缬沙坦的合成  

Synthesis of Valsartan

作　　者：王晓东 郭晔堃[2] 潘璐 黄素萍 

机构地区：[1]常州四药制药有限公司,江苏常州213004 [2]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海200437

出　　处：《中国医药工业杂志》2012年第6期416-418,共3页Chinese Journal of Pharmaceuticals

摘　　要：N-[(2'-氰基联苯-4-基)甲基]-L-缬氨酸甲酯,与正戊酰氯在甲苯中,以DMAP作催化剂、碳酸钠作缚酸剂进行酰化反应制得N-(1-氧代戊基)-N-[(2'-氰基联苯-4-基)甲基]-L-缬氨酸甲酯,再在相转移催化剂双三甲基硅烷化聚乙二醇400(4)作用下与叠氮钠反应成四唑后,经水解制得抗高血压药缬沙坦,总收率约75%。Valsartan was synthesized from N-[（2＇-cyanobiphenyl-4-yl）methyl]-L-valine methyl ester by acylation with n-pentanoyl chloride in toluene with DMAP as catalyst and Na2CO3 as base to give N-（1-oxopentyl）-N-[（2＇-cyanobiphenyl-4-yl）methyl]-L-valine methyl ester,which was subjected to reaction with sodium azide with Bis（trimethylsilyl）-PEG 400（4） as PTC to form the tetrazole,followed by hydrolysis with an overall yield of about 75%.

关 键 词：缬沙坦 抗高血压药 合成 

分 类 号：TQ460.72[医药卫生—药物分析学]