WO2009123483A1 - Process for preparation of telmisartan - Google Patents

Process for preparation of telmisartan Download PDF

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Publication number
WO2009123483A1
WO2009123483A1 PCT/PL2009/000027 PL2009000027W WO2009123483A1 WO 2009123483 A1 WO2009123483 A1 WO 2009123483A1 PL 2009000027 W PL2009000027 W PL 2009000027W WO 2009123483 A1 WO2009123483 A1 WO 2009123483A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
methyl
process according
iv
Prior art date
Application number
PCT/PL2009/000027
Other languages
French (fr)
Inventor
Mariusz Marek Gruza
Joanna Zagrodzka
Piotr Krzeczynski
Katarzyna Filip
Original Assignee
Zaklady Farmaceutyczne Polpharma Sa
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
Priority to PL384830 priority Critical
Priority to PL38483008 priority
Application filed by Zaklady Farmaceutyczne Polpharma Sa filed Critical Zaklady Farmaceutyczne Polpharma Sa
Publication of WO2009123483A1 publication Critical patent/WO2009123483A1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08Radicals containing only hydrogen and carbon atoms
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of products other than chlorine, adipic acid, caprolactam, or chlorodifluoromethane, e.g. bulk or fine chemicals or pharmaceuticals
    • Y02P20/55Synthetic design, e.g. reducing the use of auxiliary or protecting groups

Abstract

A process for preparation of telmisartan comprises: (i) oxidation of compound of formula (a), wherein R2 is a hydrogen atom or a substituent of formula (b), in which R1 is a protecting group for the carboxyl function, to an aldehyde of formula (c), in which R2 is defined as in the formula (a), and, optionally, (ii) in case R2 in the compound (c) thus obtained is a hydrogen atom, iV-alkylation of the compound (c) with a biphenyl derivative, (iii) treatment of the compound (c) thus obtained with N- methyl- o-nitroaniline in a cyclocondensation reaction, and (iv) cleavage of the protecting group R1.

Description

PROCESS FOR PREPARATION OF TELMISARTAN

Field of the invention

The present invention relates to a process for the preparation of telmisartan.

Telmisartan, 4'-[(l,4'-dimethyl-2'-propyl-[2,6'-bis-lH-benzim- idazol]-r-yl)methyl]-[l, l'-biphenyl]-2-carboxylic acid, is non- peptide ATi -subtype specific angiotensin II antagonist, indicated for the treatment of hypertension, either alone or in combination with other antihypertensive agents.

Background of the invention The prior art general method of the synthesis of telmisartan,<