WO2011014611A2 - Préparation de l'olmésartan médoxomil - Google Patents

Préparation de l'olmésartan médoxomil Download PDF

Info

Publication number
WO2011014611A2
WO2011014611A2 PCT/US2010/043640 US2010043640W WO2011014611A2 WO 2011014611 A2 WO2011014611 A2 WO 2011014611A2 US 2010043640 W US2010043640 W US 2010043640W WO 2011014611 A2 WO2011014611 A2 WO 2011014611A2
Authority
WO
WIPO (PCT)
Prior art keywords
olmesartan medoxomil
formula
solvent comprises
water
trityl
Prior art date
Application number
PCT/US2010/043640
Other languages
English (en)
Other versions
WO2011014611A3 (fr
Inventor
Naveen Kumar Kolla
Nagaraju Manne
Anitha Naredla
Sachin Gulabrao Shinde
Original Assignee
Dr. Reddy's Laboratories Ltd.
Dr. Reddy's Laboratories, Inc.
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 Dr. Reddy's Laboratories Ltd., Dr. Reddy's Laboratories, Inc. filed Critical Dr. Reddy's Laboratories Ltd.
Publication of WO2011014611A2 publication Critical patent/WO2011014611A2/fr
Publication of WO2011014611A3 publication Critical patent/WO2011014611A3/fr

Links

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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to processes for preparing olmesartan medoxomil.
  • the present invention provides processes for preparing olmesartan medoxomil, without isolating one or more intermediate compounds.
  • the drug having the adopted name "olmesartan medoxomil” has a chemical name 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1 -[p- (o-1 H-tetrazol-5ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate, and is represented by structural Formula I.
  • Olmesartan is a selective angiotensin Il receptor antagonist
  • prodrug olmesartan medoxomil in products sold using the trademark BENICAR for oral administration as film-coated tablets containing 5 mg, 20 mg, or 40 mg of olmesartan medoxomil.
  • WO 2006/029056 discloses a process for the removal of a trityl group, involving the reaction of trityl olmesartan medoxomil with sulfuric acid, in a mixture of water and acetone, to obtain a solution of olmesartan medoxomil and a precipitate of the triphenylcarbinol salt.
  • the triphenylcarbinol precipitate is removed by filtration, followed by treating the solution with a base to precipitate olmesartan medoxomil.
  • aspects of the present application provide processes for the preparation of olmesartan medoxomil.
  • the present inventors have found that, after deprotection of the trityl group from trityl olmesartan medoxomil, as an alternative to removing the triphenyl carbinol salt, it can be dissolved in a suitable solvent during workup and then olmesartan medoxomil can be isolated. This provides advantages of cost and ease of conducting the synthesis.
  • An aspect of the present invention provides a one-pot process for the preparation of olmesartan medoxomil, proceeding without isolation of intermediate compounds formed in various stages of the process, and also not involving filtration of the formed triphenylcarbinol salt after completion of a deprotection reaction.
  • the present invention provides processes for the preparation of olmesartan medoxomil, which can be practiced on an industrial scale and provide high yields of the product.
  • the present application provides processes for preparing olmesartan medoxomil, embodiments comprising:
  • Formula III Formula IV b) reacting the compound of Formula IV with a base to form trityl olmesartan;
  • steps b), c), and d) deprotecting trityl olmesartan medoxomil to form olmesartan medoxomil.
  • steps b), c), and d) are carried out without isolating the intermediate compounds formed in the immediately preceding step, followed by isolation of trityl olmesartan medoxomil.
  • the present invention provides processes for the preparation of olmesartan medoxomil, starting from trityl olmesartan medoxomil, without precipitating a triphenylcarbinol salt.
  • the present invention provides processes for preparing olmesartan medoxomil, comprising deprotecting trityl olmesartan medoxomil in the presence of an acid, without precipitating a triphenylcarbinol salt.
  • the present invention provides pharmaceutical compositions comprising olmesartan medoxomil prepared according to a process of the present invention, together with one or more pharmaceutically acceptable excipients.
  • one or more sequential steps are carried out without isolating the intermediate compounds that are formed.
  • one or more of steps b), c), and d) are carried out without isolating the intermediate compounds formed in the immediately preceding step, followed by isolation of trityl olmesartan medoxomil.
  • Step a) involves reacting alkyl-4-(1 -hydroxy-1-methylethyl)-2- propylimidazole-5-carboxy-late of Formula Il with N-(triphenylmethyl)-5-[4'- (bromomethyl)biphenyl-2-yl]tetrazole of Formula III, in the presence of a base and nonpolar solvent, to obtain alkyl 4-(1 -hydroxy-1-methylethyl)-2-propyl-1 -[[2'-[2- (thphenylmethyl)-2H-tetrazol-5yl]biphenyl-4-yl]methyl]imidazole-5-carboxylate of Formula IV.
  • Non-polar solvents that can be used in step a) include, but are not limited to, hydrocarbons such as hexane, heptane, cyclohexane, methylcyclohexane, toluene, xylene, and any mixtures thereof.
  • the reaction may be carried out with a mixture of a non-polar solvent and water.
  • the content of water can range from about 1 to about 90% by weight of the non-polar solvent.
  • Suitable bases that can be used for the reaction include, but are not limited to, organic bases such as diisopropylamine and tertiary-butylamine, and inorganic bases such as alkali metal hydroxides, alkali metal alkoxides, and alkali metal carbonates.
  • the alkali metal hydroxides include lithium hydroxide, sodium hydroxide, and potassium hydroxide
  • alkali metal alkoxides include sodium methoxide, sodium ethoxide, and potassium tertiary-butoxide
  • alkali metal carbonates include sodium carbonate and potassium carbonate.
  • aqueous solutions of a base containing about 5% to 50%, or about 10% to 20%, (w/v) of the base can be used.
  • phase transfer catalysts that can be used include, but are not limited to, tetralkylammonium or phosphonium salts, such as tetrabutylammonium bromide, tetrabutylammonium fluoride, and tetrabutylammonium hydrogen sulphate, crown ethers such as 15-crown-5 and 18-crown-6, and the like.
  • Suitable temperatures for conducting the reaction range from about 25°C to the reflux temperature of the solvent or mixture of solvents used.
  • the compound of Formula IV obtained as a product can be isolated, or the reaction mixture can be directly progressed to the next stage to form trityl olmesartan.
  • Step b) involves reacting the compound of Formula IV with a base to give trityl olmesartan.
  • Suitable bases include, but are not limited to, organic bases such as diisopropylamine and tertiary-butylamine, and inorganic bases such as alkali metal hydroxides, alkali metal alkoxides, and alkali metal carbonates.
  • the alkali metal hydroxides include lithium hydroxide, sodium hydroxide, and potassium hydroxide
  • alkali metal alkoxides include sodium methoxide, sodium ethoxide, and potassium tertiary-butoxide
  • alkali metal carbonates include sodium carbonate and potassium carbonate.
  • an additional solvent may be added to the reaction mixture.
  • the added solvent may or may not be the same solvent that is used for the reaction in step a).
  • water may be added to the reaction mixture.
  • the reaction may be carried out at temperatures ranging from about 25°C to the reflux temperature of the solvent or mixture of solvents used.
  • step b) The product obtained in step b) may be optionally isolated, or the reaction mixture may be progressed directly to step c).
  • Step c) involves reacting trityl olmesartan with 5-methyl-2-oxo-(1 ,3- dioxolene-4-yl)methyl chloride to give trityl olmesartan medoxomil.
  • the reaction is suitably conducted in the presence of a base.
  • the base may be directly added to the reaction mixture obtained from step b) when the reaction is conducted without isolation of the product obtained in step b).
  • the base may be any of inorganic bases such as alkali metal hydroxides, alkali metal alkoxides, and alkali metal carbonates.
  • the alkali metal hydroxides include lithium hydroxide, sodium hydroxide, and potassium hydroxide
  • alkali metal alkoxides include sodium methoxide, sodium ethoxide, and potassium tertiary-butoxide
  • alkali metal carbonates include sodium carbonate and potassium carbonate.
  • Organic bases may also be used, such as diisopropylamine and tertiary- butylamine.
  • reaction may be carried out in the presence of a phase transfer catalyst such as a tetralkylammonium or phosphonium salt, such as tetrabutylammonium bromide, tetrabutylammonium fluoride, and
  • a phase transfer catalyst such as a tetralkylammonium or phosphonium salt, such as tetrabutylammonium bromide, tetrabutylammonium fluoride, and
  • the reaction may be carried out at temperatures ranging from about 25°C to the reflux temperature of the solvent or mixture of solvents used.
  • step c) The product obtained in step c) may be progressed to a deprotection reaction without isolation of the trityl olmesartan medoxomil obtained.
  • the isolation may be accomplished using techniques known in the art, for example, by neutralization using an acid.
  • the trityl olmesartan medoxomil obtained can be further purified by recrystallization or slurrying in a suitable solvent.
  • Suitable organic solvents which can be used for recrystallization or slurrying include, but are not limited to: ketones such as acetone, ethyl methyl ketone, and butanone; nitriles such as acetonitrile and propionitrile; alcohols such as methanol, ethanol, isopropanol, 1 -butyl alcohol, 2-butyl alcohol, and tertiary- butyl alcohol; hydrocarbons such as hexane, heptane, cyclohexane, benzene, xylene, and toluene; halogenated hydrocarbons such as dichloromethane, chloroform, and ethylene dichloride; esters such as ethyl acetate and propyl acetate; and any mixtures thereof in various proportions without limitation.
  • ketones such as acetone, ethyl methyl ketone, and butanone
  • nitriles such as acetonitrile
  • Step d) involves deprotecting trityl olmesartan medoxomil to give
  • the deprotection reaction is carried out by treating the protected compound with an acid.
  • Suitable acids include, but are not limited to, sulfuric acid, acetic acid, hydrochloric acid, nitric acid, phosphoric acid, and the like.
  • Suitable solvents include, but are not limited to: alcohols such as methanol, ethanol, isopropanol, 1 -butyl alcohol, 2-butyl alcohol, and tertiary-butyl alcohol; hydrocarbons such as hexane, heptane, cyclohexane, benzene, xylene, and toluene; halogenated hydrocarbons such as dichloromethane, chloroform, and ethylene dichloride; esters such as ethyl acetate and propyl acetate; and any mixtures thereof in various proportions without limitation.
  • alcohols such as methanol, ethanol, isopropanol, 1 -butyl alcohol, 2-butyl alcohol, and tertiary-butyl alcohol
  • hydrocarbons such as hexane, heptane, cyclohexane, benzene, xylene, and toluene
  • halogenated hydrocarbons such
  • the present invention provides processes for preparing olmesartan medoxomil, starting from trityl olmesartan medoxomil, without isolating a thphenylcarbinol salt.
  • the deprotection reaction is first carried out in a water-miscible solvent such as: alcohols, including methanol, ethanol, isopropyl alcohol, and n-butanol; ketones, including acetone and methyl ethyl ketone; and nitriles, including acetonitrile and propionithle; and, after completion of the reaction, a water- immiscible solvent may be added.
  • a water-miscible solvent such as: alcohols, including methanol, ethanol, isopropyl alcohol, and n-butanol
  • ketones including acetone and methyl ethyl ketone
  • nitriles including acetonitrile and propionithle
  • Water-immiscible solvents that can be used include, but are not limited to: hydrocarbons such as hexane, heptane, cyclohexane, benzene, xylene, and toluene; esters such as ethyl acetate, isopropyl acetate, isobutyl acetate, and tertiary-butyl acetate; and halogenated hydrocarbons such as dichloromethane and chloroform.
  • hydrocarbons such as hexane, heptane, cyclohexane, benzene, xylene, and toluene
  • esters such as ethyl acetate, isopropyl acetate, isobutyl acetate, and tertiary-butyl acetate
  • halogenated hydrocarbons such as dichloromethane and chloroform.
  • the water-immiscible solvent is chosen such that the
  • triphenylcarbinol salt is highly soluble in the solvent, so that after completion of the reaction, the triphenylcarbinol salt remains dissolved in the water-immiscible solvent layer and the product remains in the aqueous layer.
  • the aqueous layer may be subjected to further treatment, such as treatment with a base for extraction of olmesartan medoxomil.
  • the water-miscible solvent used is an alcohol and the water-immiscible solvent used is a hydrocarbon.
  • the product may be extracted from the aqueous layer by treatment with a base.
  • Suitable bases that can be used for basic hydrolysis include, but are not limited to: alkoxides, including sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium tertiary-butoxide, potassium tertiary- butoxide, sodium secondary-butoxide, potassium secondary-butoxide, and the like; alkali metal hydroxides, including sodium hydroxide, potassium hydroxide, and lithium hydroxide; alkali metal carbonates, including sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, lithium carbonate, and the like; and alkali metal hydrides, including sodium hydride and the like.
  • Olmesartan medoxomil that is obtained can be purified by recrystallization or slurrying in a suitable solvent.
  • Suitable organic solvents that can be used for recrystallization or slurry formation include, but are not limited to: esters such as ethyl acetate, n-butyl acetate, tertiary-butyl acetate, isopropyl acetate, and the like; ketones such as acetone, ethyl methyl ketone, and the like; hydrocarbons such as toluene, xylene, n-hexane, n-heptane, cyclohexane, and the like; nitriles such as acetonitrile, propionithle, and the like; and any mixtures thereof in various proportions.
  • esters such as ethyl acetate, n-butyl acetate, tertiary-butyl acetate, isopropyl acetate, and the like
  • ketones such as acetone, ethyl methyl ketone, and the like
  • Olmesartan medoxomil obtained using a process of the present invention has a purity about 99.5% or higher, or about 99.9% or higher, by weight, as determined using high performance liquid chromatography (HPLC).
  • HPLC high performance liquid chromatography
  • the present invention provides pharmaceutical compositions comprising olmesartan medoxomil, prepared according to a process of the present invention, together with one or more pharmaceutically acceptable excipients.
  • compositions comprising olmesartan medoxomil, together with one or more pharmaceutically acceptable carriers, may be
  • Formulations may be in the form of immediate release, delayed release, or modified release.
  • immediate release compositions may be conventional, dispersible, chewable, mouth dissolving, or flash melt preparations, and modified release compositions that may comprise hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic, release rate-controlling
  • compositions may be prepared using any of techniques such as direct blending, dry granulation, wet granulation, or extrusion and spheronization.
  • Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated, or modified release coated.
  • phosphate tricalcium phosphate
  • mannitol sorbitol
  • sugar and the like binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones,
  • hydroxypropyl celluloses hydroxypropyl methylcelluloses, pregelatinized starches, and the like
  • disintegrants such as starches, sodium starch glycolate,
  • pregelatinized starches crospovidones, croscarmellose sodium, colloidal silicon dioxide, and the like
  • lubricants such as stearic acid, magnesium stearate, zinc stearate, and the like
  • glidants such as colloidal silicon dioxide and the like
  • solubility or wetting enhancers such as anionic, cationic, or neutral surfactants
  • complex forming agents such as various grades of cyclodexthns and resins
  • release rate-controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethyl celluloses, methyl celluloses, various grades of methyl methacrylates, waxes, and the like.
  • pharmaceutically acceptable excipients that can be used include, but are not limited to, film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants and the like.
  • olmesartan medoxomil is a useful active ingredient in the range of 20 mg to 350 mg, or 40 mg to 320 mg, per unit dose.
  • the mass is cooled to 25-35°C, water (50 mL) is added, and the pH is adjusted to about 6-7 by adding 10% aqueous HCI.
  • the layers are separated.
  • the aqueous layer is extracted with toluene (25 mL).
  • the organic layers are combined and washed with water (25 mL).
  • the solvent is distilled under reduced pressure.
  • Methanol (25 mL) is added to the residue.
  • the mixture is cooled to 0-5 0 C and stirred at that temperature for 45 minutes.
  • the formed solid is filtered, washed with methanol (10 mL) and dried for 45 minutes under vacuum (yield 3.0 g).
  • EXAMPLE 3 PREPARATION OF TRITYL OLMESARTAN MEDOXOMIL.
  • Toluene (180 L) is placed into a reactor and water (3.17 L) is added, followed by addition of ethyl-4-(1 -hydroxy-1 -methylethyl)-2-propylimidazole-5- carboxylate (18.0 Kg).
  • the mass is stirred for about 10 minutes, heated to about 45°C, and potassium carbonate (25.85 Kg) is added.
  • the temperature of the mass is raised to about 65°C and maintained for about 45 minutes.
  • N-(triphenylmethyl)- 5-[4'-(bromomethyl)biphenyl-2-yl]tetrazole (48.9 Kg) and tetrabutylammonium bromide (4.82 Kg) are added at the same temperature and the mixture is stirred at 60-70 0 C for 10 hours. Reaction completion is verified using thin layer
  • TLC chromatography
  • the mass is stirred at about 55°C for about 11 hours. After the reaction is complete, the mass is cooled to about 20°C, water (540 L) is added and the pH is adjusted to about 6-7 by adding 10% aqueous HCI. The layers are separated. The aqueous layer is extracted with toluene (240 L). The organic layers are combined and washed with water (270 L). The solvent is distilled under reduced pressure. Acetone (189 L) is added to the residue and the mixture is heated to about 45°C to produce a solution, then the solution is cooled to about 30 0 C and maintained for about 20 minutes, followed by cooling to about 2°C and maintaining for about 3 hours. The formed solid is filtered, washed with acetone (54 L), and dried for about 4 hours. The material obtained is re- crystallized from acetonitrile to yield 34.0 Kg of the title compound.
  • EXAMPLE 4 PREPARATION OF OLMESARTAN MEDOXOMIL FROM TRITYL OLMESARTAN MEDOXOMIL.
  • Acetone (46 L) and trityl olmesartan medoxomil (23 Kg) are mixed, heated to 55°C, and maintained for about 20 minutes. The mass is cooled to about 25°C, then further cooled to about 5°C and maintained for about 60 minutes. The solid is filtered and washed with acetone (23 L). The wet solid is dried at about 45°C for about 4 hours. The dry solid and methanol (108.5 L) are stirred at about 25°C for 10 minutes. Aqueous HCI (3.25 Kg) is added and the mixture is stirred at about 25°C for 3 hours. Hexane (104 L) and water (207 L) are added and stirred at about 25°C for 15 minutes.
  • the layers are separated and the aqueous layer is washed with hexane (124 L).
  • Dichloromethane (166 L) is added to the aqueous layer and the pH is adjusted to about 3-4 by adding aqueous NaHCO 3 solution (10%, 3.0 Kg).
  • the layers are separated and the aqueous layer is extracted with dichloromethane (164 L).
  • the dichloromethane layers are combined and washed with water (104 L).
  • the solvent is distilled under reduced pressure.
  • Acetone (217 L) is added to the residue and the mixture is stirred at about 55°C for 30 minutes. About 80% of the solvent is distilled under reduced pressure.
  • the concentrate is cooled to 25-35°C.
  • the precipitated solid is filtered and dried under vacuum at 50 0 C, to yield 8.4 Kg of the title compound.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne des procédés de préparation de l'olmésartan médoxomil. Dans les modes de réalisation, les procédés de préparation de l'olmésartan médoxomil ne nécessitent pas d'isoler un ou plusieurs composés intermédiaires.
PCT/US2010/043640 2009-07-30 2010-07-29 Préparation de l'olmésartan médoxomil WO2011014611A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN1810CH2009 2009-07-30
IN1810/CHE/2009 2009-07-30
US29336110P 2010-01-08 2010-01-08
US61/293,361 2010-01-08

Publications (2)

Publication Number Publication Date
WO2011014611A2 true WO2011014611A2 (fr) 2011-02-03
WO2011014611A3 WO2011014611A3 (fr) 2011-07-21

Family

ID=43529930

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/043640 WO2011014611A2 (fr) 2009-07-30 2010-07-29 Préparation de l'olmésartan médoxomil

Country Status (1)

Country Link
WO (1) WO2011014611A2 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013021312A1 (fr) * 2011-08-05 2013-02-14 Lupin Limited Procédé de préparation d'olmésartan médoxomil
US8735598B2 (en) 2008-06-09 2014-05-27 Daiichi Sankyo Company, Limited Method for producing 1-biphenylmethylimidazole compound
US8859600B2 (en) 2009-04-28 2014-10-14 Daiichi Sankyo Company, Limited Acetone solvate crystals of trityl olmesartan medoxomil
US8933241B2 (en) 2009-04-28 2015-01-13 Daiichi Sankyo Company, Limited Method for producing olmesartan medoxomil
CN105418593A (zh) * 2015-11-25 2016-03-23 蚌埠丰原涂山制药有限公司 一种奥美沙坦酯关键中间体及奥美沙坦酯的制备方法
CN105481842A (zh) * 2015-12-15 2016-04-13 江苏中邦制药有限公司 一种奥美沙坦酯的制备方法
CN105906614A (zh) * 2016-05-12 2016-08-31 山东罗欣药业集团股份有限公司 一种奥美沙坦酯的制备方法
US10119444B2 (en) 2012-02-21 2018-11-06 Achates Power, Inc. Exhaust management strategies for opposed-piston, two-stroke engines
CN110452228A (zh) * 2019-09-05 2019-11-15 黄冈鲁班药业股份有限公司 高纯度三苯基奥美沙坦乙酯的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060069141A1 (en) * 2004-09-02 2006-03-30 Lilach Hedvati Preparation of olmesartan medoxomil
US20060258727A1 (en) * 2005-01-03 2006-11-16 Lilach Hedvati Olmesartan medoxomil with reduced levels of impurities
US20090131680A1 (en) * 2005-07-29 2009-05-21 Krka Process for the preparation of olmesartan medoxomil

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060069141A1 (en) * 2004-09-02 2006-03-30 Lilach Hedvati Preparation of olmesartan medoxomil
US20060258727A1 (en) * 2005-01-03 2006-11-16 Lilach Hedvati Olmesartan medoxomil with reduced levels of impurities
US20090131680A1 (en) * 2005-07-29 2009-05-21 Krka Process for the preparation of olmesartan medoxomil

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8735598B2 (en) 2008-06-09 2014-05-27 Daiichi Sankyo Company, Limited Method for producing 1-biphenylmethylimidazole compound
US8859600B2 (en) 2009-04-28 2014-10-14 Daiichi Sankyo Company, Limited Acetone solvate crystals of trityl olmesartan medoxomil
US8933241B2 (en) 2009-04-28 2015-01-13 Daiichi Sankyo Company, Limited Method for producing olmesartan medoxomil
WO2013021312A1 (fr) * 2011-08-05 2013-02-14 Lupin Limited Procédé de préparation d'olmésartan médoxomil
US8981110B2 (en) 2011-08-05 2015-03-17 Lupin Limited Process for the preparation of olmesartan medoxomil
US10119444B2 (en) 2012-02-21 2018-11-06 Achates Power, Inc. Exhaust management strategies for opposed-piston, two-stroke engines
CN105418593A (zh) * 2015-11-25 2016-03-23 蚌埠丰原涂山制药有限公司 一种奥美沙坦酯关键中间体及奥美沙坦酯的制备方法
CN105481842A (zh) * 2015-12-15 2016-04-13 江苏中邦制药有限公司 一种奥美沙坦酯的制备方法
CN105906614A (zh) * 2016-05-12 2016-08-31 山东罗欣药业集团股份有限公司 一种奥美沙坦酯的制备方法
CN110452228A (zh) * 2019-09-05 2019-11-15 黄冈鲁班药业股份有限公司 高纯度三苯基奥美沙坦乙酯的制备方法

Also Published As

Publication number Publication date
WO2011014611A3 (fr) 2011-07-21

Similar Documents

Publication Publication Date Title
WO2011014611A2 (fr) Préparation de l'olmésartan médoxomil
EP1831186B1 (fr) Procédé de prépartion de valsartan
US8592474B2 (en) Process for the preparation or purification of olmesartan medoxomil
WO2006029057A1 (fr) Epuration d'olmesartan medoxomil
CA2581723A1 (fr) Methode de preparation de telmisartan
CZ288629B6 (cs) Forma B 2-n-butyl-3-[[2´-(tetrazol-5-yl)bifenyl-4-yl]-1,3-diazaspiro[4.4]non-1-en-onu, způsoby její přípravy a farmaceutická kompozice tuto formu B obsahující
CZ299902B6 (cs) Zpusob odstranování trifenylmethanové chránicí skupiny u prekurzoru antihypertenzních léciv
WO2011007368A2 (fr) Procédé amélioré de préparation d'olmésartan
WO2004094391A2 (fr) Procede de preparation du valsartan et de ses intermediaires
US20060287537A1 (en) Method of removing the triphenylmethane protecting group
US7041832B2 (en) Processes for preparing losartan and losartan potassium
US20050059827A1 (en) Process for the preparation of valsartan and intermediates thereof
US20080214637A1 (en) Process for the Synthesis of Tetrazoles
JP2004520446A5 (fr)
SK286740B6 (sk) Spôsob syntézy draselnej soli losartanu
EP1622882B1 (fr) Procede de preparation de n -(1-oxopentyl)- n- ¬¬2'-(1h -tetrazol-5-y1) 1,1'-biphenyl|-4-y1|methyl|-l-valine (valsartan)
EP3498698A1 (fr) Formes solides de valsartan disodium et son procédé de préparation
EP1634880A2 (fr) Procédé pour la fabrication de losartan et losartan sous forme de sel de potasse
KR101266224B1 (ko) 트리틸 올메사르탄 메독소밀의 개선된 제조방법
CZ298329B6 (cs) Zpusob výroby 1-(cyklohexyloxykarbonyloxy)ethyl-2-ethoxy-1-[[2´-(1H-tetrazol-5-yl)bifenyl-4-yl]methyl]benzimidazol-7-karboxylátu (candesartan cilexetilu)
CZ20032319A3 (cs) Způsob odstraňování trifenylmethanové chránící skupiny z 1-trityl-5-(4'-subst. aminomethyl-1,1' -bifenyl-2-yl)-1H-tetrazolů a způsob výroby draselné soli losartanu, irbesartanu a valsartanu s jeho použitím
Young &Co EUROPEAN PATENT SPECIFICATION
CZ302240B6 (cs) Zpusob odstranování trifenylmethanové chránicí skupiny u prekursoru antihypertensiv majících labilní, metabolicky odbouratelnou skupinu
SI21964A (sl) Priprava tetrazolskega derivata

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: 10805022

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 430/CHENP/2012

Country of ref document: IN

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10805022

Country of ref document: EP

Kind code of ref document: A2