WO2009066309A2 - Procédé de préparation d'oméprazole - Google Patents

Procédé de préparation d'oméprazole Download PDF

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Publication number
WO2009066309A2
WO2009066309A2 PCT/IN2008/000445 IN2008000445W WO2009066309A2 WO 2009066309 A2 WO2009066309 A2 WO 2009066309A2 IN 2008000445 W IN2008000445 W IN 2008000445W WO 2009066309 A2 WO2009066309 A2 WO 2009066309A2
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formula
omeprazole
methoxy
process according
methyl
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PCT/IN2008/000445
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English (en)
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WO2009066309A3 (fr
WO2009066309A9 (fr
Inventor
Dhimant Jasubhai Patel
Mahesh Shankarbhai Patel
Shriprakash Dhar Dwivedi
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Cadila Healthcare Limited
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Publication of WO2009066309A2 publication Critical patent/WO2009066309A2/fr
Publication of WO2009066309A3 publication Critical patent/WO2009066309A3/fr
Publication of WO2009066309A9 publication Critical patent/WO2009066309A9/fr

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • the present invention relates to a process for preparing 2- [(pyridinyl)methyl]sulfinyl-substituted benzimidazoles of Formula (I) or a pharmaceutically acceptable salt, hydrate, or solvate thereof. More particularly, the present invention relates to the process for oxidation of 2-[(pyridinyl)methyl]thio- substituted benzimidazoles of Formula (II).
  • Rabeprazole is another compound of the same class and chemically known by
  • Pantoprazole is chemically represented (5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2- pyridinyl)methyl] sulfinyl]-lH-benzimidazole. Pantoprazole useful for short-term treatment of erosive esophagitis associated with gastroesophageal reflux disease (GERD), maintenance of healing of erosive esophagitis and pathological hypersecretory conditions incl ⁇ ding Zollinger-Ellison syndrome.
  • GFD gastroesophageal reflux disease
  • Lansoprazole another compound represented by 2-[[[3-methyl-4(2,2,2,- triflouroethoxy)-2-pyridiyl]methyl]sulfinyl]-lH-benzimidazole and reported in U.S Patent No. 4628098. It is marketed under the brand name Prevacid® for short-term treatment of duodenal ulcer, H. Pylori eradication to prevent recurrence of duodenal ulcer and maintenance of healed duodenal ulcers.
  • thioether is oxidized by using 0.96 equivalent (on a purity basis) of m-chloroperbenzoic acid, to produce sulfoxide at a yield of 80%, which is not an industrially satisfactory yield.
  • the reaction does not ceased at the stage of sulfoxide production but further proceeds to a side reaction where a part of the produced sulfoxide is furthermore oxidized to sulfone as shown below.
  • US 6313303 Bl discloses the process for preparing Rabeprazole, Lansoprazole and other related compounds by oxidation thioether precursor compound with N- halosuccinamide, l,3-dihalo-5,5-dimethylhydantoin or dichloroisocyanurate in the presence of a base.
  • EP 0484265 Al discloses the process for the preparation of omeprazole (see example 32 and 33) by oxidation of 2-(((3,5-dimethyl-4-methoxy-2- pyridinyl)methyl)sulfinyl)-5-methoxy-lH-benzimidazole in suitable organic solvent with 50% H 2 O 2 in presence of catalyst like (P(W 3 O 10 ) 4 .X.H 2 O; ammonium Molybdate, having the formula (NH 4 ) 2 MoO 4 ; sodium tungstate, having the formula Na 2 WO 4 ; phosphomolybdic acid, having the formula H 3 (P(Mo 3 O 1O ) 4 -XH 2 O; and silicotungstic acid, having the formula H 4 (Si(W 3 O 1O ) 4 -XH 2 O at lower temperatures.
  • catalyst like P(W 3 O 10 ) 4 .X.H 2 O
  • ammonium Molybdate having the formula (NH 4 ) 2 Mo
  • U.S. Patent No. 6,147,103 and U.S. Patent No. 6,166,213 claims 5-methoxy-2- [[4-methoxy-3 ,5 -dimethyl-2-pyridinyl)methyl] sulfinyl] - 1 H-benzimidazole (omeprazole) containing less than three parts per million (p.p.m) of residual aromatic hydrocarbon solvent and less than 20 p.p.m of residual methanol relative to omperazole.
  • omeprazole is very essential and hence, the process of the present invention provides omeprazole with all the known and unknown individual impurities well within the phamacopial limits.
  • U.S. Patent No. 6,150,380 discloses two polymorphic forms of Omeprazole. Form A and Form B. Form A and Form B are characterized by XRD, Raman Spectra, single crystal, IR etc. analytical evidences. According, to the disclosure in US '380, the single crystal data and the molecular structure prepared according to EP 5129 and as disclosed in Acta Cryst. (1989), C45, 1921-1923 by Ohishi et al. is omeprazole Form-B.
  • Eur. Patent No. 1,390,360 claims yet another crystalline Form of omeprazole i.e. omeprazole Form C characterized by X-ray powder diffraction pattern exhibiting the d-spacings, single crystal analysis and IR. Also claimed is the process for the preparation of omeprazole Form C by dissolving crude omeprazole in a solvent or a mixture of solvents in which omeprazole is freely soluble, and precipitating Omeprazole Form C with a solvent in which omeprazole is poorly soluble.
  • WO 2007008588 A2 discloses the process for the preparation of omeprazole Form-B free from Form- A after being kept under stability for 3 to 6 months at 2 0 C to 8 0 C at 60% RH.
  • Another object of the present invention to provide a process for preparing 2-(2- pyridylmethyl) sulfinyl-lH-benzimidazoles of formula (I), which is simple, easy to handle and cost effective.
  • R 1 is selected from the group consisting of hydrogen or substituted or unsubstituted Q.Qalkoxy
  • R 2 and R 4 are independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl or C 1 -C 4 alkoxy
  • R 3 is selected from the group consisting of substituted or unsubstituted Q-C 4 alkoxy; which comprises oxidizing thioether compound of formula (II)
  • R 1 represents substituted alkoxy substantially as hereinbefore described
  • suitable substituents is selected from the group consisting of hydrogen or substituted or unsubstituted Ci-C 4 alkoxy, especially methoxy.
  • R 3 represents substituted alkoxy substantially as hereinbefore described
  • suitable substituents one or more alkoxy substituents, such as C 1 -C 3 alkoxy, especially methoxy.
  • R 1 is selected from hydrogen atom, methoxy group or difluoromethoxy group; represents methyl group or methoxy group;
  • R 2 represents methyl group or methoxy group;
  • R 3 represents methoxy group, or 2,2,2- trifluoroethoxy group; and
  • R 4 represents hydrogen atom or methyl group.
  • a preferred compound prepared according to a process of the present invention is lansoprazole, wherein in formula (I) R 4 represents methyl, R 3 represents trifluoroethoxy, R 2 represents hydrogen and R 1 represents hydrogen.
  • a further preferred compound prepared according to a process of the present invention is omeprazole, wherein in formula (I) R 4 represents methyl, R 3 represents methoxy, R2 represents methyl and R 1 represents methoxy.
  • a further preferred compound prepared according to a process of the present invention is pantoprazole, wherein in formula (I) R 4 represents methoxy, R 3 represents methoxy, R 2 represents hydrogen and R 1 represents difluoromethoxy.
  • a further preferred compound prepared according to a process of the present invention is rabeprazole, wherein in formula (I) R 4 represents methyl, R 3 represents - OCH 2 CH 2 CH 2 OMe, R 2 represents hydrogen and R 1 represents hydrogen.
  • the present invention provides an improved process for oxidation of (2-[[[4-(3-methoxy-propoxy)3-methyl-2-pyridinyl]methyl]- thio]-lH- benzimidazole, to the corresponding (2-[[[4-(3-methoxy-propoxy)3-methyl-2- pyridinyl] methyl] -sulfinyl]-lH-benzimidazole or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
  • the present invention provides an improved process for oxidation of (2-[[[3-methyl-4-(2,2,2-trifluoro-ethoxy)-2- pyridinyl]methyl]thio]-lH- benzimidazole to the corresponding (2-[[[3-methyl-4-
  • the present invention provides an improved process for oxidation of ((5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyirdyl)methyl]- thio]-lH-benzimidazole, to the corresponding ((5-methoxy-2-[[(4-methoxy-3,5- dimethyl-2-pyirdyl)methyl]-sulfinyl]-lH-benzimidazole or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
  • the present invention provides an improved process for oxidation of ((5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2- pyridinyl)methyl]thio]-lH-benzimidazole, to the corresponding ((5-(difluoromethoxy)-
  • an improved process for preparing crystalline omeprazole Form-B having purity of atleast 99.70% but not more than 99.90% by HPLC which comprises:
  • oxidizing agent can be selected from m-chlorperbenozic acid, hydrogen peroxide, N-chlorosuccinimide, N- bromosuccinimide, vanadium acetlacetonate and the like.
  • the preferred oxidizing agent is 50% solution of hydrogen peroxide.
  • Suitable catalyst can be selected from (P(W 3 O 1O ) 4 -X-H 2 O; ammonium Molybdate, having the formula (NFLO 2 MoO 4 ; sodium Molybdate, having the formula Na 2 MoO 4 , sodium tungstate, having the formula Na 2 WO 4 ; phosphomolybdic acid, having the formula H 3 (P(Mo 3 O 1O ) 4 -XH 2 O; and silicotungstic acid, having the formula
  • H 4 (Si(W 3 O 10 ) 4 .XH 2 O preferably sodium Molybdate, having the formula Na 2 MoO 4 .
  • hydrogen peroxide in presence of suitable catalyst itself generates the oxidizing agent.
  • the reaction is preferably carried out in absence of base in an organic solvent for the oxidation of thioether linkage in order to obtain highly pure 2-[(pyridinyl)methyl]sulfinyl-benzimidazoles of formula (I).
  • oxidation of thioether compound of formula (II) is carried out in any solvent, which is inactive to compound of formula (II), or Formula (I).
  • oxidation is carried out in alcohol selected from methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, hydrocarbon selected from toluene, xylene, ether selected from diethyl ether, diisopropyl ether, tetrahydrofuran, ester selected from ethyl acetate, methyl acetate, isopropyl acetate, butyl acetate, dimethylformamide, dimethyl sulfoxide or mixture thereof.
  • the organic solvent used can be selected from alcohol like methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, hydrocarbon selected from toluene, xylene, ether selected from diethyl ether, diisopropyl ether, tetrahydrofuran, ester selected from ethyl acetate, methyl acetate, isopropyl acetate, butyl acetate, dimethylformamide, dimethyl sulfoxide or mixture thereof.
  • Suitable catalyst can be selected from (P(W 3 O 1O ) 4 -X-H 2 O; ammonium Molybdate, having the formula (NH 4 ) 2 MoO 4 ; sodium Molybdate, having the formula Na 2 MoO 4 , sodium tungstate, having the formula Na 2 WO 4 ; phosphomolybdic acid, having the formula H 3 (P(MOaO 10 ) 4 .XH 2 O; and silicotungstic acid, having the formula H 4 (Si(W 3 O 10 ) 4 .XH 2 O, preferably sodium Molybdate, having the formula Na 2 MoO 4
  • the substantially pure compound of formula (I) is further isolated by well know techniques used in the art such as filtration, concentration followed by drying.
  • the invention further provides a process for the preparation of omeprazole of Formula (Ha) and its pharmaceutically acceptable salts, solvents, hydrates thereof, which comprises
  • Omeprazole consist higher purity i.e. greater than 99.0% but not more than 99.90%.
  • ((5-methoxy- 2-[[(4-methoxy-3,5-dimethyl-2-pyirdyl)methyl]-thio]-lH-benzimidazole of formula of formula (Ha) was dissolved in the organic solvent preferably ethereal solvent such diethyl etherl, isopropyl ether, tetrahydrofuran, dioxane; alcoholic solvent such as methanol, ethanol, isopropanol, n-propanol to obtain the solution.
  • the organic solvent preferably ethereal solvent such diethyl etherl, isopropyl ether, tetrahydrofuran, dioxane
  • alcoholic solvent such as methanol, ethanol, isopropanol, n-propanol
  • the said solution of compound of formula (Ha) is oxidized with 50% hydrogen peroxide in presence of sodium, molybdate catalyst.
  • the reaction is preferably carried out at temperature of -10 to 50° C. More preferably, the reaction is carried out at about -5° to 10° C.
  • the complete reaction time is about 10 minutes to about 3 hours.
  • Suitable organic solvent can be selected from alcoholic solvent like methanol, ethanol, isopropanol, propanol etc, preferably mixture of isopropanol with water to obtain optimum result in terms of better purity and better yield.
  • the isolated omeprazole crude is treated with base selected from alkali metal or alkaline earth metal hydroxides like sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, lithium hydroxide and the like, alkali metal or alkaline earth metal carbonates or bicarbonates like sodium carbonate, potassium carbonate, calcium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate and the like, preferably sodium hydroxide.
  • base selected from alkali metal or alkaline earth metal hydroxides like sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide, lithium hydroxide and the like, alkali metal or alkaline earth metal carbonates or bicarbonates like sodium carbonate, potassium carbonate, calcium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate and the like, preferably sodium hydroxide.
  • the reaction of crude omeprazole with base can be carried out in suitable organic solvent selected from alcohols like methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol; hydrocarbons like toluene, xylene, ethylbenzene; ethers like diethyl ether, diisopropyl ether, tetrahydrofuran; esters like ethyl acetate ⁇ methyl acetate, isopropyl acetate, butyl acetate; dimethylformamide, dimethyl sulfoxide or mixture thereof with water, preferably methanol or mixture thereof with water.
  • suitable organic solvent selected from alcohols like methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol; hydrocarbons like toluene, xylene, ethylbenzene; ethers like dieth
  • the product, pure omeprazole Form-B is isolated by treating the reaction mixture with weak acid like acetic acid and characterized by known methods like XRD, DSC and IR.
  • the crystalline omeprazole form-B characterized by having atleast one of the following properties:
  • crystalline omeprazole Form-B is characterized by a powder x-ray diffraction (PXRD) having characteristic peaks at about 9.7, 8.0, 7.9, 7.1, 5.9, 5.6, 5.3, 5.1, and 4.5 d- values ⁇ 0.04 (A).
  • PXRD powder x-ray diffraction
  • crystalline omeprazole Form-B is characterized by differential scanning calorimetry analysis having endothermic peak at about 158.3 0 C.
  • a crystalline omeprazole Form-B is also characterized by IR having characteristic peaks at about 545, 821, 1011, 1017, 1202, 1407, 1587, 3006, 3061 ⁇ 5 cm "1 .
  • a crystalline omeprazole form-B prepared by the process of the present invention is having particle size distribution D 10 less than about 10 ⁇ m, D 50 less than about 20 ⁇ m and D 90 less than about 50 ⁇ m.
  • the purity of Omeprazole can be determined by using high-performance liquid chromatography and residual solvent by gas chromatography. It can be performed by using the known methods as disclosed in U.S. Patents No. 6,191,148, 6,166,213 and 6, 147, 103 are incorporated herein as reference.
  • HPLC purity of omeprazole form-B obtained in the following examples were determined by following HPLC (high performance liquid chromatography) conditions listed below:
  • FIG. I X-ray diffraction pattern of omeprazole Form-B as obtained in example 3.
  • FIG. II Differential Scanning Calorimetry analysis of omeprazole Form-B as obtained in example 3.
  • FIG. Ill Infrared spectra analysis of omeprazole Form-B as obtained in example 3.
  • the reaction mixture was maintained for 5-6 hours at 5 0 C to 1O 0 C. 8.9 gm of sodium thiosulphate in 40 mL of water was added within 30 mins. The pH was adjusted by 10% NaOH solution. The product was filtered, washed with chilled mixture of methanol and water and dried at 5O 0 C to 55 0 C to obtain 78 gm of crude omeprazole.
  • Example-2 Preparation of 5-methoxy-2-[[4-methoxy-3,5-dimethyl-2- py ridiny l)methy 1] sulfiny 1] - IH-
  • the reaction mixture was maintained for 5-6 hours at 5 0 C to 1O 0 C. 8.9 gm of sodium thiosulphate in 40 mL of water was added within 30 mins. The product was filtered, washed with chilled mixture of ethanol and water and dried at 5O 0 C to 55 0 C to obtain 79 gm of crude omeprazole.
  • Example-3 Purification of 5-methoxy-2-[[4-methoxy-3,5-dimethyl-2- pyridinyl)methyl]sulfinyl]-lH-benzimidazole (omeprazole Form-B)
  • Impurity-A 5-methoxy- 1 H-benzimidazole-2-thiol
  • Impurity-B 2-[(R,S)]-[(3,5-dimethylpyridine-2-yl)methyl]sulphinyl]-5-methoxy-lH- benzimidazole
  • Impurity-C 5 -methoxy-2 [ [4-methoxy-3 ,5 -dimethylpyridi ⁇ -2-yl)methyl] sulphanyl] - lH-benzimidazole [Omeprazole Sulfide]
  • Impurity-D 5 -methoxy-2 [ [4-methoxy-3 ,5 -dirnethylpyridin-2-yl)methyl] sulphonyl] - lH-benzimidazole [Omeprazole Sulfone]
  • Impurity-E 4-methoxy-2-[[(R,S)-(5-methoxy-lH-benzimidazole-2-yl)- sulphinyl]methyl)-3 ,5 -dimethylpyridine- 1 -oxide [Omeprazole N-Oxide]
  • the present invention provides an improved process for the preparation of Omeprazole Form-B.
  • the present invention provides an improved process for the preparation of Omeprazole F ⁇ rm-B having purity of atleast 99.75% but not more than 99.90% by area percentage of HPLC.
  • the present invention provides an improved process for the purification of crude omeprazole to obtain polymorphic Form-B.
  • Omeprazole Polymorphic Form-B is substantially free from other crystalline forms of Omeprazole.
  • the present invention provides a simple, cost effective and large scale applicable process for the preparation of Omeprazole Form-B having purity greater than 99.70% but not more than 99.90% by area percentage of HPLC as well as meeting with the Pharmacopial limits of individual impurities.

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Abstract

La présente invention concerne un procédé permettant de préparer des benzimidazoles à substitution 2-[(pyridinyl)méthyl]sulfinyle, représentés par la formule (I) ou un sel, hydrate, ou solvate pharmaceutiquement acceptable de ces composés. Plus particulièrement, la présente invention concerne le procédé d'oxydation de benzimidazoles à substitution 2-[(pyridinyl)méthyl]thio, représentés par la formule (II).
PCT/IN2008/000445 2007-07-12 2008-07-11 Procédé de préparation d'oméprazole WO2009066309A2 (fr)

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IN1335MU2007 2007-07-12

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WO2009066309A9 WO2009066309A9 (fr) 2010-05-14

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112229920A (zh) * 2020-09-17 2021-01-15 海南中玉药业有限公司 一种艾司奥美拉唑钠潜在基因毒性杂质的检测方法
US20230012374A1 (en) * 2019-10-31 2023-01-12 Kumiai Chemical Industry Co., Ltd. Process for producing herbicide and intermediate thereof
CN115785067A (zh) * 2023-01-19 2023-03-14 北京京卫燕康药物研究所有限公司 一种艾司奥美拉唑硫醚的杂质化合物的制备方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0302720A1 (fr) * 1987-08-04 1989-02-08 Takeda Chemical Industries, Ltd. Préparation de composés 2-(2-pyridylméthylsulfinyl)-benzimidazoliques
EP0484265A1 (fr) * 1990-10-31 1992-05-06 Centro Genesis Para La Investigacion, S.L. Procédé de préparation d'oméprazol
ES2036948A1 (es) * 1991-11-21 1993-06-01 Genesis Para La Investigacion Procedimiento de obtencion de compuestos derivados de piridina.
EP1085019A1 (fr) * 1999-09-13 2001-03-21 Cipla Limited Procédé de préparation d'Oméprazole
EP1270555A1 (fr) * 2000-03-13 2003-01-02 Esteve Quimica, S.A. Procede d'oxydation d'un groupe thioether en groupe sulfoxyde
US6956137B1 (en) * 1999-04-13 2005-10-18 Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg Singlet oxygen oxidation of organic substrates
US20060128964A1 (en) * 2004-12-10 2006-06-15 Industrial Technology Research Institute Method for preparing 2- (2-pyridylmethylsulphinyl) benzimidazoles
EP1790647A1 (fr) * 2004-09-13 2007-05-30 Takeda Pharmaceutical Company Limited Procede et appareil destines a produire un compose oxyde
EP2030973A1 (fr) * 2007-08-31 2009-03-04 KRKA, tovarna zdravil, d.d., Novo mesto Procédé pour la préparation de 2-sulfinyl-1H-benzimidazoles

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0302720A1 (fr) * 1987-08-04 1989-02-08 Takeda Chemical Industries, Ltd. Préparation de composés 2-(2-pyridylméthylsulfinyl)-benzimidazoliques
EP0484265A1 (fr) * 1990-10-31 1992-05-06 Centro Genesis Para La Investigacion, S.L. Procédé de préparation d'oméprazol
ES2036948A1 (es) * 1991-11-21 1993-06-01 Genesis Para La Investigacion Procedimiento de obtencion de compuestos derivados de piridina.
US6956137B1 (en) * 1999-04-13 2005-10-18 Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg Singlet oxygen oxidation of organic substrates
EP1085019A1 (fr) * 1999-09-13 2001-03-21 Cipla Limited Procédé de préparation d'Oméprazole
EP1270555A1 (fr) * 2000-03-13 2003-01-02 Esteve Quimica, S.A. Procede d'oxydation d'un groupe thioether en groupe sulfoxyde
EP1790647A1 (fr) * 2004-09-13 2007-05-30 Takeda Pharmaceutical Company Limited Procede et appareil destines a produire un compose oxyde
US20060128964A1 (en) * 2004-12-10 2006-06-15 Industrial Technology Research Institute Method for preparing 2- (2-pyridylmethylsulphinyl) benzimidazoles
EP2030973A1 (fr) * 2007-08-31 2009-03-04 KRKA, tovarna zdravil, d.d., Novo mesto Procédé pour la préparation de 2-sulfinyl-1H-benzimidazoles

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHMURZYNSKI L: "Studies on correlations of acid-base properties of substituted pyridine N-oxides in solutions. Correlations of cationic homoconjugation constants and pK(a) values in non-aqueous media" ANALYTICA CHIMICA ACTA 19961120 NL, vol. 334, no. 1-2, 20 November 1996 (1996-11-20), pages 155-159, XP002536936 ISSN: 0003-2670 *
MADESCLAIRE M: "SYNTHESIS OF SULFOXIDES BY OXIDATION OF THIOETHERS" TETRAHEDRON, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 42, no. 20, 1 January 1986 (1986-01-01), pages 5459-5495, XP001026077 ISSN: 0040-4020 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230012374A1 (en) * 2019-10-31 2023-01-12 Kumiai Chemical Industry Co., Ltd. Process for producing herbicide and intermediate thereof
CN112229920A (zh) * 2020-09-17 2021-01-15 海南中玉药业有限公司 一种艾司奥美拉唑钠潜在基因毒性杂质的检测方法
CN112229920B (zh) * 2020-09-17 2022-10-21 海南中玉药业有限公司 一种艾司奥美拉唑钠潜在基因毒性杂质的检测方法
CN115785067A (zh) * 2023-01-19 2023-03-14 北京京卫燕康药物研究所有限公司 一种艾司奥美拉唑硫醚的杂质化合物的制备方法

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