降血压药物替米沙坦的合成.pdfVIP

Chinese Journal ofN ew Drugs 2010, 19( 18) 1 1 2 1 , , , ( 1华东理工大学化学与分子工程学院, 上海 200237; 2 上海应用技术学院, 上海 20023 ) [] : 合成替米沙坦, 并对其工艺进行改进: 3甲基4氨基苯甲酸为起始原料, 经酯 化酰化硝化还原环合水解得 2正丙基4甲基6羧基苯并咪唑, 在多聚磷酸作用下与N甲基邻苯二胺 缩合后的产物, 再与 2氰基4溴甲基联苯反应, 水解后即得替米沙坦: 目标产物的成本降低, 反应条件温和, 适合于工业化生产 [] 降血压药; 替米沙坦; 合成 [] R972. 4 [] A [] 1003- 3734( 2010) 18- 1726- 03 Synthesis of the antihypertensive drug telm isartan 1 1 2 1 X IAO Shijun , YANG Xueyan , WU Fanhong, WANG Fei ( 1School of Chem istry and Molecular Eng ineering, East China University of Science and Technology, Shanghai 200237, China; 2 Shanghai Institute of Technology, Shanghai 20023 , China) [Abstract] Objective: To synthesize telm isartan, and then optmi ize its process. Methods: U sing 3meth yl4am inobenzonic acid as the starting material, 2npropyl4methyl6carboxy benzmi idazole w as synthesized via esterification, acylation, nitration, reduction, cyclization and hydrolysis. Th is compound w as condensed w ithN methylophenylened iam ine in polyphosphoric acid, and the product then reacted w ith 2cyano4bromomethylb i phenyl to produce telm isartan after hydrolysis. Results and Conclusion: The target compound is obtained under m ild reaction condition w ith low er cost, wh ich is su itable for largescale production. [Key ords] antihypertensive drug; telm isartan; synthesis 4[ 246 4, 4 Pd/C ( 12)1] 5, 5 6, 6, 2, , N 1 0 ! 20 h , 7, 7 42 , , , , 20. 9% [ 4] , 2 , , 1, [ - 8]N aOH ,