盐酸特拉唑嗪杂质的合成

Synthesis of impurities of terazosin hydrochloride

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.