文献类型：期刊文献

英文题名：Synthesis of a novel angiotensin II receptor antagonist olmesartan medoxomil

作者：Yu, Xin-Hong; Tang, Jian; Wen, Xin-Min; Mao, Qing-Hua; Shen, Yong-Jia

机构：[1] School of Chemistry and Pharmaceutics, East China University of Science and Technology, Shanghai 200237, China

年份：2005

卷号：31

期号：2

起止页码：189

外文期刊名：Huadong Ligong Daxue Xuebao /Journal of East China University of Science and Technology

收录：EI(收录号：2005209110089)

语种：英文

摘要：A new angiotensin I receptor antagonist, (5-methyl-2-oxo-1,3-dioxol-4-yl) methyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2'-1H-tetrazol-5-yl- biphenyl-4-yl) methyl] imdazole-5-carboxylate (Olmesartan medoxomil), was synthesized using tartaric acid as starting material via nitration, cyclization, esterifcation, Grignard reaction, N-alkylation, hydrolyzation, O-alkylation and N-deprotection in 32.7% overall yield. The structure of title compound has been characterized by MS (mass spectrum), 1H-NMR (nuclear magnetic resonance) and IR (infrared spectrum). The condensation of 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester with 5-[4'-(bromomethyl) biphenyl-2-yl]-1-(triphenylmethyl) tetrazole by means of potassium hydroxide in DMF, instead of potassium tert-butoxide in dimethylacetamide or sodium hydroxide in DMF, gives the corresponding N-alkylated product, which is hydrolyzed with sodium hydroxide, instead of lithium hydroxide, in dioxane-water to the desired acid. The improved process is more practical.