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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。
Objective To improve the quality control of the alpha-blocker anti-hypertensive drug terazosin hydrochloride, three specific impurities of terazosin hydrochloride were synthesized. Methods Terazosin hydrochloride was used as starting material to prepare 1- (4-hydroxy-6,7-dimethoxy-2-quinazolinyl) -4 - [(tetrahydrofuranyl) (Impurity B); Terazosin hydrochloride as a starting material, hydrolysis to give 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) (Impurity C); 2-chloro-4-amino-6,7-dimethoxyquinazoline as a starting material, N- Amino-6,7-dimethoxy-2-quinazolinyl) piperazine dihydrochloride (Impurity E). RESULTS AND CONCLUSIONS The structures of the three impurities were confirmed by 1H-NMR and MS, and their purity was comparable to or better than that of the USP. It could be used as reference substance for quality control of terazosin hydrochloride APIs.