Scalable, Chromatography-Free Synthesis of 1,7-dimethylxanthine

Abstract

: 1,7-dimethylxanthine is a critical intermediate in the pharmaceutical industry. In this paper, a scalable route for the synthesis of 1,7-dimethylxanthine was developed. The method in-cluded two steps: (1) acylation reaction of ethyl 4-amino-1-methyl-1H-imidazole-5- carboxylate was carried out by using commercially available methylcarbamoyl chloride as the starting materi-al; (2) through cyclization of pyrimidine ring with aqueous sodium hydroxide, 1,7-dimethylxanthine was obtained with a total yield of 80%, and its HPLC purity was 99% by area. The method is very efficient and readily adaptable to kilogram scale, and because of the cycliza-tion reaction process in aqueous conditions, this route is worthy of exploration for industrial ap-plication. result: 1, 7-dimethylxanthine was prepared with an overall yield of 80% with an HPLC purity of 99% by area. conclusion: We developed a new synthetic route for making 1, 7-dimethyl xanthine with high yield. The method uses commercially available raw materials to synthesize 1, 7-dimethyl xanthine on kilogram scale. Because of higher yield, higher purity and completion of cyclization reaction in aqueous condition, it was robustness, lower cost, and small environment impact. This route is worthy of exploration for industrial application.