WO2011021214A2 - Procédé amélioré pour la préparation de (s)-2-amino-4,5,6,7-tétrahydro-6-(propylamino)benzothiazole et de ses sels pharmaceutiquement acceptables - Google Patents

Procédé amélioré pour la préparation de (s)-2-amino-4,5,6,7-tétrahydro-6-(propylamino)benzothiazole et de ses sels pharmaceutiquement acceptables Download PDF

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Publication number
WO2011021214A2
WO2011021214A2 PCT/IN2010/000521 IN2010000521W WO2011021214A2 WO 2011021214 A2 WO2011021214 A2 WO 2011021214A2 IN 2010000521 W IN2010000521 W IN 2010000521W WO 2011021214 A2 WO2011021214 A2 WO 2011021214A2
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WO
WIPO (PCT)
Prior art keywords
formula
compound
tetrahydrobenzo
acid
pramipexole
Prior art date
Application number
PCT/IN2010/000521
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English (en)
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WO2011021214A3 (fr
Inventor
Manne Satyanarayana Reddy
Sajja Eswaraiah
Maramreddy Sahadeva Reddy
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Msn Laboratories Limited
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Publication date
Application filed by Msn Laboratories Limited filed Critical Msn Laboratories Limited
Publication of WO2011021214A2 publication Critical patent/WO2011021214A2/fr
Publication of WO2011021214A3 publication Critical patent/WO2011021214A3/fr

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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 an improved process for the preparation of (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole and its pharmaceutically acceptable salts.
  • 2-amino-4,5,6,7-tetrahydro-6-(propylamino) benzothiazole is commonly known as pramipexole.
  • Pramipexole dihydrochloride monohydrate is represented by the following structural formula- Ia
  • Pramipexole dihydrochlride monohydrate is indicated for the treatment of signs and symptoms of idiopathic Parkinson's disease and is commercially available under the brand name of Mirapex® .
  • Pramipexole and its pharmaceutically acceptable salts are disclosed in US 4886812. This patent also describes the synthesis of pramipexole dihydrochloride, which involves the reaction of bromine with 4-acetylamido-cyclohexanone in glacial acetic acid, followed by the addition of thiourea under reflux conditions to provide
  • J.Med, chem. 1987, 30, 494-498 also disclosed a process for the resolution of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole using L(+)-tartaric acid in water medium.
  • the resolved (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole is treated with triethylamine, propionic anhydride in THF to provide (+)-2-amino-6- priopionamidotetrahydrobenzothiazole, which is then reduced with borane- tetrahydrofuran complex followed by treatment with aqueous hydrochloric acid to provide the desired isomer of pramipexole dihydrochloride monohydrate.
  • the present invention provides an improved process for the preparation of pramipexole dihydrochloride monohydrate with high yield and purity.
  • the first aspect of the present invention is to provide an improved process for the preparation of (S)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine compound of formula-5, an intermediate in the preparation of pramipexole dihydrochloride.
  • the process comprises of the following steps,
  • the second aspect of the present invention is to provide an improved process for the preparation of pramipexole dihydrochloride monohydrate compound of fomula-la, which comprises of the following steps,
  • the third and fourth aspect of the present invention is to provide an improved process for the purification of compound of formula-6 and compound of formula- 1 by acid/base or base/acid treatment.
  • Figure-1 Illustrates the powder X-ray diffraction pattern of pramipexole dihydrochloride monohydrate.
  • Figure-2 Illustrates the IR spectrum of pramipexole dihydrochloride monohydrate
  • Figure-3 Illustrates the DSC thermogram of pramipexole dihydrochloride monohydrate
  • Figure-4 Illustrates the powder X-ray diffraction pattern of pramipexole free base obtained as per the prior art process.
  • the present invention relates to an improved process for the preparation of pramipexole dihydrochloride monohydrate compound of formula- Ia.
  • the first aspect of the present invention provides an improved process for the preparation of (S)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine compound of formula-5,
  • (S)-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine compound of formula-5 involves the isolation and crystallization of N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6- yl)acetamide hydrobromide compound of formula-3 from a suitable ketone solvent like acetone.
  • the second aspect of the present invention provides an improved process for the preparation of pramipexole dihydrochloride monohydrate compound of fomula-la,
  • the third aspect of the present invention provides a process for the purification of pramipexole compound of formula- 1, which comprises of the following steps, a) Suspending pramipexole in a suitable alcoholic solvents like methanol, ethanol, isopropanol, n-propanol, butanol or aqueous alcohols or water or mixtures thereof, b) acidifying the above suspension using suitable acid to form a solution,
  • a suitable solvents selected ester solvents like ethyl acetate, isopropyl acetate; chloro solvents like methylenechloride, chloroform and hydrocarbon solvents like toluene, heptane, hexane and cyclohexane, e) stirring the said solution;
  • the fourth aspect of the present invention provides a process for the purification of N-((S)-2-arnino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl) propionamide compound of formula-6, which comprises of the following steps,
  • Further aspect of the present invention provides a process for the purification of pramipexole compound of formula- 1, which comprises of the following steps, a) Suspending pramipexole in a suitable alcoholic solvents like methanol, ethanol, isopropanol, n-propanol, butanol or aqueous alcohols or mixtures thereof, preferably isopropyl alcohol,
  • a suitable alcoholic solvents like methanol, ethanol, isopropanol, n-propanol, butanol or aqueous alcohols or mixtures thereof, preferably isopropyl alcohol,
  • the suitable acid used as per any aspect of the present invention is selected from hydrochloric acid, hydrobromic acid, acetic acid, benzenesulfonic acid, camphoursulfonic acid, ethanesulfonic acid, fumaric acid, maleic acid, methane sulfonic acid, oxalicacid, phosphoric acid and sulfuric acid.
  • the suitable base used as per any aspect of the present invention is selected from sodium hydroxide, calcium hydroxide, magnesium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, sodium bicarbonate, potassium bicarbonate and ammonia.
  • the pramipexole or its pharmaceutically acceptable salts can be micronised or milled to get the desired particle size.
  • the pramipexole dihydrochloride monohydrate is prepared as per the prior art process having mean particle size approximately less than 150 microns.
  • the powder X-ray diffractogram & Infrared spectrum of pramipexole hydrochloride monohydrate prepared as per the process disclosed in Journal of Medicinal Chemistry, 1987, 30, 494-498 is shown in figure- 1 & figure-2 respectively.
  • the PXRD and IR spectrum of pramipexole dihydrochloride monohydrate prepared as per the present invention is similar to the PXRD and IR shown in the figure 1 & 2 respectively.
  • the PXRD of pramipexole prepared as per the present invention is similar to the PXRD shown in figure-4.
  • the related substance of pramipexole and its pharmaceutically acceptable salts were analyzed by HPLC using the following conditions: Column: Symmetry C 18, 250 X 4.6 mm, 5 ⁇ m; Flow rate: 0.8 ml/min; wavelength: 265 nm; Temperature: 45°C; Load: 20 ⁇ l; Run time: 55 min; and using buffer (potassium dihydroggen sulphate & octane- 1 -sulfonic acid in water) and acetonitrile in 75:25 v/v ratio as a diluent.
  • buffer potassium dihydroggen sulphate & octane- 1 -sulfonic acid in water
  • the present invention is schematically represented as follows:
  • Acetone 200 ml was added to the wet compound of formula-3 obtained as per example-1 before drying was heated to reflux and stirred for 45 minutes. The reaction mixture was cooled to 25-30°C and stirred for an hour. The obtained solid was filtered, washed with acetone and dried to get the title compound.
  • the wet solid was dissolved in aqueous hydrochloric acid (40 ml hydrochloric acid in 100 ml of water) and subjected to carbon treatment.
  • the reaction mixture was filtered through hyflow and aqueous potassium hydroxide (112 gram potassium hydroxide in 160 ml of water) was added to it.
  • the reaction mixture was stirred for 90 minutes at 25-30°C.
  • the solid obtained was filtered, washed with water and dried to get the title compound
  • Example-8 Purification of N-((S)-2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl) propionamide compound of formula-6:
  • Ethyl acetate 600 ml was added to the reaction mixture and basified with aqueous sodium hydroxide. The reaction mixture was filtered and separated the organic and aqueous layer from filtrate. Aqueous layer was extracted with ethyl acetate and the combined organic layer was distilled off completely under reduced pressure at below 60°C. n-heptane (100 ml) was added to residue and distilled off. N- heptane (250 ml) was added to the obtained residue and stirred for 45 minutes at 25- 30°C. The solid was filtered, washed with heptane and then dried.
  • the compound initially air dried for 2 hours and then dried at 50-55°C to get the .title compound.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un procédé amélioré pour la préparation de (S)-2-amino-4,5,6,7-tétrahydro-6-(propylamino)benzothiazole et de ses sels pharmaceutiquement acceptables. L'invention concerne spécifiquement le composé représenté par la formule développée suivante - Ia.
PCT/IN2010/000521 2009-08-07 2010-08-05 Procédé amélioré pour la préparation de (s)-2-amino-4,5,6,7-tétrahydro-6-(propylamino)benzothiazole et de ses sels pharmaceutiquement acceptables WO2011021214A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1881/CHE/2009 2009-08-07
IN1881CH2009 2009-08-07

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WO2011021214A2 true WO2011021214A2 (fr) 2011-02-24
WO2011021214A3 WO2011021214A3 (fr) 2011-04-28

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104049475A (zh) * 2014-05-30 2014-09-17 青岛华仁技术孵化器有限公司 具有防腐蚀功效的去除剂
CN104496936A (zh) * 2015-01-07 2015-04-08 海南康虹医药科技开发有限公司 一种盐酸普拉克索的制备方法
WO2015155704A1 (fr) * 2014-04-09 2015-10-15 Piramal Enterprises Limited Procédé amélioré de préparation du monohydrate du dichlorhydrate de pramipexole
CN105753812A (zh) * 2016-03-28 2016-07-13 赤峰赛林泰药业有限公司 盐酸普拉克索中间体的合成方法
CN107382904A (zh) * 2017-08-17 2017-11-24 山东新华制药股份有限公司 普拉克索的一种新晶型及其制备方法
CN110878067A (zh) * 2019-11-13 2020-03-13 上海星酶生物科技有限公司 一种二氨基-4,5,6,7-四氢苯并噻唑的结晶工艺
CN110950819A (zh) * 2018-09-27 2020-04-03 湖南九典制药股份有限公司 一种普拉克索制备方法
CN111187232A (zh) * 2020-01-17 2020-05-22 润都制药(武汉)研究院有限公司 一种一锅法合成盐酸普拉克索关键中间体的方法
CN111362884A (zh) * 2018-12-26 2020-07-03 江苏神龙药业股份有限公司 一种2,6-二氨基-4,5,6,7-四氢-苯并噻唑的工业化制备方法
CN112279817A (zh) * 2020-10-26 2021-01-29 珠海润都制药股份有限公司 一种高纯度盐酸普拉克索的制备方法

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GB2394951A (en) * 2002-11-04 2004-05-12 Cipla Ltd One pot synthesis of 2,6-diamino-4,5,6,7-tetrahydro-benzothiazole
WO2005092871A2 (fr) * 2004-03-19 2005-10-06 Dipharma S.P.A. Intermediaires pour la preparation de pramipexole
WO2006012276A1 (fr) * 2004-06-30 2006-02-02 Amr Technology, Inc. Processus pour préparer des 2-amino-6-(alkyl)amino-4,5,6,7-tétrahydrobenzothiazoles chiralement purs par résolution chromatographique en phase liquide
CN1834092A (zh) * 2005-03-15 2006-09-20 姜能桥 盐酸普拉克索的制备方法
CN101429173A (zh) * 2007-11-09 2009-05-13 重庆医药工业研究院有限责任公司 一种普拉克索中间体2,6-二氨基-4,5,6,7-四氢-苯并噻唑的制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2394951A (en) * 2002-11-04 2004-05-12 Cipla Ltd One pot synthesis of 2,6-diamino-4,5,6,7-tetrahydro-benzothiazole
WO2005092871A2 (fr) * 2004-03-19 2005-10-06 Dipharma S.P.A. Intermediaires pour la preparation de pramipexole
WO2006012276A1 (fr) * 2004-06-30 2006-02-02 Amr Technology, Inc. Processus pour préparer des 2-amino-6-(alkyl)amino-4,5,6,7-tétrahydrobenzothiazoles chiralement purs par résolution chromatographique en phase liquide
CN1834092A (zh) * 2005-03-15 2006-09-20 姜能桥 盐酸普拉克索的制备方法
CN101429173A (zh) * 2007-11-09 2009-05-13 重庆医药工业研究院有限责任公司 一种普拉克索中间体2,6-二氨基-4,5,6,7-四氢-苯并噻唑的制备方法

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015155704A1 (fr) * 2014-04-09 2015-10-15 Piramal Enterprises Limited Procédé amélioré de préparation du monohydrate du dichlorhydrate de pramipexole
CN104049475B (zh) * 2014-05-30 2017-12-12 江苏弘汉生物科技有限公司 具有防腐蚀功效的去除剂
CN104049475A (zh) * 2014-05-30 2014-09-17 青岛华仁技术孵化器有限公司 具有防腐蚀功效的去除剂
CN104496936A (zh) * 2015-01-07 2015-04-08 海南康虹医药科技开发有限公司 一种盐酸普拉克索的制备方法
CN105753812A (zh) * 2016-03-28 2016-07-13 赤峰赛林泰药业有限公司 盐酸普拉克索中间体的合成方法
CN107382904A (zh) * 2017-08-17 2017-11-24 山东新华制药股份有限公司 普拉克索的一种新晶型及其制备方法
CN110950819A (zh) * 2018-09-27 2020-04-03 湖南九典制药股份有限公司 一种普拉克索制备方法
CN111362884A (zh) * 2018-12-26 2020-07-03 江苏神龙药业股份有限公司 一种2,6-二氨基-4,5,6,7-四氢-苯并噻唑的工业化制备方法
CN110878067A (zh) * 2019-11-13 2020-03-13 上海星酶生物科技有限公司 一种二氨基-4,5,6,7-四氢苯并噻唑的结晶工艺
CN111187232A (zh) * 2020-01-17 2020-05-22 润都制药(武汉)研究院有限公司 一种一锅法合成盐酸普拉克索关键中间体的方法
CN111187232B (zh) * 2020-01-17 2023-09-29 润都制药(武汉)研究院有限公司 一种一锅法合成盐酸普拉克索关键中间体的方法
CN112279817A (zh) * 2020-10-26 2021-01-29 珠海润都制药股份有限公司 一种高纯度盐酸普拉克索的制备方法
CN112279817B (zh) * 2020-10-26 2023-04-28 珠海润都制药股份有限公司 一种高纯度盐酸普拉克索的制备方法

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