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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 synthesize alfuzosin hydrochloride and optimize its process. The method takes veratronic acid as raw material, and the methyl ester is nitrated by mixed acid, and then is reduced by Fe powder in the presence of Lewis acid ammonium chloride solution, followed by urea cyclization, chlorination with phosphorous oxychloride and ammonia to obtain the key The intermediate 2-chloro-4-amino-6,7-dimethoxyquinazoline (6). Compound 6 was condensed with 3-methylaminopropionitrile and catalytically reduced by Raney Ni-H2 to give N-methyl-N- (4-amino-6,7-dimethoxy-2- quinazolinyl) 3-propanediamine (8), 8 and 2-tetrahydrofuran-carboxylic acid and then salified with hydrochloric acid to obtain the target alfuzosin hydrochloride. Results and Conclusion The structures of the target compounds were confirmed by MS and 1H-NMR. The process route is simple and the total yield is increased from 7.8% in the literature to 25.9%.