WO2007088558A2 - Procédé de purification du valsartan - Google Patents

Procédé de purification du valsartan Download PDF

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Publication number
WO2007088558A2
WO2007088558A2 PCT/IN2007/000021 IN2007000021W WO2007088558A2 WO 2007088558 A2 WO2007088558 A2 WO 2007088558A2 IN 2007000021 W IN2007000021 W IN 2007000021W WO 2007088558 A2 WO2007088558 A2 WO 2007088558A2
Authority
WO
WIPO (PCT)
Prior art keywords
valsartan
solvent
purification
aliphatic hydrocarbon
group
Prior art date
Application number
PCT/IN2007/000021
Other languages
English (en)
Other versions
WO2007088558A3 (fr
Inventor
Pandurang Balwant Deshpande
Parven Kumar Luthra
Anand Kumar Pandey
Hetal Rameshchandra Shah
Original Assignee
Alembic Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alembic Limited filed Critical Alembic Limited
Publication of WO2007088558A2 publication Critical patent/WO2007088558A2/fr
Publication of WO2007088558A3 publication Critical patent/WO2007088558A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings

Definitions

  • the present invention relates to a process for purification of Valsartan of formula
  • Valsartan is chemically known as (S)-N-(I -Carboxy-2-methyl-prop-1-yl)-N- pentanoyl-N-[2'-(1 H-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine, having formula C 24 H29N5O3 and molecular weight 435.52.
  • the current pharmaceutical product containing this drug is being sold by Novartis using the tradename Diovan ® in the form of tablets.
  • Valsartan belongs to group of angiotensin Il antagonists which are useful in the treatment of hypertension, anxiety, glaucoma and cardiac attacks.
  • Valsartan is an orally active specific angiotensin Il antagonist acting on the AT1 receptor subtype. It is useful in regulating high blood pressure and cardiac insufficiency.
  • Valsartan is first disclosed in US Patent No. 5,399,578 which also discusses its process for preparation. The final product is recrystallized from ethyl acetate. Another example in same patent recites recrystallization from diisopropyl ether. However these processes for purification do not give Valsartan with high purity.
  • Valsartan a (1 :1) mixture of ethyl acetate-hexane.
  • crystallization i.e. crystallization by precipitation or slurrying or any the process.
  • it also remains silent about the resultant form of Valsartan.
  • present inventors have directed their research work towards developing a process for purification of Valsartan of high purity i.e. contains [esidual solvent less than the specified limit as given in ICH guideline.
  • the present inventors have found out that if the crude Valsartan crystallized from an organic solvent is washed with aliphatic hydrocarbon solvent and then dried, it reduces the residual solvent level well below as per the FDA requirement. Further, the time taken for drying can also be reduced from several days to several hours.
  • the primary object of the present invention is to provide a process for purification of Valsartan.
  • Another object of the present invention is to provide process for preparation of Valsartan in high purity.
  • Yet another object of the present invention is to provide a process for preparation of Valsartan having purity more than 99%.
  • Another object of the present invention is to provide a process for purification of Valsartan in without any quantitative yield loss.
  • Yet another object of the present invention is to provide Valsartan having residual solvent content below the level as per the International Conference on Harmonization (ICH) guideline.
  • ICH International Conference on Harmonization
  • present invention provides process for purification of Valsartan to obtain valsartan of at least 99% purity, said process comprising steps of: (i) crystallizing from an organic solvent
  • step (ii) washing the crystallized product obtained in step (i) with a solvent selected from a group consisting of aliphatic hydrocarbon solvent.
  • the present invention provides a process for purification of Valsartan to obtain valsartan of at least 99% purity, said process comprising steps of: (i) crystallizing from an organic solvent
  • step ( ⁇ ) washing the crystallized product obtained in step (i) with a solvent selected from a group consisting of aliphatic hydrocarbon solvent.
  • a solvent selected from a group consisting of aliphatic hydrocarbon solvent.
  • the crude Valsartan is dissolved in an organic solvent at elevated temperature preferably at 40 0 C to 6O 0 C.
  • the product is crystallized from the solution either by reducing the volume of the solvent or cooling the solution or both.
  • the cooling temperature ranges from about O 0 C to about 5 0 C.
  • the precipitate formed is isolated by conventional method such as filtration, decantation or centrifugation.
  • the solid is washed with aliphatic hydrocarbon solvent.
  • the product obtained after washing with aliphatic hydrocarbon solvent i.e. n-pentane is in amorphous form.
  • organic solvent comprises ester, ketone, ether, nitrile, alcohol, chlorinated solvent and the like or mixture thereof.
  • organic solvent examples include but not limited to ethylacetate, acetone, diisopropylether, acetonitrile, methanol, ethanol, propanol, chloroform, dichloromethane, dichloroethane and the like or mixture thereof.
  • crystallization refers to any method known to a person skilled in the art such as crystallization from single solvent or combination of solvents by dissolving the compound optionally at elevated temperature and precipitating the compound by cooling the solution or removing solvent from the solution or both. It further includes methods such as solvent/antisolvent or precipitation.
  • aliphatic hydrocarbon solvent examples include but are not limited to n- pentane, n-heptane, hexane, cyclohexane, octane and the like or mixture thereof.
  • Valsartan having purity of more than 99% and having residual ethyl acetate content within expectable limits of regulatory authorities.
  • the comparison data obtained for the final product before and after washing with the n-pentane with respect to residual ethyl acetate content is given in the table below.
  • Ethylacetate, methylacetate, propylacetate, heptane, pentane, acetone, methylethylketone, tetrahydrofuaran comes under Class 3 category of solvents.
  • Class 3 solvent content in a product is restricted up to 5000ppm as per the ICH guideline.
  • Valsartan Calcium 120 gm was suspended in a mixture of Dl water (700 ml) and ethyl acetate (1000 ml) and treated with hydrochloric acid to adjust pH 1.5-2.5. The organic layer was separated and washed with water and concentrated to a solid residue material. Ethyl acetate (600 ml) was added to the residue and heated to get clear solution. The solution was cooled slowly under stirring to 0- 5°C to get thick slurry. The solid is filtered. The wet solid was transferred to another RB Flask and n-Pentane (840ml) was added and stirred.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention porte sur un procédé de purification du Valsartan consistant: (i) à le cristalliser à partir d'un solvant organique; et (ii) à laver le produit cristallisé obtenu en (i) au moyen d'un solvant choisi parmi des hydrocarbures aliphatiques.
PCT/IN2007/000021 2006-02-02 2007-01-19 Procédé de purification du valsartan WO2007088558A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN164MU2006 2006-02-02
IN164/MUM/2006 2006-02-02

Publications (2)

Publication Number Publication Date
WO2007088558A2 true WO2007088558A2 (fr) 2007-08-09
WO2007088558A3 WO2007088558A3 (fr) 2007-10-25

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2007/000021 WO2007088558A2 (fr) 2006-02-02 2007-01-19 Procédé de purification du valsartan

Country Status (1)

Country Link
WO (1) WO2007088558A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007017897A3 (fr) * 2005-05-25 2009-10-15 Ipca Laboratories Ltd. Nouvelles formes cristallines de (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)bi-phenyl-4-ylmethyl]-amine
CN102329276A (zh) * 2011-09-30 2012-01-25 浙江新赛科药业有限公司 一种缬沙坦母液的回收方法
CN103435567A (zh) * 2013-09-09 2013-12-11 山东新华制药股份有限公司 缬沙坦的精制方法
CN103739564A (zh) * 2012-02-20 2014-04-23 中国科学院上海药物研究所 缬沙坦的多晶型及其制备方法
CN104030996A (zh) * 2014-05-21 2014-09-10 丽珠医药集团股份有限公司 一种缬沙坦的合成方法
CN108047152A (zh) * 2017-12-12 2018-05-18 湖南千金协力药业有限公司 一种缬沙坦的精制方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5399578A (en) * 1990-02-19 1995-03-21 Ciba-Geigy Corp Acyl compounds
WO2003089417A1 (fr) * 2002-04-15 2003-10-30 Dr. Reddy's Laboratories Limited Nouvelles formes cristallines de (s)-n-(1-carboxy-2-methyl-prop-1-yl) -n-pentanoyl-n- [2'-(1h-tetrazol-5-yl-)- biphenyl-4-yl methyl] amine (valsartan)
WO2005049587A1 (fr) * 2003-11-21 2005-06-02 Ranbaxy Laboratories Limited Procede de preparation de tetrazole de biphenyle
US20060149079A1 (en) * 2005-01-03 2006-07-06 Padi Pratap R Process for preparing valsartan
EP1714963A1 (fr) * 2005-04-19 2006-10-25 IPCA Laboratories Limited Procédé pour la préparation du Valsartan et de ses intermédiaires

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5399578A (en) * 1990-02-19 1995-03-21 Ciba-Geigy Corp Acyl compounds
WO2003089417A1 (fr) * 2002-04-15 2003-10-30 Dr. Reddy's Laboratories Limited Nouvelles formes cristallines de (s)-n-(1-carboxy-2-methyl-prop-1-yl) -n-pentanoyl-n- [2'-(1h-tetrazol-5-yl-)- biphenyl-4-yl methyl] amine (valsartan)
WO2005049587A1 (fr) * 2003-11-21 2005-06-02 Ranbaxy Laboratories Limited Procede de preparation de tetrazole de biphenyle
US20060149079A1 (en) * 2005-01-03 2006-07-06 Padi Pratap R Process for preparing valsartan
EP1714963A1 (fr) * 2005-04-19 2006-10-25 IPCA Laboratories Limited Procédé pour la préparation du Valsartan et de ses intermédiaires

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MOENIUS TH ET AL: "Carbon-14 labelling of DIOVAN(TM) in its valine-moiety" 2000, JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS 2000 UNITED KINGDOM, VOL. 43, NR. 13, PAGE(S) 1245-1252 , XP002442573 ISSN: 0362-4803 cited in the application page 1249 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007017897A3 (fr) * 2005-05-25 2009-10-15 Ipca Laboratories Ltd. Nouvelles formes cristallines de (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)bi-phenyl-4-ylmethyl]-amine
CN102329276A (zh) * 2011-09-30 2012-01-25 浙江新赛科药业有限公司 一种缬沙坦母液的回收方法
CN102329276B (zh) * 2011-09-30 2013-09-25 浙江新赛科药业有限公司 一种缬沙坦母液的回收方法
CN103739564A (zh) * 2012-02-20 2014-04-23 中国科学院上海药物研究所 缬沙坦的多晶型及其制备方法
CN103435567A (zh) * 2013-09-09 2013-12-11 山东新华制药股份有限公司 缬沙坦的精制方法
CN104030996A (zh) * 2014-05-21 2014-09-10 丽珠医药集团股份有限公司 一种缬沙坦的合成方法
CN104030996B (zh) * 2014-05-21 2016-06-01 丽珠医药集团股份有限公司 一种缬沙坦的合成方法
CN108047152A (zh) * 2017-12-12 2018-05-18 湖南千金协力药业有限公司 一种缬沙坦的精制方法

Also Published As

Publication number Publication date
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