The Improved Synthesis Of Alfuzosin Hydrochloride

Alfuzosin hydrochloride (1), an-adrenergic receptor antagonist, has been widely used for the treatment of benign prostatic hyperplasia all over the world.The pathogenesis of benign prostatic hyperplasia was summarized in this thesis. Here also introduced the commonly used treatment of benign prostatic hyperplasia, and reviewed the progress in the drug research and development of the type in recent years.According to the reported methods, the key intermediate 2 was obtained in this paper from the methyl ester of veratryl acid via nitration, powdered-Fe reduction, cyclization with urea, chlorination with phosphorus oxychloride and eventually aminolysis with aqueous ammonia. Compound 2 was reacted with 3-methylaminopropionitrile followed by the reduction of the nitrile with Raney Ni/H2 to afford the required amine 23.23 was condensed with 2-tetrahydrofuroic acid and treated with hydrogen chloride in methanol to give the target in salt form. The overall yield of our improved synthesis was 26.8%.The reduction compound 7 to give 8 and its work-up procedure was intensive studied in this paper, and it was found that the reaction could be carried out by powered-Fe reduction in the presence of the mild Lewis acid, aq. NH4Cl. After the removal of the reaction solvent, the mixture was diluted with dichloromethane, and charcoal was added for the help of easy filtration, at last the mixture could be freely filtered through a short pad for further work-up procedure. In addition, instead of ammonia gas, aqueous ammonia was used for the amination of the key intermediate 2, the yield had been significantly improved in this thesis.