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WO2012069025A1 - (5-méthyl-2-oxo-1,3-dioxol-4-ylméthyl)-4-(1-hydroxy-1-méthyl-propyl)-2- propyl-1-[2'-(1h-tétrazol-5-yl)biphényl-4-yl-méthyl]imidazole-5- carboxylate en tant qu'impureté de l'olmésartan médoxomil et son procédé de préparation - Google Patents

(5-méthyl-2-oxo-1,3-dioxol-4-ylméthyl)-4-(1-hydroxy-1-méthyl-propyl)-2- propyl-1-[2'-(1h-tétrazol-5-yl)biphényl-4-yl-méthyl]imidazole-5- carboxylate en tant qu'impureté de l'olmésartan médoxomil et son procédé de préparation Download PDF

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Publication number
WO2012069025A1
WO2012069025A1 PCT/CZ2011/000112 CZ2011000112W WO2012069025A1 WO 2012069025 A1 WO2012069025 A1 WO 2012069025A1 CZ 2011000112 W CZ2011000112 W CZ 2011000112W WO 2012069025 A1 WO2012069025 A1 WO 2012069025A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
methyl
propyl
compound
hydroxy
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/CZ2011/000112
Other languages
English (en)
Inventor
Jan Stach
Lukas Placek
Radim Krulis
Stanislav Radl
Josef Cerny
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.)
Zentiva KS
Original Assignee
Zentiva KS
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 Zentiva KS filed Critical Zentiva KS
Publication of WO2012069025A1 publication Critical patent/WO2012069025A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/10—Heterocyclic 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 linked by a carbon chain containing aromatic rings

Definitions

  • the invention relates to the compound of formula VI
  • Olmesartan medoxomil belongs to the drug group called angiotensin II antagonists, which helps to control high blood pressure.
  • Angiotensin II antagonists are used as drugs for the cardiovascular system, especially to control high blood pressure.
  • This group comprises important drugs such as losartan (Cozaar ® ), irbesartan (Avapro ® ), or valsartan (Diovan ® ).
  • olmesartan medoxomil of formula I is a prodrug that releases the actual effective compound, olmesartan of formula II, in the organism. Due to better bio availability of the prodrug higher levels of olmesartan are achieved than in the case of its direct administration.
  • the present invention provides (5-methyl-2-oxo- 1 ,3-dioxol-4-ylmethyl)-4-(l -hydroxy- 1 - methyl-propyl)-2-propyl-l-[2 ' -(lH-tetrazol-5-yl)biphenyl-4-yl-methyl]imidazole-5- carboxylate of formula VI (hereinafter also referred to as Me-OM) and a method of its preparation.
  • the invention also provides the intermediates of formulae VII, 5 and 6 for the preparation of the compound of formula VI, a method for the determination of the compound of formula VI in olmesartan medoxomil, and, further, use of the intermediates of synthesis of the compound of formula VI as standards of impurities in the analysis of intermediates of olmesartan medoxomil production.
  • a method for the determination of the compound of formula VI in olmesartan medoxomil a method for the determination of the compound of formula VI in olmesartan medoxomil
  • use of the intermediates of synthesis of the compound of formula VI as standards of impurities in the analysis of intermediates of olmesartan medoxomil production.
  • the invention provides (5-methyl-2-oxo-l ,3-dioxol-4-ylmethyl)-4-(l-hydroxy-l-methylpro- pyl)-2-propyl-l-[2 ' -(lH-tetrazol-5-yl)biphenyl-4-yl-methyl]imidazole-5-carboxylate of formula VI (Me-OM), which the authors have managed to identify, by a combination of HPLC and mass spectroscopy, as an admixture to olmesartan medoxomil of formula I prepared in accordance with US 5 616 599, and then to prepare in the pure form allowing practical application.
  • the impurity of formula VII is quite difficult to remove by crystallization of the intermediate 1 and in the further synthetic stages the homologous impurities 5 and 6, which are formed from the precursor of formula VII, are similarly difficult to remove from the corresponding olmesartan medoxomil synthesis intermediates of formulae 2 and 3.
  • the impurity of formula VI has been prepared in accordance with Scheme 3 and characterized by means of high resolution mass spectroscopy (HR-MS) and nuclear magnetic resonance (NMR).
  • the corresponding precursors of the impurity of formula VI have also been identified in the intermediates of olmesartan medoxomil synthesis of formulae 1, 2 and 3.
  • the compounds of formulae VI, VII, 5 and 6 are industrially applicable as standards or reference substances for the development and set-up of analytic methods suitable for analysis of olmesartan medoxomil destined for pharmaceutical purposes, or for analysis of intermediates of its production, especially for the purposes of quality control during production of olmesartan medoxomil destined for pharmaceutical use, or quality assurance of olmesartan medoxomil as the input raw material for the production of pharmaceutical preparations.
  • Preparations of the above mentioned compounds with the weight content of at least 10%, preferably with the content of at least 50%, most preferably with the content of at least 90%, related to the total weight of the sample, can be used as reference materials.
  • the most preferable method of ensuring compliance with the limit of 0.15% by weight for the content of impurity VI in olmesartan medoxomil then consists in using a Grignard reagent (which can generally be any methyl magnesium halide MeMgX, wherein X stands for CI, Br or I, similarly as in synthesis of compound VI), containing at most 0.15% by weight of the corresponding ethyl homologue.
  • a Grignard reagent which can generally be any methyl magnesium halide MeMgX, wherein X stands for CI, Br or I, similarly as in synthesis of compound VI

Landscapes

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

Abstract

La présente invention concerne le composé de formule VI et son procédé de préparation, ainsi que des intermédiaires de sa préparation. L'invention concerne également l'utilisation de ces intermédiaires en tant qu'étalons dans l'analyse de l'olmésartan médoxomil antagoniste de l'angiotensine II de formule I et de ses intermédiaires de production.
PCT/CZ2011/000112 2010-11-24 2011-11-23 (5-méthyl-2-oxo-1,3-dioxol-4-ylméthyl)-4-(1-hydroxy-1-méthyl-propyl)-2- propyl-1-[2'-(1h-tétrazol-5-yl)biphényl-4-yl-méthyl]imidazole-5- carboxylate en tant qu'impureté de l'olmésartan médoxomil et son procédé de préparation Ceased WO2012069025A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ2010-863A CZ305129B6 (cs) 2010-11-24 2010-11-24 (5-Methyl-2-oxo-1,3-dioxol-4-ylmethyl)-4-(1-hydroxy-1-methyl-propyl)-2-propyl-1-[2´-(1H-tetrazol-5-yl)bifenyl-4-yl-methyl]imidazol-5-karboxylát jako nečistota olmesartan medoxomilu a způsob jeho přípravy
CZPV2010-863 2010-11-24

Publications (1)

Publication Number Publication Date
WO2012069025A1 true WO2012069025A1 (fr) 2012-05-31

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2011/000112 Ceased WO2012069025A1 (fr) 2010-11-24 2011-11-23 (5-méthyl-2-oxo-1,3-dioxol-4-ylméthyl)-4-(1-hydroxy-1-méthyl-propyl)-2- propyl-1-[2'-(1h-tétrazol-5-yl)biphényl-4-yl-méthyl]imidazole-5- carboxylate en tant qu'impureté de l'olmésartan médoxomil et son procédé de préparation

Country Status (2)

Country Link
CZ (1) CZ305129B6 (fr)
WO (1) WO2012069025A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105158359A (zh) * 2015-08-19 2015-12-16 江苏中邦制药有限公司 一种奥美沙坦酯及其中间体的高效液相色谱分离分析方法
CN111044622A (zh) * 2018-10-12 2020-04-21 珠海润都制药股份有限公司 一种沙库比曲缬沙坦钠中缬沙坦有关物质a的检测方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616599A (en) 1991-02-21 1997-04-01 Sankyo Company, Limited Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their therapeutic use
WO2006073519A1 (fr) 2005-01-03 2006-07-13 Teva Pharmaceutical Industries Ltd. Olmesartan medoxomil a teneur reduite en impuretes

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA201171413A1 (ru) * 2009-05-20 2012-09-28 Ранбакси Лабораториз Лимитед Способ получения олмесартана медоксомила
WO2011021224A2 (fr) * 2009-08-19 2011-02-24 Msn Laboratories Limited Procédé de préparation de (5-méthyl-2-oxo- 1,3-dioxolen-4-yl)méthyl-4-(1-hydroxy- 1 -méthyléthyl)-2-propyl- l-[4-[2-(tétrazol-5-yl)phényl]phényl]méthyl imidazole-5-carboxylate

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5616599A (en) 1991-02-21 1997-04-01 Sankyo Company, Limited Angiotensin II antagosist 1-biphenylmethylimidazole compounds and their therapeutic use
WO2006073519A1 (fr) 2005-01-03 2006-07-13 Teva Pharmaceutical Industries Ltd. Olmesartan medoxomil a teneur reduite en impuretes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YANAGISAWA H ET AL: "Nonpeptide Angiotensin II Antagonists. Synthesis, Biological Activities, and Structure-Activity Relationships of Imidazole-5-Carboxylic Acids Bearing Alkyl, Alkenyl and Hydroxyalkyl Substitutents at the 4-Position and Their Related Compounds", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 39, no. 1, 5 January 1996 (1996-01-05), pages 323 - 338, XP002144317, ISSN: 0022-2623, DOI: 10.1021/JM950450F *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105158359A (zh) * 2015-08-19 2015-12-16 江苏中邦制药有限公司 一种奥美沙坦酯及其中间体的高效液相色谱分离分析方法
CN111044622A (zh) * 2018-10-12 2020-04-21 珠海润都制药股份有限公司 一种沙库比曲缬沙坦钠中缬沙坦有关物质a的检测方法

Also Published As

Publication number Publication date
CZ305129B6 (cs) 2015-05-13
CZ2010863A3 (cs) 2012-06-06

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