盐酸阿呋唑嗪合成工艺改进  

Improved synthesis of alfuzosin hydrochloride

作　　者：朱星研[1] 王岩岩[1] 邸岩[1] 姜芳[1] 许佑君[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2009年第5期352-355,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的合成盐酸阿呋唑嗪并优化其工艺。方法以藜芦酸为原料,其甲酯经混酸硝化后,在Lewis酸氯化铵溶液存在下经Fe粉还原,再依次经尿素环合、三氯氧磷氯代和氨水氨解,得到关键中间体2-氯-4-氨基-6,7-二甲氧基喹唑啉(6)。化合物6与3-甲氨基丙腈缩合,经Raney Ni-H2催化还原得N-甲基-N-(4-氨基-6,7-二甲氧基-2-喹唑啉基)-1,3-丙二胺(8),8与2-四氢呋喃甲酸缩合后再与盐酸成盐,制得目标物盐酸阿呋唑嗪。结果与结论目标化合物的结构经MS、1H-NMR谱确证。该工艺路线操作简单,总收率由文献的7.8%提高到25.9%。Aim To improve the synthesis of alfuzosin hydrochloride and to optimize its process.Methods The key intermediate,2-chloro-4-amino-6,7-dimethoxyquinazoline（6）,was obtained from methyl ester of veratryl acid via nitration,reduction by powdered-Fe in the presence of aqueous NH4Cl,cyclization with urea,chlorination with phosphorus oxychloride and eventually aminolysis with aqueous ammonia.Compound 6 reacted with 3-methyl aminopropionitrile followed by the catalytic reduction of the nitrile with Raney Ni-H2 to afford the desired amine N2-（3-aminopropyl）-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine（8）.8 was condensed with 2-tetrahydrofuroic acid and then treated with hydrogen chloride in methanol to give the target in hydrochloride form.Results and conclusion The structure of target compound was confirmed by MS and 1H-NMR.The total yield was increased from 7.8% reported by literature to 25.9% by simplifying the process of the route.

关 键 词：盐酸阿呋唑嗪 良性前列腺增生 工艺改进 

分 类 号：TQ463.53[化学工程—制药化工]