伊贝沙坦的合成  

Synthesis of Irbesartan

作　　者：应佳妮 王兴飞 万浩芳 YING Jia-ni;WANG Xing-fei;WAN Hao-fang(Academy of Chinese Medical Sciences,Zhejiang Chinese Medical University,Hangzhou 310051,China;Zhejiang Lanzhishan Science and Technology Development Co.,Ltd.,Huzhou 313200,China)

机构地区：[1]浙江中医药大学中医药科学院,浙江杭州310051 [2]浙江岚之山科技发展有限公司,浙江湖州313200

出　　处：《合成化学》2021年第3期241-245,共5页Chinese Journal of Synthetic Chemistry

基　　金：浙江省自然科学基金资助项目(LQ20H270017);浙江中医药大学校级科研基金资助项目(2019ZY30)。

摘　　要：以环戊酮为起始原料,与氰胺、戊酰化物反应得到N-(1-氰基环戊基)戊酰胺(2);2经双氧水水解得到1-戊酰胺基环戊烷-1-羟酰胺(3);化合物3依次经分子内环合、酸化和缩合制得4′-[(2-丁基-4-氧-1,3-二氮杂螺环[4,4]壬-1-烯-3-基)甲基]联苯-2-甲腈(5);化合物5与叠氮钠发生叠氮化反应合成了伊贝沙坦(6),总收率40.7%,纯度99.5%,其结构经^(1)H NMR、^(13)C NMR和HR-MS(ESI)确证。Irbesartan has been obtained through six steps from cyclopentanone,which is easily transformed into N-(1-cyanocyclopentyl)pentanamide by reacting with cyanamide and valeryl compound.Treatment of N-(1-cyanocyclopentyl)pentanamide with hydrogen peroxide,followed by intramolecular cyclization,acidification and condensation provided 4′-[(2-butyl-4-oxo-1,3-diazaspiro[4,4]non-1-en-3-yl)methyl]biphenyl-2-carbonitrile(5).Irbesartan was obtained by the azide reaction between compound 5 and sodium azide with total yield of 40.7%and purity of 99.5%.The structure was confirmed by^(1)HNMR,^(13)CNMR and HR-MS(ESI).

关 键 词：环戊酮 氰胺 水解 环合 伊贝沙坦 合成 

分 类 号：O625.42[理学—有机化学] R914.5[理学—化学]