WO2007135693A2 - Intermédiaires utiles pour la préparation d'un dérivé de la pipéridine antihistaminique - Google Patents

Intermédiaires utiles pour la préparation d'un dérivé de la pipéridine antihistaminique Download PDF

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Publication number
WO2007135693A2
WO2007135693A2 PCT/IN2007/000201 IN2007000201W WO2007135693A2 WO 2007135693 A2 WO2007135693 A2 WO 2007135693A2 IN 2007000201 W IN2007000201 W IN 2007000201W WO 2007135693 A2 WO2007135693 A2 WO 2007135693A2
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WO
WIPO (PCT)
Prior art keywords
formula
derivative
methyl
acid
ester
Prior art date
Application number
PCT/IN2007/000201
Other languages
English (en)
Other versions
WO2007135693A3 (fr
Inventor
Chidambaram Venkateswaran Srinivasan
Perminder Singh Johar
Lalit Wadhwa
Original Assignee
Ind-Swift Laboratories 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 Ind-Swift Laboratories Limited filed Critical Ind-Swift Laboratories Limited
Publication of WO2007135693A2 publication Critical patent/WO2007135693A2/fr
Publication of WO2007135693A3 publication Critical patent/WO2007135693A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Definitions

  • the phase transfer catalyst comprises arylalkylammonium halide, tetraalkyl ammonium halide, phosphonium salts and preferably benzyltrietliylammonium chloride is used.
  • the reaction is carried out in any solvent like hydrocarbons such as benzene, toluene, xylene; chlorinated hydrocarbon such as methylene chloride and the like; acetates such as ethyl acetate; ethers such as dioxane, tetrahydrofuran; acetonitrile, dimethylacetamide, dimethylformamide, n- methylpyrrolidine, dimethylsulfoxide and the like, at a temperature ranging from ambient temperature to 8O 0 C.
  • the crude product can be purified by preparing acid addition salts.
  • the acid can be any suitable acid such as citric acid, fumaric acid, maleic acid, pthalic acid, isopthalic acid, p-terepthalic acid, oxalic acid and the like.
  • keto ester of the formula IX is reduced first with the help of reducing agent such as sodium borohydride and thereafter hydroxyl ester is hydrolyzed to fexofenadine in situ or optionally by isolating the corresponding hydroxyl ester intermediate.
  • keto ester of the formula IX can be hydrolyzed first and thereafter keto group is reduced to hydroxyl to form fexofenadine which is converted to fexofenadine salts such as hydrochloride having purity greater than 99.5%.
  • Major advantages realized in the present invention is that process provides exclusively para isomer thus no need of extensive purification and affords fexofenadine hydrochloride in high purity.
  • Demineralized water (20 ml) was added slowly at 50-55 0 C and stirred for 30 minutes. The reaction mixture was cooled and stirred. The product obtained was filtered, washed with demineralized water and dried at 50-55 0 C for 6-8 hours to obtain 9.0 g of 2-(4- ⁇ l-hydroxy-4-[4- (hydroxyl -diplienyl-methyl)-piperidin- 1 -yl] -butyl ⁇ -phenyl )-2-methyl-propionic acid methyl ester.

Landscapes

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

Abstract

La présente invention concerne un procédé de préparation d'un dérivé de la pipéridine antihistaminique, notamment la fexofénadine et ses sels pharmaceutiquement acceptables, par l'utilisation de nouveaux intermédiaires synthétiques de formule (I) suivante, où R représente un alkyle inférieur ; R2 représente H, un cyclopropyle, R1 représente un alkyle, la 4-(hydroxy-diphényl-méthyl)-pipéridin-1-yle.
PCT/IN2007/000201 2006-05-18 2007-05-18 Intermédiaires utiles pour la préparation d'un dérivé de la pipéridine antihistaminique WO2007135693A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1219/DEL/2006 2006-05-18
IN1219DE2006 2006-05-18

Publications (2)

Publication Number Publication Date
WO2007135693A2 true WO2007135693A2 (fr) 2007-11-29
WO2007135693A3 WO2007135693A3 (fr) 2009-06-11

Family

ID=38723705

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2007/000201 WO2007135693A2 (fr) 2006-05-18 2007-05-18 Intermédiaires utiles pour la préparation d'un dérivé de la pipéridine antihistaminique

Country Status (1)

Country Link
WO (1) WO2007135693A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7671071B2 (en) 2002-06-10 2010-03-02 Teva Pharmaceutical Industries Ltd. Polymorphic Form XVI of fexofenadine hydrochloride
CN102757382A (zh) * 2012-07-06 2012-10-31 启东东岳药业有限公司 非索非那定中间体的纯化方法
WO2017068129A1 (fr) 2015-10-22 2017-04-27 Sanofi-Aventis Deutschland Gmbh Procédé de préparation de fexofénadine et d'intermédiaires utilisés dans celle-ci

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5750703A (en) * 1993-06-24 1998-05-12 Albany Molecular Research, Inc. Piperidine derivatives and process for their production
US6147217A (en) * 1997-02-04 2000-11-14 Sepracor Inc. Synthesis of terfenadine and derivatives
WO2002102776A1 (fr) * 2001-06-15 2002-12-27 Aventis Pharma Deutschland Gmbh Procede de production du derive fexofenadine de piperidine
WO2004054955A1 (fr) * 2002-12-16 2004-07-01 Ranbaxy Laboratories Limited Procede de preparation de la fexofenadine

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5750703A (en) * 1993-06-24 1998-05-12 Albany Molecular Research, Inc. Piperidine derivatives and process for their production
US6147217A (en) * 1997-02-04 2000-11-14 Sepracor Inc. Synthesis of terfenadine and derivatives
WO2002102776A1 (fr) * 2001-06-15 2002-12-27 Aventis Pharma Deutschland Gmbh Procede de production du derive fexofenadine de piperidine
WO2004054955A1 (fr) * 2002-12-16 2004-07-01 Ranbaxy Laboratories Limited Procede de preparation de la fexofenadine

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7671071B2 (en) 2002-06-10 2010-03-02 Teva Pharmaceutical Industries Ltd. Polymorphic Form XVI of fexofenadine hydrochloride
CN102757382A (zh) * 2012-07-06 2012-10-31 启东东岳药业有限公司 非索非那定中间体的纯化方法
WO2017068129A1 (fr) 2015-10-22 2017-04-27 Sanofi-Aventis Deutschland Gmbh Procédé de préparation de fexofénadine et d'intermédiaires utilisés dans celle-ci
US10696633B2 (en) 2015-10-22 2020-06-30 Sanofi-Aventis Deutschland Gmbh Process for the preparation of fexofenadine and of intermediates used therein

Also Published As

Publication number Publication date
WO2007135693A3 (fr) 2009-06-11

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