WO2012104863A2 - Procédé pour contrôler la teneur d'un énantiomère d'oméprazole - Google Patents

Procédé pour contrôler la teneur d'un énantiomère d'oméprazole Download PDF

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Publication number
WO2012104863A2
WO2012104863A2 PCT/IN2011/000840 IN2011000840W WO2012104863A2 WO 2012104863 A2 WO2012104863 A2 WO 2012104863A2 IN 2011000840 W IN2011000840 W IN 2011000840W WO 2012104863 A2 WO2012104863 A2 WO 2012104863A2
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WO
WIPO (PCT)
Prior art keywords
omeprazole
cyclic amine
toluene
methylene chloride
binol
Prior art date
Application number
PCT/IN2011/000840
Other languages
English (en)
Other versions
WO2012104863A3 (fr
Inventor
Bandi Parthasaradhi Reddy
Kura Rathnakar Reddy
Dasari Muralidhara Reddy
Rapolu Raji Reddy
Bandi Vamsi Krishna
Original Assignee
Hetero Research Foundation
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 Hetero Research Foundation filed Critical Hetero Research Foundation
Publication of WO2012104863A2 publication Critical patent/WO2012104863A2/fr
Publication of WO2012104863A3 publication Critical patent/WO2012104863A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to process for controlling the content of single enantiomer of omeprazole with respect to other enantiomers.
  • Omeprazole chemically 5-methoxy-2-[[(4-methoxy-3,5-dirnethyl-2- pyridinyl)methyl]sulfinyl]-lH-benzimidazole and its therapeutic uses were disclosed in European Patent No. 5129.
  • Omeprazole is a well-known gastric acid secretion inhibitor, and is useful as an anti ulcer agent.
  • Omeprazole has a stereogenic center at sulfur and therefore exist as two optical isomers such as R-omeprazole and S-omeprazole (esomeprazole).
  • PCT publication no. WO 97/02261 disclosed a process for the optical purification of certain enantiomerically enriched benzimidazole derivatives by using a crystallization method.
  • U.S. Patent No. 7,176,319 B2 disclosed a resolution of racemic sulfoxide compounds using chiral camphoursulfonyl chloride.
  • U.S. Patent No. 5,948,789 and U.S. Patent No. 7,365,206 B2 disclosed stereoselective oxidation methods for the preparation of chiral substituted 2-(2- pyridinylmethylsulfinyl)-lH-benzimidazoles.
  • omeprazole can be separated or resolved into enantiomers by using BINOL reagent has described in co-pending application no. PCT/IN2009/000634.
  • composition of the enantiomers of omeprazole in the resolution process can be controlled by using variable quantities of BINOL.
  • an object of the present invention is to provide a process for controlling the content of single enantiomer of omeprazole with respect to other enantiomers.
  • room temperature refers to temperature at about 25 to 35°C.
  • a process for controlling the content of single enantiomer of omeprazole with respect to other enantiomers which comprises:
  • BINOL is used in the quantity of 1.0 to 1.2 moles per mole of omeprazole to obtain the product having esomeprazole to R- omeprazole ratio of 99.2:0.8 to 99.9:0.1.
  • BINOL is used in the quantity of 1.3 to 1.5 moles per mole of omeprazole to obtain the product having esomeprazole to R- omeprazole ratio of 99.8:0.2 to 100:0.
  • the reaction in step (a) may preferably be carried out in a solvent selected from methylene chloride, ethylene chloride, chloroform, toluene, xylene, benzene, styrene, cyclohexane, hexane, n-heptane or mixture thereof. More preferably the solvents are methylene chloride and toluene.
  • diastereomers formed in step (a) are then separated. It is well known that diastereomers differ in their properties such as solubility and they can be separated based on the differences in their properties.
  • the separation of the diastereomers can be performed by using the methods known to the person skilled in the art. These methods include chromatographic techniques and fractional crystallization, preferable method being fractional crystallization.
  • Crystallization of preferentially one diastereomer from the solution of diastereomers can be performed by conventional methods such as cooling, partial removal of solvents, seeding or a combination thereof. Fractional crystallization may also occur from the solution under condition of diasteromeric formation. Isolation can be repeated until the desired chiral purity is obtained. But, usually one or two isolations may be sufficient. The separated solid may be collected by the method known such as centrifugation or filtration.
  • the separated diastereomers is converted into enantiomer of omeprazole in step
  • the cyclic amine used in the process may be five or six member cyclic amine salts. More preferably the five and six member cyclic amine salts is selected from piperidine, pyrrolidine and piperazine, and still more preferably the six member cyclic amine salt is piperidine.
  • the solvent used in the process may be selected from water, methylene chloride, ethylene chloride, chloroform, toluene, xylene, benzene, styrene, cyclohexane, hexane, n-heptane, methanol, ethanol, isopropyl alcohol, n-butanol, acetone, methyl ethyl ketone, methyl isobutyl ketone and diethyl ketone. More preferably the solvents are water, toluene, methylene chloride, acetone and methanol.
  • Vanadyl acetylacetonate (4.8 gm) was added to water (210 ml) and then cooled to 0 to 10°C. To the reaction mixture was added hydrogen peroxide (50 %, 120 ml) at 0 to 10°C and stirred for 20 minutes. 5-Methyoxy-2-[[(4-methoxy-3,5-dimethylpyridin-2- yl)methyl]thio]-l H-benzimidazole (480 gm) and acetone (1950 ml) were added to the reaction mixture. The reaction mixture was maintained for 3 hours 30 minutes at 10 to 15°C and then added sodium hydroxide (46 %, 16 ml) and water (1600 ml).

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

Abstract

La présente invention concerne un procédé pour contrôler la teneur d'un énantiomère d'oméprazole par rapport à d'autres énantiomères.
PCT/IN2011/000840 2011-02-01 2011-12-07 Procédé pour contrôler la teneur d'un énantiomère d'oméprazole WO2012104863A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN302/CHE/2011 2011-02-01
IN302CH2011 2011-02-01

Publications (2)

Publication Number Publication Date
WO2012104863A2 true WO2012104863A2 (fr) 2012-08-09
WO2012104863A3 WO2012104863A3 (fr) 2012-10-04

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2011/000840 WO2012104863A2 (fr) 2011-02-01 2011-12-07 Procédé pour contrôler la teneur d'un énantiomère d'oméprazole

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WO (1) WO2012104863A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2980086A1 (fr) 2014-07-29 2016-02-03 F.I.S.- Fabbrica Italiana Sintetici S.p.A. Procédé efficace pour la préparation d'ésoméprazole (S)-binol complexe
CN105418588A (zh) * 2016-01-17 2016-03-23 青岛辰达生物科技有限公司 一种制备高纯度埃索美拉唑镁三水合物的方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080319195A1 (en) * 2005-12-22 2008-12-25 Ratiopharm Gmbh Enantioselective Preparation of Benzimidazole Derivatives and Their Salts
US20100160639A1 (en) * 2006-07-05 2010-06-24 Lupin Limited Process for the preparation of optically pure or optically enriched enantiomers of sulphoxide compounds
WO2010118575A1 (fr) * 2009-04-16 2010-10-21 Chengdu Organic Chemicals Co., Ltd, Chinese Academy Of Science Résolution d'énantiomères racémiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080319195A1 (en) * 2005-12-22 2008-12-25 Ratiopharm Gmbh Enantioselective Preparation of Benzimidazole Derivatives and Their Salts
US20100160639A1 (en) * 2006-07-05 2010-06-24 Lupin Limited Process for the preparation of optically pure or optically enriched enantiomers of sulphoxide compounds
WO2010118575A1 (fr) * 2009-04-16 2010-10-21 Chengdu Organic Chemicals Co., Ltd, Chinese Academy Of Science Résolution d'énantiomères racémiques

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2980086A1 (fr) 2014-07-29 2016-02-03 F.I.S.- Fabbrica Italiana Sintetici S.p.A. Procédé efficace pour la préparation d'ésoméprazole (S)-binol complexe
US9428486B1 (en) 2014-07-29 2016-08-30 F.I.S.—Fabbrica Italiana Sintetici S.p.A. Efficient process for the preparation of Esomeprazole (S)-Binol complex
CN105418588A (zh) * 2016-01-17 2016-03-23 青岛辰达生物科技有限公司 一种制备高纯度埃索美拉唑镁三水合物的方法

Also Published As

Publication number Publication date
WO2012104863A3 (fr) 2012-10-04

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