- Preparation method of lansoprazole key intermediate
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The invention relates to a preparation method of a lansoprazole key intermediate. According to the technical scheme, the preparation method comprises the following steps: firstly, respectively preparing (2, 2, 2-trifluoroethoxy)ethylene (a compound 7) and 3-amino-4-chloro-2-methylbut-2-enoic acid ethyl ester (a compound 9); and then reacting the compound 7 with the compound 9 to prepare 6-(chloromethyl)-5-methyl-4-(2, 2, 2-trifluoroethoxy)-2,3,4,5- tetrahydropyridine; finally, oxidizing 6-(chloromethyl)-5-methyl-4-(2, 2, 2-trifluoroethoxy)-2, 3, 4, 5-tetrahydropyridine (compound 10) by hydrogen peroxide under the catalytic action of Mn(O)-Salon to generate 2-(chloromethyl)-3-methyl-4-(2, 2, 2-trifluoroethoxy)pyridine (compound 5). According to the technical scheme, danger is reduced, energy consumption is reduced, and the method is more suitable for large-scale industrial production.
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Paragraph 0033; 0036; 0037; 0040; 0041; 0044; 0045; 0048
(2020/07/13)
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- Preparation method for dexlansoprazole
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The invention discloses a preparation method for dexlansoprazole, belonging to the field of organic synthesis. The method comprises the following steps: (1) carrying out reaction on 2-hydroxymethyl-3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine and thionyl chloride, and compounding 2-chloromethyl-3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine; (2) putting 2-chloromethyl-3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine acquired in the step (1) and 2-sulfydryl-1H-benzimidazole into an aqueous liquid, and then adding a phase transfer catalyst and sodium hydroxide, thereby acquiring 2-[[3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine-2-group] methylmercapto]-1H-benzimidazole; (3) taking L-ethyl tartrate as a chiral assistant agent, titanium isopropoxide and diisopropylethylamine as a catalyst and cumyl hydroperoxide as an oxidizing agent and reacting with 2-[[3-methyl-4-(2,2,2-trifluoro ethyoxyl) pyridine-2-group] methylmercapto]-1H-benzimidazole acquired in the step (2) at low temperature, thereby acquiring dexlansoprazole. The preparation method for dexlansoprazole disclosed by the invention is simple and efficient, is capable of obviously shortening the reaction time under the condition of guaranteeing the product yield and is capable of improving the product quality.
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Paragraph 0025; 0029; 0030
(2017/08/28)
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- A practical one pot synthesis of 2-[2-(pridylmethyl)-thio]-1H-benzimidazoles
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A combination of Et3N and pTSCl was found to be far superior than pTSCl or benzene sulfonyl chloride alone in convert ing substituted 2-picoline-N-oxides to the corresponding 2-chloromethylpyridines and has been exploited for the synthesis of a variety of 2-[2-(pyridylmethyl)-thio]-1H-benzimidazoles, key intermediates in the manufacture of H+/K+-ATPase inhibitors in a single pot.
- Rane,Pathak,Kaushik,Prasad Rao,Kumar, Ashok
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p. 1211 - 1217
(2007/10/03)
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- 2--1H-thienoimidazoles. A Novel Class of Gastric H+/K+-ATPase Inhibitors
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2-thienoimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K+-ATPase.The isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo.Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with additional electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thienoimidazole lead to highly active compounds with a favorable chemical stability.Various substitution patterns in the thienoimidazole moiety result in lower biological activity.The heptafluorobutyloxy derivative saviprazole (HOE 731, 5d) was selected for further development and is currently undergoing clinical evaluation.Comprehensive pharmacological studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K+-ATPase blocker introduced on the market.
- Weidmann, Klaus,Herling, Andreas W.,Lang, Hans-Jochen,Scheunemann, Karl-Heinz,Rippel, Robert,et al.
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p. 438 - 450
(2007/10/02)
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