盐酸考尼伐坦的合成  

Synthesis of Conivaptan Hydrochloride

作　　者：郑登宇 高文磊[1] 赵俊[1] 贾景雨[1] 曹胜华[1] 

机构地区：[1]四川抗菌素工业研究所,四川成都610052

出　　处：《中国医药工业杂志》2015年第9期939-942,共4页Chinese Journal of Pharmaceuticals

摘　　要：2-苯基苯甲酸与对氨基苯甲酸经酰胺化反应得到4-(2-苯基苯甲酰胺基)苯甲酸(12)。同时,氨茴酸甲酯(2)经磺酰化、N-烷基化、分子内缩合关环、酸性条件下脱氰基和溴代得到1-对甲苯磺酰基-4-溴-2,3,4,5-四氢-5-氧代-1H-苯并氮,再与盐酸乙脒缩合并关环形成咪唑环、脱磺酰基得到2-甲基-1,4,5,6-四氢咪唑[4,5-d][1]苯并氮,最后与12通过酰胺化、成盐制得精氨酸加压素拮抗药盐酸考尼伐坦,总收率为25.5%(以2计)。4- [ （1, 1＇-Biphenyl） -2-ylcarboxamido] benzoic acid （12） was prepared from （1, 1＇-biphenyl） -2- carboxylic acid by amidation with 4-aminobenzoic acid. Conivaptan hydrochloride, a arginine vasopressin antagonist, was synthesized from methyl anthranilate （2） via sulfonylation, N-alkylation, intramolecular condensation, decyanation under acidic conditions, and bromination to give 1-tosyl-4-bromo-2,3,4,5-tetrahydro-5-oxo-1H-benzazepine, which was subjected to reaction with acetamidine hydrochloride and detosylation to give 2-methyl-1,4,5,6-tetrahydroimidazo [4,5-d] [1]benzazepine, followed by amidation with 12 and slat formation with an overall yield of 25.5 % （based on compound 2）.

关 键 词：盐酸考尼伐坦 精氨酸加压素拮抗药 合成 

分 类 号：R972.9[医药卫生—药品]