WO2007144729A1 - Procédé amélioré pour la préparation de clopidogrel - Google Patents

Procédé amélioré pour la préparation de clopidogrel Download PDF

Info

Publication number
WO2007144729A1
WO2007144729A1 PCT/IB2007/001542 IB2007001542W WO2007144729A1 WO 2007144729 A1 WO2007144729 A1 WO 2007144729A1 IB 2007001542 W IB2007001542 W IB 2007001542W WO 2007144729 A1 WO2007144729 A1 WO 2007144729A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
clopidogrel
preparation
iii
chlorophenyl
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/IB2007/001542
Other languages
English (en)
Inventor
Chandrasekaran Ramasubbu
Rajanikanth Mamidala
Desinghu Arjunan
Karthik Ramasamy
Mahender Rao Siripragada
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.)
Orchid Pharma Ltd
Original Assignee
Orchid Chemicals and Pharmaceuticals 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 Orchid Chemicals and Pharmaceuticals Ltd filed Critical Orchid Chemicals and Pharmaceuticals Ltd
Publication of WO2007144729A1 publication Critical patent/WO2007144729A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to an improved process for the preparation of Clopidogrel of formula (I). More particularly, the present invention relates to an improved process for the preparation of Clopidogrel intermediate of formula (III) using triethylamine as an organic base in the absence of an organic solvent.
  • Clopidogrel which is chemically known as (+)-(5)-2-(2-Chlorophenyl)-2- (4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetic acid methyl ester is a P 2 Yi 2 (P 2 T) antagonists, and has the following structural formula:
  • Clopidogrel bisulfate is useful in antiplatelet and atherosclerosis therapy as an anti-thrombotic and marketed under the trade name Plavix ® by Sanof ⁇ -Aventis.
  • Clopidogrel is disclosed in U.S. Pat. Nos. 4,529,596, 6,258,961, 5,036,156, 6,080,875, 6,180,793 all of which are incorporated herein by reference for their disclosure and preparation of Clopidogrel.
  • U.S. Pat. No. 4,529,596 discloses a racemic mixture of Clopidogrel and processes for preparing such mixture.
  • the enantiomer ( ⁇ -Clopidogrel is particularly preferred since it is the pharmaceutically active compound.
  • U.S. Pat. No. 5,204,469 discloses an enantioselective process for synthesis of Clopidogrel through reaction of (+)-2-(Chlorophenyl) glycine and an activated form of 2-thiopheneethanol in the presence of an organic solvent using organic and inorganic base followed by cyclization with aqueous formaldehyde.
  • the main objective of the present invention is to provide an improved process for the preparation of compound of formula (III) using triethylamine as an organic base in the absence of an organic solvent.
  • Another objective of the present invention is to provide a process for the preparation of compound of formula (I), which would be easy to implement on commercial scale, which can avoid the use of toxic solvent (s) like tetrahydrofuran, methylene chloride, dimethylformamide, toluene etc.
  • toxic solvent s
  • Another objective of the present invention is the optional in-situ preparation of
  • Still another objective of the present invention is to provide a process for the preparation of compound of formula (I) in good yield and high stereo-chemical purity.
  • the present invention provides an improved process for the preparation of Clopidogrel of formula (I) and its pharmaceutically acceptable salts, which comprises the steps of;
  • step (c) converting Clopidogrel of. formula (I) as obtained in step (b) to the pharmaceutically acceptable salts thereof by conventional methods.
  • reaction step is performed in absence of an organic solvent.
  • the organic base used for the reaction step is such as an alkylamine base which includes triethylamine, diethylamine, N,N-diethyl methylamine, N,N-diethyl aniline, N,N-diethylethylenediamine, or N 5 N- diisopropylethylamine, dimethylaminopyridine, diisopropylethylamine, N- methylmorpholine, N-methylpyrrolidine, 2,6-di-tertbutyl-4-methylpyridine, pyridine and the like, the most preferred base for this reaction is triethyl amine.
  • the reaction step is performed at a temperature in the range of 20 0 C to 100 0 C, more preferably the reacting step is performed at temperature in the range of 78 0 C to 82 0 C.
  • the duration of the reaction is only 10 to 12 hrs as against the 30 hrs mentioned in the prior art .
  • the starting materials are prepared according to the literature available in the prior art.
  • Methyl(25)-(+)-(2-chlorophenyl)-N-[2-(2-thieno)ethyl] glycinate (10 gm ,0.032 mole) was treated with aqueous formaldehyde (30% , 50 ml), heated to 60 0 C to get clear solution and maintained for 20 to 30 mins.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

La présente invention concerne un procédé amélioré pour la préparation de clopidogrel de formule (I). Plus particulièrement, la présente invention concerne un procédé amélioré pour la préparation d'intermédiaire de clopidogrel de formule (III) utilisant la triéthylamine en tant que base organique en l'absence d'un solvant organique. Formule (I), Formule (III).
PCT/IB2007/001542 2006-06-13 2007-06-08 Procédé amélioré pour la préparation de clopidogrel Ceased WO2007144729A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1018CH2006 2006-06-13
IN1018/CHE/2006 2006-06-13

Publications (1)

Publication Number Publication Date
WO2007144729A1 true WO2007144729A1 (fr) 2007-12-21

Family

ID=38831447

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2007/001542 Ceased WO2007144729A1 (fr) 2006-06-13 2007-06-08 Procédé amélioré pour la préparation de clopidogrel

Country Status (1)

Country Link
WO (1) WO2007144729A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011012961A1 (fr) * 2009-07-29 2011-02-03 Orchid Chemicals And Pharmaceuticals Ltd Procédé amélioré pour la préparation de bisulfate de clopidogrel
CN103308636A (zh) * 2013-04-28 2013-09-18 山东信立泰药业有限公司 一种D-(+)-α-(2-噻吩乙胺基)-α-(2-氯苯基)乙酸甲酯或其盐的质量控制方法及其在氯吡格雷生产中的应用
CN103483356A (zh) * 2013-09-30 2014-01-01 浙江美诺华药物化学有限公司 一种（s）-氯吡格雷的硫酸盐或盐酸盐的制备方法
CN112341475A (zh) * 2020-12-02 2021-02-09 烟台万润药业有限公司 一种硫酸氢氯吡格雷的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204469A (en) * 1990-07-10 1993-04-20 Sanofi Process for the preparation of an n-phenylacetic derivative of tetrahydrothieno(3,2-c)pyridine and its chemical intermediate
US20040260110A1 (en) * 1997-10-06 2004-12-23 Andre Bousquet Hydroxyacetic ester derivatives, preparation method and use as synthesis intermediates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5204469A (en) * 1990-07-10 1993-04-20 Sanofi Process for the preparation of an n-phenylacetic derivative of tetrahydrothieno(3,2-c)pyridine and its chemical intermediate
US20040260110A1 (en) * 1997-10-06 2004-12-23 Andre Bousquet Hydroxyacetic ester derivatives, preparation method and use as synthesis intermediates

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE CA [online] accession no. STN Database accession no. (146:441665) *
DATABASE CA [online] BALICKI R.: "Process for preparation of (+)-clopidogrel hydrogen sulphate", accession no. STN Database accession no. (146:274247) *
PRZEMYSL CHEMICZNY, vol. 85, no. 5, 2006, pages 342 - 343 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011012961A1 (fr) * 2009-07-29 2011-02-03 Orchid Chemicals And Pharmaceuticals Ltd Procédé amélioré pour la préparation de bisulfate de clopidogrel
CN103308636A (zh) * 2013-04-28 2013-09-18 山东信立泰药业有限公司 一种D-(+)-α-(2-噻吩乙胺基)-α-(2-氯苯基)乙酸甲酯或其盐的质量控制方法及其在氯吡格雷生产中的应用
CN103308636B (zh) * 2013-04-28 2014-04-09 山东信立泰药业有限公司 一种D-(+)-α-(2-噻吩乙胺基)-α-(2-氯苯基)乙酸甲酯或其盐的质量控制方法及其在氯吡格雷生产中的应用
CN103483356A (zh) * 2013-09-30 2014-01-01 浙江美诺华药物化学有限公司 一种（s）-氯吡格雷的硫酸盐或盐酸盐的制备方法
CN103483356B (zh) * 2013-09-30 2016-01-13 浙江美诺华药物化学有限公司 一种（s）-氯吡格雷的硫酸盐或盐酸盐的制备方法
CN112341475A (zh) * 2020-12-02 2021-02-09 烟台万润药业有限公司 一种硫酸氢氯吡格雷的制备方法
CN112341475B (zh) * 2020-12-02 2023-02-21 烟台万润药业有限公司 一种硫酸氢氯吡格雷的制备方法

Similar Documents

Publication Publication Date Title
IE912250A1 (en) Process for the preparation of an N-phenylacetic derivative of tetrahydrothieno [3,2-c] pyridine and its chemical intermediate
EA006198B1 (ru) Способ получения клопидогрела
US7629465B2 (en) Industrial process for preparation of Clopidogrel hydrogen sulphate
WO2009157011A1 (fr) Procédé de préparation de sunitinib de haute pureté et de ses sels pharmaceutiquement acceptables
WO2007144729A1 (fr) Procédé amélioré pour la préparation de clopidogrel
KR100553398B1 (ko) 티에노[3,2-ｃ]피리딘 유도체의 제조 방법 및 이에사용되는 중간체
US6495691B1 (en) Process for the preparation of tetrahydrothieno[3,2-c]pyridine derivatives
EP1501838B1 (fr) Procede de preparation de clopidogrel
EP1812435A2 (fr) Preparation d'intermediaires de tadalafil
KR20150056541A (ko) 시타글립틴 및 중간체 화합물의 제조 방법
JP2020517625A (ja) インドリノベンゾジアゼピン誘導体の調製方法
US20120232274A1 (en) Process for preparation of clopiodogrel bisulfate form-1
KR20130129902A (ko) 피라노-[2,3-c]피리딘 유도체를 제조하는 방법
EP1299389A1 (fr) Procede de preparation de derives de pyrazolopyrimidinone utiles pour traiter l'impuissance
AU2001258896A1 (en) A process for preparing pyrazolopyrimidinone derivatives for the treatment of impotence
CA2352520C (fr) Synthese de derives de tetrahydrothieno-[3,2-c]-pyridine
Jung et al. A Facile Solid‐Phase Synthesis of (+)‐(S)‐Clopidogrel
CZ300692B6 (cs) Zpusob prípravy solifenacinu
WO2011012961A1 (fr) Procédé amélioré pour la préparation de bisulfate de clopidogrel
WO2011074017A1 (fr) Nouveau procédé de préparation de palipéridone
CN114249674A (zh) 一种氯吡格雷中间体化合物
WO2009144263A2 (fr) Procédé d’obtention de 4-hydroxy-6-méthyl-5,6-dihydro-4h-thiéno [2,3-b] thiopyran-7,7-dioxyde et ses énantiomères, et ses applications
CA3095264A1 (fr) Procedes de synthese de 2-[(2s)-1-azabicyclo[2.2.2]oct-2-yl]-6- (3-methyl-1 h-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3h)-one
MX2008007340A (es) Proceso para la preparacion de s(+)-clopidogrel, mediante resolucion optica.
WO2007144895A1 (fr) Procédé de préparation du (s)-(+)-clopidogrel

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07766521

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 07766521

Country of ref document: EP

Kind code of ref document: A1