WO1999047514A1 - Procede chimique d'obtention de derives de sulphinyle par oxydation des coderives correspondants avec des perborates - Google Patents

Procede chimique d'obtention de derives de sulphinyle par oxydation des coderives correspondants avec des perborates Download PDF

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Publication number
WO1999047514A1
WO1999047514A1 PCT/EP1999/001574 EP9901574W WO9947514A1 WO 1999047514 A1 WO1999047514 A1 WO 1999047514A1 EP 9901574 W EP9901574 W EP 9901574W WO 9947514 A1 WO9947514 A1 WO 9947514A1
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WIPO (PCT)
Prior art keywords
process according
compound
formula
range
och
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Application number
PCT/EP1999/001574
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English (en)
Inventor
James Patrick Brennan
Andrew Timothy Turner
Original Assignee
Knoll Aktiengesellschaft
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 Knoll Aktiengesellschaft filed Critical Knoll Aktiengesellschaft
Priority to CA002323422A priority Critical patent/CA2323422A1/fr
Priority to BR9908835-5A priority patent/BR9908835A/pt
Priority to JP2000536710A priority patent/JP2002506862A/ja
Priority to EP99915569A priority patent/EP1071678A1/fr
Priority to SK1345-2000A priority patent/SK13452000A3/sk
Priority to HU0101230A priority patent/HUP0101230A3/hu
Priority to KR1020007010261A priority patent/KR20010041948A/ko
Priority to IL13800199A priority patent/IL138001A0/xx
Priority to AU34106/99A priority patent/AU3410699A/en
Publication of WO1999047514A1 publication Critical patent/WO1999047514A1/fr
Priority to NO20004580A priority patent/NO20004580D0/no

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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
    • 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 describes an improved process for the preparation of substituted 2-(2-pyridylmethyl)sulphinyl-1H-benzimidazoles particularly omeprazole, lansoprazole and pantoprazole by oxidising the corresponding substituted 2-(2- pyridylmethylthio)-1H-benzimidazole.
  • the present invention provides a process for the preparation of a compound of formula I
  • the perborate salt is a metallic perborate salt or an ammonium perborate salt.
  • the perborate salt may be anhydrous or hydrated.
  • the perborate salt is potassium or sodium perborate. More preferably the perborate salt is sodium perborate. Most preferably the perborate salt is sodium perborate monohydrate or sodium perborate tetrahydrate.
  • the amount of perborate salt employed in the process is in the range of 0.8 to 3 moles per mole of the compound of formula II employed in the process.
  • the amount of perborate employed is in the range 0.95-2.0 moles per mole of the compound of formula II employed in the process. More preferably the amount of perborate employed is in the range 1.0-1.9 moles per mole of the compound of formula II employed in the process for example 1.1-1.5 moles per mole of the compound of formula II. Most preferably the amount of perborate employed is in the range 1.4-1.8 moles per mole of the compound of formula II employed in the process.
  • liquid diluent The purpose of the liquid diluent is to allow contact between the compound of formula II and the perborate salt at the required temperature. Any liquid diluent, which is inert to the reactants, in which this purpose is achieved may be used.
  • the liquid diluent is selected from water, a C 1 . alcohol, toluene, tetrahydrofuran, acetone, a C 2 - 6 diol, a C 3 - 6 triol, ethyl acetate or mixtures thereof. More preferably the liquid diluent is a water/alcohol mixture, for example a water/methanol or a water/ethanol mixture. Most preferably the diluent is a water/methanol mixture optionally containing toluene.
  • the process is carried out at a pH in the range of 8.5 to 12. More preferably 10 to 12. Most preferably the process is carried out at a pH in the range of 10 to 11.
  • the pH of the process is controlled by the addition of a base for example an alkali metal hydroxide an alkali metal carbonate, an alkali metal bicarbonate or an amine e.g. ammonia or an organic amine or mixtures thereof.
  • a base for example an alkali metal hydroxide an alkali metal carbonate, an alkali metal bicarbonate or an amine e.g. ammonia or an organic amine or mixtures thereof.
  • the base is sodium hydroxide.
  • the process is carried out at a temperature in the range of 0 to 150°C and more preferably in the range of 15 to 115°C.
  • the process 4 is carried out at a temperature in the range of 40 to 55°C, particularly at a temperature in the range of 45 to 50°C.
  • the process of the present invention has several advantages over previously described oxidation processes.
  • the reagents employed are cheap, non-hazardous and environmentally friendly, for example sodium perborate is used in domestic washing powder, in mouth washes and in cleaning fluids for contact lenses.
  • Sodium perborate has exceptional storage stability and is not shock sensitive.
  • the process gives good yields reproducibly and provides a product of high purity which is chemically more stable than the products of other oxidation processes especially those carried out in acidic conditions.
  • environmentally friendly liquid diluents may be used.
  • the process of the present invention has two further advantages over the prior art processes. Firstly, this process step may be combined with the previous process step and thus avoid isolation of the compound of formula II. This leads to cost reduction in the process through improved processing times. Secondly, in comparative experiments sodium perborate appears to give fewer impurities arising from over-oxidation, for example formation of a sulphone, or an ⁇ /-oxide, or a sulphone ⁇ /-oxide, than previously known oxidants, for example 3-chloroperoxy- benzoic acid.
  • the desired product can be isolated from the reaction mixture and purified by conventional means e.g. extraction and recrystallisation or filtration followed optionally by recrystallisation.
  • a compound of formula lla is reacted with sodium perborate in a mixture of water and methanol at a pH in the range of 8.5 to 10 at a temperature in the range of 15 -115°C to give a compound of formula la (omeprazole).
  • the compound of formula II is prepared by reacting a compound of formula III
  • the purpose of the second liquid diluent is to allow contact between the compound of formula III and the compound of formula IV at the required temperature.
  • Any liquid diluent, which is inert to the reactants, in which this purpose is achieved may be used.
  • the reaction of III and IV is carried out at a temperature in the range of 10-100°C, preferably at a temperature in the range of 20-80°C and more preferably at a temperature in the range of 40-60°C.
  • the second liquid diluent is selected from water, a M alcohol, toluene, tetrahydrofuran, acetone, a C 2 - 6 diol, a C 3 . 6 triol, ethyl acetate or mixtures thereof. More preferably the second liquid diluent is a water/alcohol mixture, for example a water/methanol or a water/ethanol mixture. Most preferably the diluent is a water/methanol mixture optionally containing toluene. Especially preferably the second liquid diluent is the same as the first liquid diluent. This avoids further processing for example diluent exchange. 6
  • the compound of formula III is present as the free thiol, initially, and the process is carried out in the presence of a base.
  • a base is an alkali metal hydroxide for example sodium hydroxide or potassium hydroxide. More preferably the base is sodium hydroxide.
  • the compound of formula IV is present as a salt and sufficient base is used in the process to neutralise the salt of the compound of formula IV and to form a salt of the compound of formula III.
  • the salt of the compound of formula IV is the hydrochloride salt, the hydrobromide salt, the acetate salt, the nitrate salt or a salt of sulphuric acid or the salt of a phosphoric acid.
  • the salt is the hydrochloride salt.
  • the amount of base employed is in the range of 2.0 to 5.0 moles per mole of the compound of formula III. More preferably the amount of base employed is in the range of 3 to 4 moles per mole of the compound of formula III.
  • a purification solvent is added at the end of the oxidation reaction.
  • the purification solvent has been found to remove certain impurities from the crude reaction product by dissolving these impurities so that on filtration the product obtained requires fewer recrystallisations than would otherwise be necessary. This provides time and energy and therefore cost savings in the process.
  • the purification solvent also aids the filtration process by changing the physical nature of the product so that it can be more readily filtered.
  • the purification solvent is immiscible with the liquid diluent.
  • Preferred purification solvents are hydrocarbons, including aliphatic and aromatic hydrocarbons, and ethers, particularly di(C 1 . 6 alkyl) ethers in which the alkyl groups are the same or different, and esters, for example ethyl acetate and mixtures thereof. More preferably the purification solvent is tert-butyl methyl ether, diisopropyl ether, hexane , heptane or toluene and mixtures thereof. Most preferably the purification solvent is tetf-butyl methyl ether, diisopropyl ether or hexane and mixtures thereof. Especially preferably the purification solvent is tetf-butyl methyl ether or diisopropyl ether. 7
  • the invention is illustrated by the following Examples which are given by way of example only.
  • the final product of each of these Examples was characterised by one or more of the following procedures: high performance liquid chromatography; elemental analysis, nuclear magnetic resonance spectroscopy, infrared spectroscopy and high resolution mass spectroscopy.
  • the compounds of formula II, III and IV used in the Examples were either commercially available or were prepared by the methods given in EP5129, EP174.726 or EP166,287 which are incorporated herein by reference.
  • a solution of sodium hydroxide pellets (0.32 g), sodium perborate tetrahydrate (1.43 g) and water (35 ml) was prepared by stirring and heating the mixed components until a solution was obtained, and was then added dropwise with stirring over 2.5 hours to a solution of 5-methoxy-2- ⁇ [(4-methoxy-3,5-dimethyl- pyridin-2-yl)methyl]thio ⁇ -1H-benzimidazole (2.0 g) in methanol (20 ml) and toluene (2 ml) which was boiling under reflux. The methanol was removed under reduced pressure and the residue was cooled to 50°C and then added to saturated sodium bicarbonate solution (20 ml).
  • a solution was prepared by dissolving sodium hydroxide pellets (17.7 g) and sodium perborate tetrahydrate (68.3 g) in water (1085 ml) with stirring and heating and this solution was then added dropwise to a solution of 5-methoxy-2- ⁇ [(4- methoxy-3,5-dimethyl-pyridin-2-yl)methyl]thio ⁇ -1H-benzimidazole (83.4 g) in methanol (834 ml) whilst the mixture was boiled under reflux. The methanol was removed under reduced pressure and the residue was cooled to 50°C and then added to saturated sodium bicarbonate solution (830 ml). The mixture was cooled to 30°C and extracted with dichloromethane (2 x 400 ml).
  • a solution of sodium hydroxide (1.0 g) and sodium perborate tetrahydrate (3.8 g) in water (65.0 ml) was prepared by heating and stirring. This solution was then added dropwise to a solution of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)pyrid-2- ylmethylthio]-1H-benzimidazole (5.0 g) in methanol (50.0 ml) which was being boiled over 2 hours at reflux with stirring. The mixture was stirred and boiled for a further 15 minutes, then the methanol and water were removed under reduced pressure to give a residue which was cooled to 50°C and added to saturated sodium bicarbonate solution (50.0 ml).
  • the mixture was stirred at 45-50°C for 20 hours. Further sodium perborate tetrahydrate (0.35 g) was added and the mixture was stirred at 45-50°C for a further 3 hours. A final batch of sodium perborate tetrahydrate (0.35 g) was added and the mixture stirred for a further 2 hours at 45-50°C. The mixture was cooled to 35°C and sodium hydrogen carbonate (4.9 g) was added followed by water (16.7 ml) and diisopropyl ether (16.2 ml). The mixture was stirred rapidly at 20-25°C for 1.5 hours.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un procédé pour la préparation d'un composé de formule (I), dans laquelle R1, R2, R3 et R4 représentent a) (R1=CH3; R2=OCH3; R3=CH3; R4=OCH3) ou b) (R1=CH3; R2=OCH2CF3; R3=H; R4=H) ou c) (R1=OCH3; R2=OCH3; R3=H; R4=OCHF2) respectivement et les sels pharmaceutiquement acceptables associés. Ce procédé consiste à faire réagir un composé de formule (II), dans laquelle R1, R2, R3 et R4 représentent a) (R1=CH3; R2=OCH3; R3=CH3; R4=OCH3) ou b) (R1=CH3; R2=OCH2CF3; R3=H; R4=H) ou c) (R1=OCH3; R2=OCH3; R3=H; R4=OCHF2) respectivement avec un sel de perborate dans un diluant liquide à un pH allant de 7,5 à 14 à une température comprise entre 0 °C et le point d'ébullition du diluant liquide utilisé.
PCT/EP1999/001574 1998-03-17 1999-03-11 Procede chimique d'obtention de derives de sulphinyle par oxydation des coderives correspondants avec des perborates WO1999047514A1 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
CA002323422A CA2323422A1 (fr) 1998-03-17 1999-03-11 Procede chimique d'obtention de derives de sulphinyle par oxydation des coderives correspondants avec des perborates
BR9908835-5A BR9908835A (pt) 1998-03-17 1999-03-11 Processo para a preparação de um composto
JP2000536710A JP2002506862A (ja) 1998-03-17 1999-03-11 スルフィニル誘導体を過ホウ酸塩での相応するチオ誘導体の酸化により製造する化学的方法
EP99915569A EP1071678A1 (fr) 1998-03-17 1999-03-11 Procede chimique d'obtention de derives de sulphinyle par oxydation des coderives correspondants avec des perborates
SK1345-2000A SK13452000A3 (sk) 1998-03-17 1999-03-11 Chemický spôsob prípravy sulfinyl-derivátov oxidáciou zodpovedajúcich tio-derivátov s peroxoboritanmi
HU0101230A HUP0101230A3 (en) 1998-03-17 1999-03-11 Chemical process for the production of sulphinyl derivatives by oxidation of the corresponding co-derivatives with perborates
KR1020007010261A KR20010041948A (ko) 1998-03-17 1999-03-11 공유도체를 퍼보레이트로 산화시켜 술피닐 유도체를화학적으로 제조하는 방법
IL13800199A IL138001A0 (en) 1998-03-17 1999-03-11 Chemical process for the production of sulphinyl derivatives by oxidation of the corresponding co-derivatives with perborates
AU34106/99A AU3410699A (en) 1998-03-17 1999-03-11 Chemical process for the production of sulphinyl derivatives by oxidation of the corresponding co-derivatives with perborates
NO20004580A NO20004580D0 (no) 1998-03-17 2000-09-14 Kjemisk fremgangsmÕte for fremstilling av sulfinylderivater ved oksydasjon av de tilsvarende CO-derivater med perborater

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9805558.5 1998-03-17
GBGB9805558.5A GB9805558D0 (en) 1998-03-17 1998-03-17 Chemical process`

Publications (1)

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WO1999047514A1 true WO1999047514A1 (fr) 1999-09-23

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Country Link
EP (1) EP1071678A1 (fr)
JP (1) JP2002506862A (fr)
KR (1) KR20010041948A (fr)
CN (1) CN1293670A (fr)
AU (1) AU3410699A (fr)
BR (1) BR9908835A (fr)
CA (1) CA2323422A1 (fr)
GB (1) GB9805558D0 (fr)
HU (1) HUP0101230A3 (fr)
IL (1) IL138001A0 (fr)
NO (1) NO20004580D0 (fr)
SK (1) SK13452000A3 (fr)
TR (1) TR200002670T2 (fr)
TW (1) TW473476B (fr)
WO (1) WO1999047514A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002062786A1 (fr) * 2001-02-02 2002-08-15 Teva Pharmaceutical Industries Ltd. Procedes de production de 2-(2-pyridylmethyl) sulfinyl-1h-benzimidazoles substitues
JP2003512458A (ja) * 1999-10-28 2003-04-02 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 潰瘍治療薬の製造方法
WO2004052881A3 (fr) * 2002-12-06 2004-11-04 Altana Pharma Ag Procede de preparation de (s)-pantoprazole
US6909004B2 (en) 2002-08-21 2005-06-21 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
WO2004111029A3 (fr) * 2003-06-10 2005-11-17 Teva Pharma Procede de preparation de benzimidazoles 2-[(pyridinyl)methyl]sulfinyle substitues et nouveau derives chlorures de pantoprazole
US7507829B2 (en) 2002-12-19 2009-03-24 Teva Pharmaceuticals Industries, Ltd Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates
US7678816B2 (en) 2003-02-05 2010-03-16 Teva Pharmaceutical Industries Ltd. Method of stabilizing lansoprazole
US7683080B2 (en) 2002-11-18 2010-03-23 Teva Pharmaceutical Industries Ltd. Stable iansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol
US7915422B2 (en) 2004-10-11 2011-03-29 Ranbaxy Laboratories Limited Processes for the preparation of substituted sulfoxides

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100547824B1 (ko) 2001-12-29 2006-02-01 삼성전자주식회사 블루투스를 구비하는 이동통신 단말기에서 긴급구조요청방법
CN102603621B (zh) * 2012-02-07 2013-09-04 成都苑东药业有限公司 一种新型手性亚砜化合物和以该化合物制备埃索美拉唑钠的方法
CN107365300B (zh) * 2017-07-26 2019-08-02 桂林华信制药有限公司 一种有效去除兰索拉唑粗品中杂质的方法

Citations (6)

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Publication number Priority date Publication date Assignee Title
DE2548340A1 (de) * 1974-05-16 1977-05-05 Haessle Ab Benzimidazole, verfahren zu deren herstellung und sie enthaltende mittel
EP0197013A1 (fr) * 1985-03-01 1986-10-08 Aktiebolaget Hässle Benzimidazoles substitués pour la fabrication d'un médicament pour le traitement de maladies intestinales inflammatoires
JPH0352887A (ja) * 1989-07-20 1991-03-07 Yoshitomi Pharmaceut Ind Ltd ピリジン化合物
WO1991019712A1 (fr) * 1990-06-20 1991-12-26 Aktiebolaget Astra Derives de dialcoxy-pyridinyle-benzimidazole, procede de preparation et utilisation pharmaceutique de ces derives
EP0484265A1 (fr) * 1990-10-31 1992-05-06 Centro Genesis Para La Investigacion, S.L. Procédé de préparation d'oméprazol
WO1999002521A1 (fr) * 1997-07-11 1999-01-21 Eisai Co., Ltd. Procedes d'elaboration de derives pyridiniques

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2548340A1 (de) * 1974-05-16 1977-05-05 Haessle Ab Benzimidazole, verfahren zu deren herstellung und sie enthaltende mittel
EP0197013A1 (fr) * 1985-03-01 1986-10-08 Aktiebolaget Hässle Benzimidazoles substitués pour la fabrication d'un médicament pour le traitement de maladies intestinales inflammatoires
JPH0352887A (ja) * 1989-07-20 1991-03-07 Yoshitomi Pharmaceut Ind Ltd ピリジン化合物
WO1991019712A1 (fr) * 1990-06-20 1991-12-26 Aktiebolaget Astra Derives de dialcoxy-pyridinyle-benzimidazole, procede de preparation et utilisation pharmaceutique de ces derives
EP0484265A1 (fr) * 1990-10-31 1992-05-06 Centro Genesis Para La Investigacion, S.L. Procédé de préparation d'oméprazol
WO1999002521A1 (fr) * 1997-07-11 1999-01-21 Eisai Co., Ltd. Procedes d'elaboration de derives pyridiniques

Non-Patent Citations (3)

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Title
FIESER,M.: "SODIUM PERBORAtE", REAGENTS FOR ORGANIC SYNTHESIS, vol. 12, 1986, NEW YORK, pages 452, XP002109649 *
PAQUETTE,L.A.: "SODIUM PERBORATE", ENCYCLOPEDIA OF REAGENTS FOR ORGANIC SYNTHESIS, vol. 7, 1995, CHICHESTER, pages 4611 - 4613, XP002109650 *
PATENT ABSTRACTS OF JAPAN vol. 015, no. 197 (C - 0833) 21 May 1991 (1991-05-21) *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003512458A (ja) * 1999-10-28 2003-04-02 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 潰瘍治療薬の製造方法
US7129358B2 (en) * 2001-02-02 2006-10-31 Teva Pharmaceutical Industries Ltd. Processes for the production of substituted 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles
WO2002062786A1 (fr) * 2001-02-02 2002-08-15 Teva Pharmaceutical Industries Ltd. Procedes de production de 2-(2-pyridylmethyl) sulfinyl-1h-benzimidazoles substitues
CN100347167C (zh) * 2001-02-02 2007-11-07 特瓦制药工业有限公司 取代的2－(2－吡啶基甲基)亚磺酰基－1h－苯并咪唑化合物的生产方法
US7060837B2 (en) 2002-08-21 2006-06-13 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US7022859B2 (en) 2002-08-21 2006-04-04 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US6909004B2 (en) 2002-08-21 2005-06-21 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US7622588B2 (en) 2002-08-21 2009-11-24 Teva Pharmaceutical Industries Ltd. Method for the purification of lansoprazole
US7683080B2 (en) 2002-11-18 2010-03-23 Teva Pharmaceutical Industries Ltd. Stable iansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol
US7301030B2 (en) 2002-12-06 2007-11-27 Nycomed Gmbh Process for preparing (S)-pantoprazole
WO2004052881A3 (fr) * 2002-12-06 2004-11-04 Altana Pharma Ag Procede de preparation de (s)-pantoprazole
US7915423B2 (en) 2002-12-19 2011-03-29 Teva Pharmaceutical Industries, Ltd. Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates
US7507829B2 (en) 2002-12-19 2009-03-24 Teva Pharmaceuticals Industries, Ltd Solid states of pantoprazole sodium, processes for preparing them and processes for preparing known pantoprazole sodium hydrates
US7678816B2 (en) 2003-02-05 2010-03-16 Teva Pharmaceutical Industries Ltd. Method of stabilizing lansoprazole
US7683177B2 (en) 2003-06-10 2010-03-23 Teva Pharmaceutical Industries Ltd Process for preparing 2-[(pyridinyl)methyl]sulfinyl-substituted benzimidazoles and novel chlorinated derivatives of pantoprazole
WO2004111029A3 (fr) * 2003-06-10 2005-11-17 Teva Pharma Procede de preparation de benzimidazoles 2-[(pyridinyl)methyl]sulfinyle substitues et nouveau derives chlorures de pantoprazole
US7915422B2 (en) 2004-10-11 2011-03-29 Ranbaxy Laboratories Limited Processes for the preparation of substituted sulfoxides

Also Published As

Publication number Publication date
EP1071678A1 (fr) 2001-01-31
AU3410699A (en) 1999-10-11
CN1293670A (zh) 2001-05-02
NO20004580L (no) 2000-09-14
HUP0101230A2 (hu) 2001-10-28
HUP0101230A3 (en) 2002-10-28
SK13452000A3 (sk) 2001-04-09
TR200002670T2 (tr) 2000-11-21
BR9908835A (pt) 2000-11-21
IL138001A0 (en) 2001-10-31
NO20004580D0 (no) 2000-09-14
TW473476B (en) 2002-01-21
CA2323422A1 (fr) 1999-09-23
KR20010041948A (ko) 2001-05-25
JP2002506862A (ja) 2002-03-05
GB9805558D0 (en) 1998-05-13

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