专利号:US-8173817-B2 优先权日:2004-05-28 标 题 :Stereoselective synthesis of benzimidazole sulfoxides 发明人:REDDY BANDI PARTHASARADHI; REDDY KURA RATHNAKAR; REDDY RAPOLU RAJI; REDDY DASARI MURALIDHARA 权利人:REDDY BANDI PARTHASARADHI; REDDY KURA RATHNAKAR; REDDY RAPOLU RAJI; REDDY DASARI MURALIDHARA; HETERO DRUGS LTD 摘要:The present invention relates to a process for stereoselective synthesis of substituted sulfoxides either as a single enantiomer or in an enantiomerically enriched form. Thus, 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]thio]-1H-benzimidazole is reacted with (R)-camphorsulfonyl chloride to form a mixture of 1-(R)-camphorsulfonyl-5- (and 6-)methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methylthio]-1H-benzimidazole, oxidized to obtain a diastereomeric excess of 1-(R)-camphorsulfonyl-(5- and 6-)-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl-(S)-sulfinyl]-1H-benzimidazole over 1-(R)-camphorsulfonyl-(5- and 6-)-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl-(R)-sulfinyl]-1H-benzimidazole, the diastereomers are separated by fractional crystallization and the separated 1-(R)-camphorsulfonyl-(5- and 6-)-methoxy-2-[(3,5-dimethyl-4-methoxy-2-pyridyl)methyl-(S)-sulfinyl]-1H-benzimidazole is deprotected to give esomeprazole.
专利号:US-5386032-A 优先权日:1990-06-07 标 题 :Method of synthesis of 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl-1H-benzimidazole (omeprazole) 发明人:BRAENDSTROEM ARNE E 权利人:ASTRA AB 摘要:The present invention relates to an improved method for the synthesis of omeprazole, comprising the steps of reacting 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-1H-benzimidazole with m-chloroperoxybenzoic acid in a methylene chloride solution at a substantially constant pH of about 8.0 to 8.6; extracting the reaction mixture with aqueous NaOH; separating the aqueous phase from the organic phase; and adding an alkyl formate to the aqueous phase, resulting in crystallization of omeprazole.
专利号:US-6268502-B1 优先权日:1998-07-13 标 题 :Process of synthesis of 5-methoxy- 2-[(4-methoxy-3,5-dimethy-2-pyridyl)methyl]sulfiny-1h-benzimidazole 发明人:HAFNER MILAC NATASA; JEREB DARJA 权利人:LEK TOVARNA FARMACEVTSKIH 摘要:An improved process of synthesis of 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl-1H-benzimidazole (omeprazole) by oxidation of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]benzimidazole with 3-chloroperoxy-benzoic acid in ethyl acetate wherein omeprazole is poorly soluble, at a temperature between -10° C. and 5° C. is disclosed. The second step is a purification of the crude product by dissolution and reprecipitation of the final product.
专利号:US-5627295-A 优先权日:1993-03-19 标 题 :Synthesis of higher alcohols 发明人:SOFIANOS ALKEOS; SCURRELL MICHAEL S 权利人:PATLICO INTERNATIONAL BV 摘要:A higher alcohol synthesis catalyst precursor comprises a homogeneous, highly crystalline, hydroxycarbonate compound containing copper, zinc and at least one element selected from the group consisting of aluminium, manganese and chromium. It also comprises at least one element from at least one of the followng groups of the Periodic Table of Elements: Group IIIA, Group IIIB, Group IVB and Group VIIB.
专利号:US-6437139-B1 优先权日:1997-05-06 标题 :Synthesis of pharmaceutically useful pyridine derivatives 发明人:ZOGHBI MICHEL; CHEN LIQUIN 权利人:PDI RES LAB INC 摘要:A process is provided for the preparation of compounds of formula I,useful in the preparation of compounds such as Omeprazole, Lansoprazole and Pantoprazole, wherein R1=H or CH3, R2=H or CH3, R3=Alkoxy (1-4C), OCH2CF3, Cyano, Hydrogen, Halogen, Acetoxy or Aryloxy, any electron withdrawing group or salts (organic or inorganic) of electron donating groups, R=Alkoxy, Hydroxy, Halogen, Activated ester, Tosylate, Mesylate, Thiol or Xanthyl, wherein the process for the preparation of compound of formula I employs a free radical reaction to functionalize the 2-position.
专利号:US-7683178-B2 优先权日:2002-10-18 标 题 :Method for the synthesis of a benzimidazole compound 发明人:GUSTAVSSON ANDERS 权利人:ASTRAZENECA AB 摘要:A process for the manufacture of omeprazole or esomeprazole from pyrmethyl alcohol via pyrmethyl chloride and pyrmetazole characterized in that the whole reaction sequence is carried out without any isolation or purification of intermediates. Further, the reaction is carried out in a solvent system common for the whole reaction sequence and inert to the reactants formed during the process and used in the process and comprises a water immiscible organic solvent and a specified amount of water.
参考标题:Synthesis Of Benzyl Bromides With Hexabromoacetone: An Alternative Path To Drug Intermediates 作者:Kara M. Joseph,Isabel Larraza-Sanchez |发布日期:2011.1 摘要:Low Temperatures And Under Neutral Conditions. The Present Protocol Was Applied To The Heterocyclic Analogues And To The Successful Synthesis Of The Precursor Of The Antiulcer Drug Omeprazole, Thus Furnishing An Alternate, Mild Method For The Preparation Of These Drug Intermediates. A Significant Steric Factor Was Observed Throughout Both Series Supporting A Sn2 Mechanism.
合成参考文献
摘要:Lattanzi, A., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 976. 摘要:Winkler, C. K.; Faber, K.; Kroutil, W., Science of Synthesis, (2022) , 5. 参考文献:10.1016/s0022-3565(25)38797-5 摘要:Fryklund J, Wallmark B. Sulfide and sulfoxide derivatives of substituted benzimidazoles inhibit acid formation in isolated gastric glands by different mechanisms. The Journal of Pharmacology and Experimental Therapeutics. 1986 Jan;236(1):248–53. doi: 10.1016/s0022-3565(25)38797-5. 参考文献:10.1016/j.jchromb.2006.07.047 摘要:Rezk NL, Brown KC, Kashuba AD. A simple and sensitive bioanalytical assay for simultaneous determination of omeprazole and its three major metabolites in human blood plasma using RP-HPLC after a simple liquid-liquid extraction procedure. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Dec 05;844(2):314–21. doi: 10.1016/j.jchromb.2006.07.047.