Abstract: OBJECTIVE To study the synthetic route of penciclovir, a kind of new antiviral drug, was synthesized with methyl 4-bromo-2, 2-bis-methoxycarbonyl-butyrate as raw material. METHODS Target compound was synthesized by means of the regioselective alkylation of 2-amino-6-chloropurine as a pivotal step, followed by decarboxylation, reduction, acetylation, and hydrolysis without separation of the products. RESULTS The total yield was amount to 33%, higher than literature. The target molecule was confirmed by MS, elementary analysis, 1H-NMR and 13C-NMR. CONCLUSION The improved process can be easily operated and is suitable for a scale production.