WO2007057919A2 - Procede ameliore pour la preparation de (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine - Google Patents

Procede ameliore pour la preparation de (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine Download PDF

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Publication number
WO2007057919A2
WO2007057919A2 PCT/IN2006/000355 IN2006000355W WO2007057919A2 WO 2007057919 A2 WO2007057919 A2 WO 2007057919A2 IN 2006000355 W IN2006000355 W IN 2006000355W WO 2007057919 A2 WO2007057919 A2 WO 2007057919A2
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WO
WIPO (PCT)
Prior art keywords
formula
methyl
valsartan
hydroxide
butyl
Prior art date
Application number
PCT/IN2006/000355
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English (en)
Other versions
WO2007057919A3 (fr
Inventor
Pandurang Balwant Deshpande
Anand Kumar Pandey
Parven Kumar Luthra
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 WO2007057919A2 publication Critical patent/WO2007057919A2/fr
Publication of WO2007057919A3 publication Critical patent/WO2007057919A3/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 improved process for hydrolysis of N-[(2'-(1 H- Tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeryl-(L)-valine ester derivative of formula (II), henceforth referred as "Valsartan ester derivative” , which is penultimate intermediate for the preparation of Valsartan of formula (I), chemically known as (S)-N-(1-Carboxy-2-methyl-prop-1-yl)-N-pentanoyl-N-[2'-(1 H-tetrazol-5- yl)biphenyl-4-ylmethyl]-amine,
  • Ri represents Ci-C ⁇ alkyl selected from methyl, ethyl, n-propyl, iso- propyl, n-butyl, tert-butyl or 2-methyl-propyl; substituted or unsubstituted phenyl group or like and P is hydrogen or a tetrazole protecting group.
  • 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.
  • the synthesis involves the conversion of 4-bromomethyl-2'-cyanobiphenyl of formula (A) to carbaldehyde of formula (C). Further, it is condensed with methyl ester of L-valine of formula (D) under reducing condition to give N-[(2'- cyanobiphenyl-4-yl)methyl-(L)-valine methyl ester of formula (E), which is purified by flash chromatography. Reaction of compound of formula (E) with n-Valeroyl chloride of formula (F) in presence of triethylamine gives N-valeryl-N-[(2'- cyanobiphenyl-4-yl)methyl-(L)-valine methyl ester or formula (G). After purification by flash chromatography, compound of formula (G) is cyclized in presence of tributyl tin azide in xylene and converted to Valsartan (I) in presence of sodium hydroxide.
  • the carbaldehyde compound (C) is condensed with Tosylate salt of L-valine benzyl ester in presence of sodium cyanoborohydride to give benzyl ester of formula (E).
  • This compound is purified by converting it into its hydrochloride salt and then breaking the hydrochloride salt with sodium bicarbonate. The purified compound is then reacted with n-Valeroyl chloride and cyclized with tributyl tin azide in xylene. Further hydrogenation using Pd-C as catalyst gives Valsartan (I).
  • R is -CH(CH 3 ) 2 in above scheme represents Valsartan (I). It is observed that hydrolysis using alkali metal hydroxides usually take longer reaction times like about 20 to about 30 hours, and hence it is not profitable at commercial scale.
  • the inventors of the present invention have surprisingly found that hydrolysis of compound of formula (II) in presence of phase transfer catalysts reduces the reaction period to a considerable extent.
  • the object of the present invention is to provide an improved process for the preparation of Valsartan of formula (I).
  • Another object of the invention is to provide an improved process for the hydrolysis of compound of formula (II).
  • an improved process for preparation of Valsartan of formula (I), comprising carrying out hydrolysis of Valsartan ester derivative of formula (II) in presence of phase transfer catalyst.
  • Another aspect of the present invention provides an improved process for the hydrolysis of Valsartan ester derivative of formula (II) which has reduced reaction time and provides product with high yield and purity.
  • Ri represents CrC 6 alkyl selected from methyl, ethyl, n-propyl, iso- propyl, n-butyl, tert-butyl or 2-methyl-propyl; substituted or unsubstituted phenyl group or like and P is hydrogen or a tetrazole protecting group.
  • the tetrazole protecting group is selected from trityl, monomethyoxytrityl, dimethoxytrityl, benzhydryl, acyl, benzyl which is unsubstituted or substituted, for example by nitro, such as 4-nitrobenzyl, lower alkoxymethyl, such as methoxy- and ethoxymethyl, lower alkylthiomethyl, such as methylthiomethyl, silyl, such as tri-lower alk ' ylsilyl, for example dimethyl-tert-butyl- and triisopropylsilyl, and 2- cyanoethyl, also lower alkoxy-lower alkoxymethyl, such as 2- methoxyethoxymethyl, benzyloxymethyl, phenacyl or like.
  • the reaction is generally carried out in presence of solvent selected from water, chlorinated solvents, ethers, esters, aromatic hydrocarbons and mixtures thereof, examples of which include dichloro methane, dichloro ethane, chloroform, carbon tetrachloride, tetrahydrofuran, diethyl ether, diisopropyl ether, dimethyl ether, ethyl acetate, butyl acetate, methyl acetate, ethyl formate, methyl formate, benzene, toluene, xylene and like.
  • solvent selected from water, chlorinated solvents, ethers, esters, aromatic hydrocarbons and mixtures thereof, examples of which include dichloro methane, dichloro ethane, chloroform, carbon tetrachloride, tetrahydrofuran, diethyl ether, diisopropyl ether, dimethyl ether, ethyl acetate, butyl
  • the base is selected from group comprising of alkali or alkaline earth metal hydroxides, carbonates or bicarbonates selected from sodium hydroxide, potassium hydroxide, cesium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate and like, preferably sodium hydroxide.
  • the acid is selected from group comprising of HCI, H 2 SO 4 , H 3 PO 4 , acetic acid, formic acid or like.
  • the phase transfer catalyst is selected from crown ethers or quaternary ammonium salts.
  • Quaternary ammonium salts can be aryl and aralkyl ammonium halide examples of which include tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, tetrabutyl ammonium fluoride, tetrabutyl ammonium iodide, cetyl trimethyl ammonium chloride and benzyl trialkyl ammonium chloride or mixtures thereof.
  • the reaction takes place about 1 hour to about 20 hours, more preferably about 5 hours to 15 hours and most preferably about 10 hours to 12 hours.
  • the reaction is carried out at temperature of about 0 0 C to reflux temperature of the solvent, preferably at ambient temperature.
  • the compound of formula (II) is prepared by method known perse of by any method know to person skilled in art.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Catalysts (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé amélioré pour la préparation de valsartan de formule (I), par hydrolyse d'un dérivé d'ester de valsartan de formule (II) en présence d'un catalyseur de transfert de phase.
PCT/IN2006/000355 2005-10-25 2006-09-11 Procede ameliore pour la preparation de (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine WO2007057919A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1335MU2005 2005-10-25
IN1335/MUM/2005 2005-10-25

Publications (2)

Publication Number Publication Date
WO2007057919A2 true WO2007057919A2 (fr) 2007-05-24
WO2007057919A3 WO2007057919A3 (fr) 2007-09-20

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2006/000355 WO2007057919A2 (fr) 2005-10-25 2006-09-11 Procede ameliore pour la preparation de (s)-n-(1-carboxy-2-methyl-prop-1-yl)-n-pentanoyl-n-[2'-(1h-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine

Country Status (1)

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WO (1) WO2007057919A2 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009125416A2 (fr) 2008-04-07 2009-10-15 Hetero Research Foundation Procédé de préparation d'un intermédiaire de valsartan
EP2167477A2 (fr) * 2007-06-27 2010-03-31 Matrix Laboratories Ltd Procédé perfectionné pour préparer du valsartan pur
CN104370961A (zh) * 2014-10-27 2015-02-25 三门峡中达化工有限公司 一种相转移催化水解制备异辛基膦酸单异辛酯的方法
JP2018162313A (ja) * 2012-07-25 2018-10-18 サルコード・バイオサイエンス・インコーポレイテッド Ｌｆａ−１阻害剤およびその多形

Citations (4)

* 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
WO2004026847A1 (fr) * 2002-09-23 2004-04-01 Novartis Ag Procede de fabrication de valsartan
WO2004111018A1 (fr) * 2003-06-16 2004-12-23 Hetero Drugs Limited Nouveau procede de preparation de valsartan
WO2005049586A1 (fr) * 2003-11-24 2005-06-02 Belupo-Lijekovi Kozmetika D.D. Procede de production de (s) n-pentanoyl-n-[[2'-(1h-tetrazole-5yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine

Patent Citations (4)

* 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
WO2004026847A1 (fr) * 2002-09-23 2004-04-01 Novartis Ag Procede de fabrication de valsartan
WO2004111018A1 (fr) * 2003-06-16 2004-12-23 Hetero Drugs Limited Nouveau procede de preparation de valsartan
WO2005049586A1 (fr) * 2003-11-24 2005-06-02 Belupo-Lijekovi Kozmetika D.D. Procede de production de (s) n-pentanoyl-n-[[2'-(1h-tetrazole-5yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2167477A2 (fr) * 2007-06-27 2010-03-31 Matrix Laboratories Ltd Procédé perfectionné pour préparer du valsartan pur
EP2167477A4 (fr) * 2007-06-27 2012-01-18 Matrix Lab Ltd Procédé perfectionné pour préparer du valsartan pur
US8258312B2 (en) 2007-06-27 2012-09-04 Mylan Laboratories Ltd Process for preparing pure valsartan
WO2009125416A2 (fr) 2008-04-07 2009-10-15 Hetero Research Foundation Procédé de préparation d'un intermédiaire de valsartan
US8492577B2 (en) 2008-04-07 2013-07-23 Hetero Research Foundation Process for preparation of valsartan intermediate
JP2018162313A (ja) * 2012-07-25 2018-10-18 サルコード・バイオサイエンス・インコーポレイテッド Ｌｆａ−１阻害剤およびその多形
JP2020128433A (ja) * 2012-07-25 2020-08-27 ノヴァーティス・アーゲー Ｌｆａ−１阻害剤およびその多形
US10906892B2 (en) 2012-07-25 2021-02-02 Novartis Pharmaceuticals Corporation LFA-1 inhibitor and methods of preparation and polymorph thereof
CN104370961A (zh) * 2014-10-27 2015-02-25 三门峡中达化工有限公司 一种相转移催化水解制备异辛基膦酸单异辛酯的方法

Also Published As

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WO2007057919A3 (fr) 2007-09-20

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