Trimazosin hydrochloride, CP-191061, Supres, Cardovar
(2-羟基-2-甲基丙基)4-(4-氨基-6,7,8-三甲氧基喹唑啉-2-基)哌嗪-1-羧酸酯盐酸盐 三甲哌唑嗪Chemical Name: 4-(4-Amino-6,7,8-trimethoxy-2-quinazolinyl)-1-piperazinecarboxylic acid 2-hydroxy-2-methylpropyl ester monohydrochloride monohydrate
CAS No. 53746-46-6, 35795-17-6 (anhydrous), 35795-16-5 (anhydrous free base)
项目整合开发状态: Withdrawn
项目研究机构: Bristol-Myers Squibb (Originator), Pfizer (Originator)
合成路线:The cyclization of 2-amino-3,4,5-trimethoxybenzoic acid (I) with potassium cyanate in water-acetic acid gives 6,7,8-trimethoxy-2,4-(1H,3H)-quinazolinedione (II),which by refluxing with POCl3 is converted into 6,7,8-trimethoxy-2,4-dichloroquinazoline (III).The reaction of (III) with anhydrous NH3 in THF yields 2-chloro-4-amino-6,7,8-trimethoxyquinazoline (IV),which is then condensed with 2-methylallyl-1-piperazinecarboxylate (V) in refluxing isoamyl alcohol (A) to afford 2-methylallyl-4-(4-amino-6,7,8-trimethoxyquinazolin-2-yl)piperazine-1-carboxylate (VI).Finally,the allyl group of (VI) is hydrated by treating with aqueous sulfuric acid,and converted into the hydrochloride by treatment with ethanolic HCl.
📌 参考资料/链接：
参考文献标题:Trimazosin hydrochloride
文献作者:Castar,J.; Weetman,D.F.
参考来源:Drugs Fut 1978,3(4),325
📄 详细内容
合成路线:The cyclization of 2-amino-3,4,5-trimethoxybenzoic acid (I) with potassium cyanate in water-acetic acid gives 6,7,8-trimethoxy-2,4-(1H,3H)-quinazolinedione (II),which by refluxing with POCl3 is converted into 6,7,8-trimethoxy-2,4-dichloroquinazoline (III).The reaction of (III) with anhydrous NH3 in THF yields 2-chloro-4-amino-6,7,8-trimethoxyquinazoline (IV),which is then condensed with 2-methylallyl-1-piperazinecarboxylate (V) in refluxing isoamyl alcohol (A) to afford 2-methylallyl-4-(4-amino-6,7,8-trimethoxyquinazolin-2-yl)piperazine-1-carboxylate (VI).Finally,the allyl group of (VI) is hydrated by treating with aqueous sulfuric acid,and converted into the hydrochloride by treatment with ethanolic HCl.
参考文献标题:Trialkyloxy quinazolines
文献作者:Hess,H.J.
参考来源:DE 2120495; DE 2167157; FR 2092154; GB 1309835; JP 52068191; US 3669968