WO2007088558A2 - Procédé de purification du valsartan - Google Patents

Procédé de purification du valsartan Download PDF

Info

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
Legal status (The legal status 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 status listed.)
Ceased
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
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alembic Ltd
Original Assignee
Alembic Ltd
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 Ltd filed Critical Alembic Ltd
Publication of WO2007088558A2 publication Critical patent/WO2007088558A2/fr
Publication of WO2007088558A3 publication Critical patent/WO2007088558A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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.

Landscapes

  • 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 Ceased 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

ID=38229031

Family Applications (1)

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

Country Status (1)

Country Link
WO (1) WO2007088558A2 (fr)

Cited By (7)

* 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
CN116672321A (zh) * 2023-06-08 2023-09-01 海南皇隆制药股份有限公司 一种提高缬沙坦片质量的生产工艺

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL97219A (en) * 1990-02-19 1995-12-08 Ciba Geigy Ag Biphenyl substituted aliphatic amino compounds process for their preparation and pharmaceutical compositions containing them
AU2003223637A1 (en) * 2002-04-15 2003-11-03 Dr. Reddy's Laboratories Limited Novel crystalline forms of (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
US7659406B2 (en) * 2005-01-03 2010-02-09 Dr. Reddy's Laboratories Limited 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

Cited By (9)

* 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
CN116672321A (zh) * 2023-06-08 2023-09-01 海南皇隆制药股份有限公司 一种提高缬沙坦片质量的生产工艺

Also Published As

Publication number Publication date
WO2007088558A3 (fr) 2007-10-25

Similar Documents

Publication Publication Date Title
JP6591944B2 (ja) ナルメフェン塩酸塩二水和物
WO2007088558A2 (fr) Procédé de purification du valsartan
CN103930419B (zh) 阿齐沙坦的晶型及其制备方法
US20110282069A1 (en) High-purity febuxostat and the method for preparation
US7196222B2 (en) Sertraline hydrochloride form II and methods for the preparation thereof
CA3060121A1 (fr) Polymorphe de compose, procede de preparation s'y rapportant et utilisation de celui-ci
CN109761924B (zh) 一种改进的缬沙坦反应混合液的后处理方法
CN102391200A (zh) 一种高纯度缬沙坦的制备方法
CN114040906A (zh) 帕拉米韦三水合物的新制备方法及其水系干燥
WO2005049587A1 (fr) Procede de preparation de tetrazole de biphenyle
US9815801B2 (en) Method of refining valsartan comprising more than or equal to 10% D-isomers
WO2009046581A1 (fr) Procédé de résolution d'acide (6r,s)-5-formyltetrahydrofolique et sa salification
WO2010091169A2 (fr) Préparation de valsartan
CN114845713A (zh) 制备高纯度缬沙坦的方法
EP2041083B1 (fr) Procédé de préparation de zofénopril calcium
CZ20031360A3 (cs) Způsob výroby N-(1-oxopentyl)-N-[[2´-(1H-tetrazol-5-yl)[1,1´-bifenyl]-4-yl]methyl]-L-valinu(valsartanu)
US20110171300A1 (en) Delta 9 tetrahydrocannabinol derivatives
EP2167477B1 (fr) Procédé pour préparer du valsartan pur
JP3883525B2 (ja) プラバスタチンナトリウムの精製方法
HRP20030631A2 (en) An improved process for preparing pure ondansetron hydrocloride dihydrate
AU2002236753A1 (en) An improved process for preparing pure ondansetron hydrochloride dihydrate
CN116813564B (zh) 一种缬沙坦的合成精制方法
WO2007069271A2 (fr) Procede de purification d'une (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine
WO2011000396A1 (fr) Purification d'un intermédiaire du létrozole
CN115141158A (zh) 一种缬沙坦的制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07736499

Country of ref document: EP

Kind code of ref document: A2