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.
出处
《中国药物化学杂志》
CAS
CSCD
2009年第5期352-355,共4页
Chinese Journal of Medicinal Chemistry
关键词
盐酸阿呋唑嗪
良性前列腺增生
工艺改进
alfuzosin hydrochloride benign prostatic hyperplasia process improvement
