CN1040536C - 改进的合成奥美普拉唑的方法 - Google Patents

改进的合成奥美普拉唑的方法 Download PDF

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CN1040536C
CN1040536C CN91103923A CN91103923A CN1040536C CN 1040536 C CN1040536 C CN 1040536C CN 91103923 A CN91103923 A CN 91103923A CN 91103923 A CN91103923 A CN 91103923A CN 1040536 C CN1040536 C CN 1040536C
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alkyl formate
aomei
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CN1058211A (zh
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阿尼·E·布兰斯特伦
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AstraZeneca AB
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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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract

在二氯甲烷溶液中和pH基本保持在8.0-8.6左右的条件下，将5-甲氧基-2-[(4-甲氧基-3，5-二甲基-2-吡啶基]-甲硫基]-1H-苯咪唑(化合物Ⅰ)与间氯过苯甲酸反应，用NaOH水溶液提取反应混合物，分离水相和有机相，将甲酸烷基酯加到水相中，生成奥美普拉唑结晶。

Description

改进的合成奥美普拉唑的方法
本发明涉及5-甲氧基-2-[[(4-甲氧基-3，5-二甲基-2-吡啶基)-甲基]亚磺酰-1H-苯并咪唑改进的合成方法，为方便起见，在以下的说明书和权利要求书中将该化合物简称为奥美普拉唑(omeprazole)。
US-A-4255431公开了奥美普拉唑的合成方法，包括将5-甲氧基-2-[(-4甲氧基-3，5-二甲基-2-吡啶基-)-甲硫基]-1H-苯并咪唑在二氯甲烷溶液中与间氯过苯甲酸反应，生成奥美普拉唑和间氯苯甲酸。奥美普拉唑对酸非常敏感，反应混合物必须保存在低温条件下，以防止在反应混合物中过量分解。
该产物通过滤去反应期间生成的间氯苯甲酸后得到，滤液用二氯甲烷稀释，经Na2CO3溶液提取，干燥和蒸发。生成的奥美普拉唑产物由于存在起始原料和副产物而被污染。
本发明的任务在于提供改进奥美普拉唑的合成方法，以摒除以往已知各种方法的种种缺点。
根据本发明的方法，可以完成上述任务。该方法的特征在于在二氯甲烷溶液中和基本保持约8.0-8.6的pH值的条件下，将5-甲氧基-2-[(4-甲氧基-3，5-二甲基-2-吡啶基)-甲硫基]-1H-苯并咪唑(以下用化合物I表示)与间氯过苯甲酸反应，用NaOH水溶液提取反应物，分离水相与有机相，将甲酸烷基酯加到水相中，生成奥美普拉唑结晶。
间氯过苯甲酸的用量为每摩尔化合物I0.7-1.4摩尔当量较为适宜，尤以每摩尔化合物I用0.9-1.2摩尔当量为佳。
按本发明的一个实施例，甲酸烷基酯是甲酸甲酯或甲酸乙酯，以甲酸甲酯为佳。
甲酸烷基酯的用量为每摩尔化合物I1.2-2.0摩尔当量较为适宜，尤以每摩尔化合物I用1.5-1.8摩尔当量为佳。
本发明方法的一个重要特征在于，由于用NaOH水溶液提取，未反应的硫化物并不转化为水相，另一个重要特征在于由于将甲酸甲酯加到水相中，间氯苯甲酸并不结晶，从而省去了已知方法中必须过滤间氯苯甲酸的步骤。
用NaOH的pH静态滴定方法或使用缓冲溶液，使反应混合物的pH值保持在8.0-8.6范围内。较佳的缓冲溶液是碳酸氢钠和碳酸氢钾。
本发明方法的一个重要优点在于反应是在二氯甲烷有机相中进行的，在使用缓冲液的情况下，反应期间形成的间氯苯甲酸进入到含缓冲液的水相中。由此所生成的奥美普拉唑并不与酸接触，并且反应可在0℃以上的温度条件下完成。
按本发明的一个实施例，NaOH水相的pH值保持在大约12以上。
按本发明的另一个实施例，奥美普拉唑的结晶是在pH9以上的条件下完成。
以下的实施例将进一步说明本发明，但不是限制本发明。
实施例
在pH8.6和CH2Cl2溶液中，5-甲氧基-2-[(4-甲氧基-3，5-二甲基-2-吡啶基)-甲硫基]-1H-苯并咪唑(16.2g；0.0492mol)与间氯过苯甲酸(13.6g；0.0537mol)反应，在KHCO3(5.6g；0.056mol)缓冲液存在下保持反应。加料期间，温度保持在0℃左右。
将经过稀释的NaOH加到pH12以上，分离CH2Cl2相。
将甲酸甲酯(4.7g)加到水相中，在pH保持在9以上的条件下，使奥美普拉唑结晶。在0℃以上温度条件下，滤出结晶，并用水和甲醇洗涤。经过洗涤的结晶在真空下干燥。得率：15.6g(92％)。

Claims (8)

1.改进的奥美普拉唑合成方法，其特征在于在：在二氯甲烷溶液中和pH基本保持在8.0-8.6的条件下，将5-甲氧基-2-[(4-甲氧基-3，5-二甲基-2-吡啶基]-甲硫基]-1H-苯并咪唑(化合物I)与间氯过苯甲酸反应；用pH12以上的NaOH水溶液提取反应混合物；分离水相和有机相；和将甲酸烷基酯加到水相中，在pH9以上生成奥美普拉唑结晶。
2.按权利要求1的方法，其特征在于间氯过苯甲酸以每摩尔化合物I0.7-1.4摩尔当量的量加入。
3.按权利要求2的方法，其特征在于间氯过苯甲酸以每摩尔化合物I0.9-1.2摩尔当量的量加入。
4.按权利要求1或2的方法，其特征在于所述甲酸烷基酯是甲酸甲酯。
5.按权利要求1或2的方法，其特征在于使用缓冲溶液使反应混合物的pH值保持在8.0-8.6的范围内。
6.按权利要求5的方法，其特征在于所述缓冲溶液是碳酸氢钠或碳酸氢钾溶液。
7.按权利要求1或2的方法，其特征在于将甲酸烷基酯以每摩尔化合物I1.2-2.0摩尔当量的量加入。
8.按权利要求7的方法，其特征在于将甲酸烷基酯以每摩尔化合物I1.5-1.8摩尔当量的量加入。
CN91103923A 1990-06-07 1991-06-07 改进的合成奥美普拉唑的方法 Expired - Fee Related CN1040536C (zh)

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SE9002043A SE9002043D0 (sv) 1990-06-07 1990-06-07 Improved method for synthesis

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Families Citing this family (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE521100C2 (sv) * 1995-12-15 2003-09-30 Astra Ab Förfarande för framställning av en bensimidazolförening
US5840737A (en) 1996-01-04 1998-11-24 The Curators Of The University Of Missouri Omeprazole solution and method for using same
US6699885B2 (en) 1996-01-04 2004-03-02 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and methods of using same
US6645988B2 (en) * 1996-01-04 2003-11-11 Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
US6489346B1 (en) 1996-01-04 2002-12-03 The Curators Of The University Of Missouri Substituted benzimidazole dosage forms and method of using same
SK283805B6 (sk) 1996-09-09 2004-02-03 Slovakofarma, A. S. Spôsob prípravy omeprazolu
CA2204580A1 (en) * 1997-05-06 1998-11-06 Michel Zoghbi Synthesis of pharmaceutically useful pyridine derivatives
US6437139B1 (en) 1997-05-06 2002-08-20 Pdi-Research Laboratories, Inc. Synthesis of pharmaceutically useful pyridine derivatives
KR100463031B1 (ko) * 1997-05-26 2005-04-06 동아제약주식회사 5-메톡시-2-[3,5-디메틸-4-메톡시피리딜메틸)설피닐]-1h-벤즈이미다졸의신규제조방법
US6096340A (en) * 1997-11-14 2000-08-01 Andrx Pharmaceuticals, Inc. Omeprazole formulation
US6174548B1 (en) 1998-08-28 2001-01-16 Andrx Pharmaceuticals, Inc. Omeprazole formulation
SE9704183D0 (sv) 1997-11-14 1997-11-14 Astra Ab New process
SI20019A (sl) 1998-07-13 2000-02-29 LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. Izboljšan postopek sinteze 5-metoksi -2-/(4-metoksi-3,5-dimetil-2-piridil)metil/ sulfinil-1H-benzimidazola
US6166213A (en) * 1998-08-11 2000-12-26 Merck & Co., Inc. Omeprazole process and compositions thereof
US6191148B1 (en) 1998-08-11 2001-02-20 Merck & Co., Inc. Omerazole process and compositions thereof
US6733778B1 (en) 1999-08-27 2004-05-11 Andrx Pharmaceuticals, Inc. Omeprazole formulation
UA72748C2 (en) * 1998-11-10 2005-04-15 Astrazeneca Ab A novel crystalline form of omeprazole
IL142703A (en) 1998-11-10 2006-04-10 Astrazeneca Ab Crystalline form of omeprazole
US6362202B1 (en) 1999-03-02 2002-03-26 Sepracor Inc. Methods and compositions using (−) norcisapride in combination with proton pump inhibitors or H2 receptor antagonists
US6353005B1 (en) 1999-03-02 2002-03-05 Sepracor, Inc. Method and compositions using (+) norcisapride in combination with proton pump inhibitors or H2 receptor antagonist
US6262085B1 (en) 1999-08-26 2001-07-17 Robert R. Whittle Alkoxy substituted Benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6312712B1 (en) 1999-08-26 2001-11-06 Robert R. Whittle Method of improving bioavailability
US6369087B1 (en) 1999-08-26 2002-04-09 Robert R. Whittle Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same
US6316020B1 (en) 1999-08-26 2001-11-13 Robert R. Whittle Pharmaceutical formulations
US6312723B1 (en) 1999-08-26 2001-11-06 Robert R. Whittle Pharmaceutical unit dosage form
US6262086B1 (en) 1999-08-26 2001-07-17 Robert R. Whittle Pharmaceutical unit dosage form
US6268385B1 (en) 1999-08-26 2001-07-31 Robert R. Whittle Dry blend pharmaceutical formulations
US6780880B1 (en) * 1999-08-26 2004-08-24 Robert R. Whittle FT-Raman spectroscopic measurement
US6326384B1 (en) 1999-08-26 2001-12-04 Robert R. Whittle Dry blend pharmaceutical unit dosage form
DE19951960C2 (de) 1999-10-28 2002-06-27 Gruenenthal Gmbh Verfahren zur Herstellung als Ulkustherapeutika geeigneter Benzimidazol-Derivate
WO2002062786A1 (en) 2001-02-02 2002-08-15 Teva Pharmaceutical Industries Ltd. Processes for the production of substituted 2-(2-pyridylmethyl) sulfinyl-1h-benzimidazoles
KR100783020B1 (ko) * 2001-03-23 2007-12-07 동아제약주식회사 2-메틸클로라이드 피리딘 유도체 및 이를 이용한 벤즈이미다졸 유도체의 제조 방법
IL159854A0 (en) * 2001-07-16 2004-06-20 Janssen Pharmaceutica Nv Improved process for preparing benzimidazole-type compounds
CA2472103A1 (en) * 2002-01-25 2003-08-07 Santarus, Inc. Transmucosal delivery of proton pump inhibitors
SE0203092D0 (en) 2002-10-18 2002-10-18 Astrazeneca Ab Method for the synthesis of a benzimidazole compound
EP1603537A4 (en) * 2003-02-20 2009-11-04 Santarus Inc IMMEDIATE RELEASE OF OMEPRAZOLE ANTACIDAL COMPLEX WITH NEW FORMULATION FOR RAPID AND PROLONGED ELIMINATION OF GASTRIC ACID
JP2006528181A (ja) * 2003-07-18 2006-12-14 サンタラス インコーポレイティッド 酸分泌を阻害するために有用な薬学的製剤ならびにそれらを作製および使用する方法
AU2004257864A1 (en) * 2003-07-18 2005-01-27 Santarus, Inc. Pharmaceutical formulation and method for treating acid-caused gastrointestinal disorders
US8993599B2 (en) * 2003-07-18 2015-03-31 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US20070292498A1 (en) * 2003-11-05 2007-12-20 Warren Hall Combinations of proton pump inhibitors, sleep aids, buffers and pain relievers
US8815916B2 (en) * 2004-05-25 2014-08-26 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
US8906940B2 (en) * 2004-05-25 2014-12-09 Santarus, Inc. Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them
JP5173191B2 (ja) 2004-09-13 2013-03-27 武田薬品工業株式会社 酸化化合物の製造方法及び製造装置
SI1802584T1 (sl) * 2004-10-11 2010-01-29 Ranbaxy Lab Ltd Postopki za pripravo substituiranih sulfoksidov
KR100641534B1 (ko) 2005-07-28 2006-11-01 한미약품 주식회사 에스오메프라졸 및 그의 염의 제조방법
CA2631581C (en) 2005-12-01 2011-05-03 Auspex Pharmaceuticals, Inc. Substituted phenethylamines with serotoninergic and/or norepinephrinergic activity
EP1801110A1 (en) 2005-12-22 2007-06-27 KRKA, tovarna zdravil, d.d., Novo mesto Esomeprazole arginine salt
WO2007129328A2 (en) * 2006-05-09 2007-11-15 Cadila Healthcare Limited Process for preparing 2-[pyridinyl]sulfinyl-substituted benzimidazoles
US20090092658A1 (en) * 2007-10-05 2009-04-09 Santarus, Inc. Novel formulations of proton pump inhibitors and methods of using these formulations
EA200900985A1 (ru) 2007-01-31 2009-12-30 Крка, Товарна Здравил, Д. Д., Ново Место Способ получения оптически чистого омепразола
WO2008140859A1 (en) 2007-03-15 2008-11-20 Auspex Pharmaceuticals, Inc. Deuterated venlafaxines and 0-desmetylvenlafaxines with serotoninergic and / or norepinephrinergic activity
WO2009122435A2 (en) * 2008-03-31 2009-10-08 Council Of Scientific & Industrial Research A simultaneous method for the preparation of a mixture of 3- acetoxy-17-acetamido-16-formyl-androst-5,17-diene and 3- acetoxy-2'-chloro-5-androsteno[17,16-b]pyridine
WO2010134099A1 (en) 2009-05-21 2010-11-25 Cadila Healthcare Limited One pot process for preparing omeprazole and related compounds
CN102786513A (zh) * 2011-05-18 2012-11-21 中国医学科学院药物研究所 奥美拉唑晶e型物质及制备方法与在药品和保健品中应用
CN104203938A (zh) 2012-01-21 2014-12-10 朱比兰特生命科学有限公司 用于制备2-吡啶基甲基亚硫酰基苯并咪唑、它们的类似物和光学活性对映体的方法
TW202126317A (zh) 2019-09-24 2021-07-16 美商普拉塔生技公司 用於治療發炎和免疫疾病之組成物和方法

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN148930B (zh) * 1977-09-19 1981-07-25 Hoffmann La Roche
SE7804231L (sv) * 1978-04-14 1979-10-15 Haessle Ab Magsyrasekretionsmedel
US4307102A (en) * 1981-02-19 1981-12-22 Sterling Drug Inc. Phenanthro[2,3-c]pyrazole
SE8300736D0 (sv) * 1983-02-11 1983-02-11 Haessle Ab Novel pharmacologically active compounds
ZW4585A1 (en) * 1984-04-19 1985-11-20 Hoffmann La Roche Imidazole derivatives
IL76839A (en) * 1984-10-31 1988-08-31 Byk Gulden Lomberg Chem Fab Picoline derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same
SE8500996D0 (sv) * 1985-03-01 1985-03-01 Haessle Ab Method of treatment
SE8600658D0 (sv) * 1986-02-14 1986-02-14 Haessle Ab Novel composition of matter
FI91754C (fi) * 1986-12-02 1994-08-10 Tanabe Seiyaku Co Analogiamenetelmä lääkeaineena käyttökelpoisen imidatsolijohdannaisen valmistamiseksi
DE3722810A1 (de) * 1987-07-10 1989-01-19 Hoechst Ag Substituierte benzimidazole, verfahren zu deren herstellung, diese enthaltende pharmazeutische zubereitungen und deren verwendung
SE9002206D0 (sv) * 1990-06-20 1990-06-20 Haessle Ab New compounds
WO1993006097A1 (en) * 1991-09-20 1993-04-01 Merck & Co., Inc. Novel process for the preparation of anti-ulcer agents

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ATE162790T1 (de) 1998-02-15
EG19392A (en) 1995-06-29
FI925529A0 (fi) 1992-12-04
SA91120027B1 (ar) 2002-06-03
UA32524C2 (uk) 2001-02-15
GR3026642T3 (en) 1998-07-31
SG48053A1 (en) 1998-04-17
WO1991018895A1 (en) 1991-12-12
IS1752B (is) 2000-07-21
CA2083605A1 (en) 1991-12-08
LV10271B (en) 1995-04-20
RU2061693C1 (ru) 1996-06-10
BG61265B1 (en) 1997-04-30
TNSN91042A1 (fr) 1992-10-25
HU214323B (hu) 1998-03-02
AU640246B2 (en) 1993-08-19
ES2113378T3 (es) 1998-05-01
IL98274A (en) 1995-03-30
CS172691A3 (en) 1992-01-15
MA22171A1 (fr) 1991-12-31
CA2083605C (en) 1998-12-08

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