盐酸特拉唑嗪杂质的合成  

Synthesis of impurities of terazosin hydrochloride

作　　者：武红娜 李波[1] 张文轩[1] 吴松[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所活性物质发现与适药化研究北京市重点实验室,北京100050

出　　处：《中国药物化学杂志》2015年第6期446-449,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家"十二五"重大新药创制科技重大专项(2013ZX09402103)

摘　　要：目的为了加强对α受体阻滞剂类抗高血压药盐酸特拉唑嗪原料药的质量控制,合成了盐酸特拉唑嗪的3个特定杂质。方法以盐酸特拉唑嗪为原料,经重氮化、水解反应制得1-(4-羟基-6,7-二甲氧基-2-喹唑啉基)-4-[(四氢呋喃基)碳酰基]-哌嗪(杂质B);以盐酸特拉唑嗪为起始原料,经水解制得1-(4-氨基-6,7-二甲氧基-2-喹唑啉基)哌嗪二盐酸盐(杂质C);以2-氯-4-氨基-6,7-二甲氧基喹唑啉为起始原料,经N-取代反应制得1,4-二(4-氨基-6,7-二甲氧基-2-喹唑啉基)哌嗪二盐酸盐(杂质E)。结果与结论合成的3种杂质的结构经1H-NMR、MS确证,纯度相当或优于美国药典杂质对照品,可以作为盐酸特拉唑嗪原料药质量控制的杂质对照品。In order to perform the quality control of alphal-adrenoceptor blockers antihypertensive drug tera- zosin hydrochloride, three impurities were synthesized. Impurity B, 1-（ 4-hydroxy-6,7-dimethoxy-2-quin- azolinyl） -4-[ （tetrahydrofuranyl） carbonyl ] piperazine was synthesized by diazo reaction followed by hydro- lysis from terazosin hydrochloride. Impurity C, 1-（4-amino-6, 7-dimethyl-2-quinazolinyl ）piperazine- dihydrochloride was prepared by hydrolysis of terazosin hydrochloride. And impurity E, 1,4-bis（4-amino-6, 7-dimethoxy-2-quinazolinyl） piperazine dihydrochloride was synthesized by N-substitution reaction from 2- chloro-4-amino-6,7-dimethoxy quinazoline. The structures were confirmed by MS and 1H-NMR. Their puri- fies were fairly with or better than USP impurity standard substances, and they can be used as the standard substances in the quality control of terazosin hydrochloride.

关 键 词：盐酸特拉唑嗪 杂质 合成 

分 类 号：R914[医药卫生—药物化学]