A SIMPLE AND ECONOMICAL PROCEDURE FOR SYNTHESIS OF AMANTADINE HYDROCHLORIDE

摘要

Amantadine hydrochloride (1), a well-known antiviral drug, has been used to treat certain type-A influenza infections and been also medicated as an anti-dyskinetic agent for Parkinson’s disease. In this paper, we report a simple and economical procedure for synthesis of amantadine hydrochloride (1) from 1-bromoadamantane (3) and urea in a one-step procedure with high yield (81%) and advantage. The structure of the obtained amantadine hydrochloride was confirmed by MS, sup1/supH-NMR and sup13/supC-NMR spectra and its quality was validated following the United State Pharmacopeia (USP 38). In addition, the synthesis condition was optimized following parameters including reaction reagent as source of nitrogen, reaction temperature, reaction time, reagent molar-ratio, solvent and HCl concentration, successively, to archive the highest yield of amantadine hydrochloride (1) at the following certified condition: reaction temperature = 175°C; reaction time = 1.0 h; molar ratio of (urea: 1-bromo-adamantane) = (3 : 1), in diphenyl ether with ratio of (Ad-Br : Phsub2/subO) = 1.1 g :1 mL), respectively.