (S)-(-)- 2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazoIe of formula (I) designated as Form IV is characterized by PXRD peaks at 15.6, 18.5, 19.9, 20.8, 25.8 + 0.2°-2 ⁇ .. It is further characterized by PXRD peaks at 12.9, 13.7, 24.2, 24.9, 26.6 ⁇ 0.2°-2 ⁇ .
  • the process for the preparation of Form IV of (S)-(-)-2-Amino-6-(n-propylamino)- 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino- 6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazoIe with anhydrous alcohol selected from methanol, ethanol, isopropanol, n-propanol, tert-butanol and mixtures thereof to obtain solution , optionally cooling the said solution and passing HCI gas to obtain Form IV.
  • the said HCI gas is preferably dry.
  • Alternate process for the preparation of Form IV of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with alcohol selected from methanol, ethanol, isopropanol, n-propanol, tert- butanol and mixtures thereof to obtain solution and concentrating the solution to obtain Form IV.
  • Form IV obtained by above procedures can be isolated by conventional methods and dried.
  • Example 3 Preparation of Form III (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (10g) was added to ethanol (90ml) and the reaction mixture is heated to 55-60 0 C to get a clear solution. The reaction mixture is charcoalized and filtered. Water (90ml) was added to the filtrate and cooled to 0-5°C. -20% Ethanolic HCI (180 ml) was added drop wise to the reaction mixture till pH 2. The temperature of the reaction mixture was raised to 25-35°C and stirred for 12-15 hours. The product was filtered and dried at 25-35 0 C to obtain Form III of (S)-(-)-2-Amino-6-(n- prqpylamino)-4,5,6,7-tetrahydrobenzothiazole.
  • Example 4 Preparation of Form IV (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (20 g) is dissolved in methanol (500ml) and hydrochloric acid gas is purged at 0-5°C. The reaction mixture is then stirred and filtered, washed with methanol, dried at 4O 0 C to get (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form IV. The product is filtered, washed and dried at 40 0 C under vacuum (19.9g)
  • Example 5 Preparation of Form IV Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (2Q g) was suspended in ethanol (100 ml) and ethanol was recovered completely under reduced pressure at 40 0 C to get (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole Form IV. The product is filtered, washed and dried at 40 0 C under vacuum (19.9g).
  • Figure 1 represents PXRD graph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form I.
  • Figure 2 represents PXRD graph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form II.
  • Figure 3 represents PXRD graph of (S)-(-)-2-Amino ⁇ 6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form III.
  • Figure 4 represents PXRD graph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form IV.

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Abstract

The present invention relates to novel polymorphic forms of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole designated as Form I, II, III and IV and its process for preparation.

Description

NOVEL POLYMORPHIC FORMS OF (S)-f-)-2-AMINO-6-(N- PROPYLAMINO) 4,5,6,7- TETRAHYDROBENZOTHIAZOLE
Filed of invention:
The present invention relates to novel polymorphic forms of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) and process of their preparation. More particularly the present invention discloses four novel polymorphic forms of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I) designated as Form I1 II, III and IV. The compound of formula (I) is commonly known as Pramipexole.
Figure imgf000002_0001
Formula (I)
Background of the invention and prior art:
(S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole is known as Pramipexole and belongs to a group of 2-amino-6-(substituted)amino-4,5,6,7- tetrahydro benzothiazoles having general formula (A), wherein Ri is hydrogen, alkyl or aralkyl group and R2 is hydrogen. These compounds are first described in US Patent No. 4,843,086. They are useful for treatment of schizophrenia, Parkinson's disease or parkinsonism, and/or hypertension. The processes for the preparation of Pramipexole and its pharmaceutically acceptable salts are known in literature.
Figure imgf000002_0002
Formula (A)
Polymorphism is the occurrence of different crystalline forms of a single compound and it is a property of some compounds and complexes in solid state. Thus, polymorphs are distinct solids sharing the same molecular formula, yet each polymorph may have distinct physical properties. Therefore a single compound may give rise to a variety of polymorphic forms where each form has different and distinct physical properties, such as solubility profiles, melting point temperatures and/or x-ray diffraction pattern. Polymorphs of a compound can be characterized by x-ray diffraction pattern, Infrared Spectrum, DSC etc.
The polymorphic form of (S)-(-)-2-Amino-6~(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole are not reported in literature. The inventors of present invention have now found that (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole exhibits polymorphism. These polymorphic forms are characterized as Form I, II, III and IV.
Object of the invention:
It is the primary object of the present invention to provide novel polymorphic forms of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazoIe of formula (I).
Another object of the invention is to provide novel polymorphic forms of (S)-(-)-2- Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form I, II, III and IV.
Yet another object of the invention is to provide processes for preparation of novel polymorphic forms of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I) designated as Form I, II, III and IV.
Summary of the invention: According to one aspect of present invention, there is provided a novel polymorph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form I,
Figure imgf000003_0001
Formula (I) characterized by PXRD peaks at 9.7, 13.0, 16.6, 18.7, 21.9 ± 0.2°-2θ.
According to another aspect the present invention provides the process for the preparation of Form I of (S)-(-)~2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I).
According to another aspect of the invention, there is provided a novel polymorph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form II,
Figure imgf000004_0001
Formula (I) characterized by PXRD peaks at 7.9, 15.8, 19.7, 23.7, 24.4 ± 0.2°-2θ.
According to a further aspect the present invention provides the process for the preparation of Form Il of (S)-(-)-2-Amino-6-(n-propylamino)-4, 5,6,7- tetrahydrobenzothiazole of formula (I).
According to further aspect of the invention, there is provided a novel polymorph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form III,
Figure imgf000004_0002
Formula (I) characterized by PXRD peaks at 12.0, 21.4, 24.2, 24.7, 25.0 ± 0.2°-2θ. According to another aspect the present invention provides the process for the preparation of Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I). According to yet another "aspect of the invention, there is provided a novel polymorph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form IV,
Figure imgf000005_0001
Formula (I) characterized by PXRD peaks at 15.6, 18.5, 19.9, 20.8, 25.8 ± 0.2°-2θ.
According to further aspect the present invention also provides the process for the preparation of Form IV of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole of formula (I).
Detailed description of the invention:
The term "(S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole", used herein in specification and claims is intended to include Pramipexole and its pharmaceutically acceptable salts, and hydrates or solvates thereof in any state of purity unless specifically mentioned.
According the present invention, novel polymorphic form of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form I is characterized by PXRD peaks at 9.7, 13.0, 16.6, 18.7, 21.9 ± 0.2°-2θ. It is further characterized by PXRD peaks at 10.8, 17.3, 17.7, 21.5, 22.4 ± 0.2°-2θ.
The process for the preparation of Form I of (S)-(-)-2-Amino-6-(n-propylamino)- 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino- 6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with solvent selected from acetonitrile, acetone, water and mixtures there of to obtain Form I of (S)-(-)-2- Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
Alternatively, Form I can be prepared by treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with solvent selected from ethyl acetate, dichloro methane, methyl isobutyl ketone and the like to obtain solution and adding anti-solvent selected from hexane, diisoproyl ether, diethyl ether, methyl tert-buty\ ether, cyclohexane to the said solution to obtain Form I of (S)-(- )-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
Another process for the preparation of Form I of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole comprises treating the solution of acid addition salt of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole, preferably hydrochloride or dihydrochloride salts with base selected from alkali and alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, cesium hydroxide and the like to obtain Form I of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole. The solution of acid addition salt of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole is meant to include any solvent, in which acid addition salt of (S)-(-)-2-Amino-6-(n~ propylamino)-4,5,6,7-tetrahydrobenzothiazole is soluble. Preferred solvent is selected from water, alcohols such as methanol, ethanol, isopropanol, n- propanol, tert-butanol and mixtures thereof.
Form I obtained by above procedures can be isolated by conventional methods and dried.
In accordance with the present invention, another novel polymorphic form of (S)- (-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form Il is characterized by PXRD peaks at 7.9, 15.8, 19.7, 23.7, 24.4 ± 0.2°-2θ. It is further characterized by PXRD peaks at 17.9, 18.4, 20.5, 26.0, 27.5 ± 0.2°-2θ.
The process for the preparation of Form Il of (S)-(-)-2-Amino-6-(n-propylamino)- 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino-
6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with 0.8 to 1.2 M equivalent hydrochloric acid in alcohol selected from methanol, ethanol, isopropanol, n- propanol, tert-butanol and mixtures thereof to obtain Form Il of (S)-(-)-2-Amino-6- (n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
Preferably, Form Il is prepared by treating methanolic solution of (S)-(-)-2-Amino- 6-(n-propylamino)-4,5.,6,7-tetrahydrobenzothiazole with 1.1 molar equivalent of cone, hydrochloric acid at about 40 to 500C temperature and subsequently cooling it to obtain Form Il of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole.
Form Il obtained by above procedure can be isolated by conventional methods and dried.
Yet another aspect of the present invention provides novel polymorphic form of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) designated as Form III, characterized by PXRD peaks at 12.0, 21.4, 24.2, 24.7, 25.0 ± 0.2°-2θ. It is further characterized by PXRD peaks at 13.0, 13.3, 13.9, 19.5, 25.6, 28.5 ± 0.2°-2θ.
The process for the preparation of Form III of (S)-(-)-2-Amino-6-(n-propylamino)~ 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino- 6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with 1.8 to 2.2 M equivalent hydrochloric acid in alcohol selected from methanol, ethanol, isopropanol, n- propanol, tert-butanol and mixtures thereof to obtain Form III of (S)-(-)-2-Amino-6- (n-propylamino)-4,5,6,7-tetrahydrobenzothiazole.
Preferably, Form III is prepared by treating solution of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole in ethanol-water with 20% ethanolic hydrochloric acid solution at 40 to 600C temperature and subsequently cooling it to obtain Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole. Form III obtained by above procedure can be isolated by conventional methods and dried.
According to the present invention, yet another novel polymorphic form of (S)-(-)- 2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazoIe of formula (I) designated as Form IV is characterized by PXRD peaks at 15.6, 18.5, 19.9, 20.8, 25.8 + 0.2°-2θ.. It is further characterized by PXRD peaks at 12.9, 13.7, 24.2, 24.9, 26.6± 0.2°-2θ.
The process for the preparation of Form IV of (S)-(-)-2-Amino-6-(n-propylamino)- 4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating (S)-(-)-2-Amino- 6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazoIe with anhydrous alcohol selected from methanol, ethanol, isopropanol, n-propanol, tert-butanol and mixtures thereof to obtain solution , optionally cooling the said solution and passing HCI gas to obtain Form IV. The said HCI gas is preferably dry.
Alternate process for the preparation of Form IV of (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula (I) comprises treating Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with alcohol selected from methanol, ethanol, isopropanol, n-propanol, tert- butanol and mixtures thereof to obtain solution and concentrating the solution to obtain Form IV.
Form IV obtained by above procedures can be isolated by conventional methods and dried.
(S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole used in experimental procedures is prepared in accordance with process know perse or by any method of preparation known to person skilled in art.
The process of the present invention is described by the following examples, which are illustrative only and should not be construed so as to limit the scope of the invention in any manner. Examples:
Example 1: Preparation of Form I
(S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydr.obenzothiazole (5Og) was added to 125 ml of acetonitrile and heated to 80-860C. The reaction mixture was cooled to about 20-250C and product was filtered, washed and dried at 45-60°C to obtain 48 g of Form I of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole.
Example 2: Preparation of Form Il
A solution of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (8.4g) in Methanol (30ml) was heated the to 40°-42°C followed by addition of cone. HCI (3.3ml) slowly over a period of 20-30 min. at 40°-42°C. The reaction mixture was stirred for 30 min at 40°-42°C. Subsequently the reaction mixture was cooled to 25°-35°C. Material is filtered and air dried at 25°-35°C for 12-15 hours to obtain 6.34 g of Form Il of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole.
Example 3: Preparation of Form III (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (10g) was added to ethanol (90ml) and the reaction mixture is heated to 55-600C to get a clear solution. The reaction mixture is charcoalized and filtered. Water (90ml) was added to the filtrate and cooled to 0-5°C. -20% Ethanolic HCI (180 ml) was added drop wise to the reaction mixture till pH 2. The temperature of the reaction mixture was raised to 25-35°C and stirred for 12-15 hours. The product was filtered and dried at 25-350C to obtain Form III of (S)-(-)-2-Amino-6-(n- prqpylamino)-4,5,6,7-tetrahydrobenzothiazole.
Example 4: Preparation of Form IV (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (20 g) is dissolved in methanol (500ml) and hydrochloric acid gas is purged at 0-5°C. The reaction mixture is then stirred and filtered, washed with methanol, dried at 4O0C to get (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form IV. The product is filtered, washed and dried at 400C under vacuum (19.9g)
Example 5: Preparation of Form IV Form III of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole (2Q g) was suspended in ethanol (100 ml) and ethanol was recovered completely under reduced pressure at 400C to get (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole Form IV. The product is filtered, washed and dried at 400C under vacuum (19.9g).
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
Brief description of the figures:
Figure 1 represents PXRD graph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form I.
Figure 2 represents PXRD graph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form II.
Figure 3 represents PXRD graph of (S)-(-)-2-Amino~6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form III.
Figure 4 represents PXRD graph of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form IV.

Claims

1. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothia2ole of formula I designated as Form I.
Figure imgf000011_0001
Formula (I)
2. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form I as claimed in claim 1, characterized by PXRD peaks at 9.7, 13.0, 16.6, 18.7, 21.9 ± 0.2°-2θ.
3. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form I as claimed in claim 1 having PXRD pattern as shown in Figure 1.
4. A process for the preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form I comprises treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with solvent selected from acetonitrile, acetone, water and mixtures there of to obtain Form I.
5. A process for preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form I comprises treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with solvent selected from ethyl acetate, dichloro methane, methyl isobutyl ketone and the like to obtain solution and adding anti solvent selected from hexane, diisoproyl ether, diethyl ether, methyl terf-butyl ether, cyclohexane to said solution to obtain Form I.
6. A process for preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form I comprises treating the solution of acid addition salt of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with base to obtain Form I.
7. A process as claimed in claim 6, wherein said acid addition salt of (S)-(-)-2- Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole is preferably hydrochloride or dihydrochloride salt.
8. A process as claimed in claim 6, wherein said base is selected from alkali and alkaline earth metal hydroxide such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, cesium hydroxide and like.
9. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula I designated as Form II.
Figure imgf000012_0001
Formula (I)
10. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form Il as claimed in claim 9, characterized by PXRD peaks at 7.9, 15.8, 19.7, 23.7, 24.4 ± 0.2°-2θ.
11. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form Il as claimed in claim 9 having PXRD pattern as shown in Figure 2
12. A process for preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form Il comprises treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with 0.8 to 1.2 M equivalent hydrochloric acid in alcohol to obtain Form II.
13. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula I designated as Form III.
Figure imgf000012_0002
Formula (I)
14. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazoIe Form III as claimed in claim 13, characterized by PXRD peaks at 12.0, 21.4, 24.2, 24.7, 25.0 ± 0.2°-2θ.
15. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form III as claimed in claim 13 having PXRD pattern as shown in Figure 3
16. A process for preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form III comprises treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with 1.8 to 2.2 M equivalent hydrochloric acid in selective alcohol.
17. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole of formula I designated as Form IV.
Figure imgf000013_0001
Formula (I)
18. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form IV as claimed in claim 17, characterized by PXRD peaks at 15.6, 18.5, 19.9, 20.8, 25.8 ± 0.2°-2θ.
19. (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7-tetrahydrobenzothiazole Form Il as claimed in' claim 17 having PXRD pattern as shown in Figure 4
20. A process for preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form IV comprises treating (S)-(-)-2-Amino-6-(n- propylamino)-4,5,6,7-tetrahydrobenzothiazole with anhydrous selective alcohol to obtain solution , optionally cooling the said solution and passing HCI gas to obtain Form IV.
21. A process for preparation of (S)-(-)-2-Amino-6-(n-propylamino)-4,5,6,7- tetrahydrobenzothiazole Form IV comprises treating Form III of (S)-(-)-2-Amino-6- (n-propylamino)-4,5,6,7-tetrahydrobenzothiazole with selective alcohol to obtain solution and concentrating the solution to obtain Form IV.
22. A process as claimed in any preceding claims, wherein said alcohol is selected from methanol, ethanol, isopropanol, n-propanol, tert-butanol, and mixtures thereof preferably methanol or ethanol.
PCT/IN2006/000377 2005-10-25 2006-09-14 Novel polymorphic forms of (s)-(-)-2-amino-6-(n- propylamino) 4,5,6,7- tetrahydrobenzothiazole WO2007054970A2 (en)

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CN107540632A (en) * 2016-06-27 2018-01-05 江苏神龙药业股份有限公司 A kind of novel crystal forms of Pramipexole Monohydrochloride and preparation method thereof
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CN115073391A (en) * 2022-07-26 2022-09-20 山东京卫制药有限公司 Novel crystal form of pramipexole triphenacetate and preparation method thereof
CN115141161A (en) * 2022-07-26 2022-10-04 山东京卫制药有限公司 Crystal form A of pramipexole xinafoate and preparation method thereof

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CN107540632A (en) * 2016-06-27 2018-01-05 江苏神龙药业股份有限公司 A kind of novel crystal forms of Pramipexole Monohydrochloride and preparation method thereof
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CN115073391A (en) * 2022-07-26 2022-09-20 山东京卫制药有限公司 Novel crystal form of pramipexole triphenacetate and preparation method thereof
CN115141161A (en) * 2022-07-26 2022-10-04 山东京卫制药有限公司 Crystal form A of pramipexole xinafoate and preparation method thereof
WO2024021625A1 (en) * 2022-07-26 2024-02-01 山东京卫制药有限公司 Crystal form a of pramipexole xinafoate salt and preparation method for crystal form a

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