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Letters in Organic Chemistry

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ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

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Research Article

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

Author(s): Shaoguang Sun*, Yucheng Jiang, Hui Mao and Shuya Cui*

Volume 21, Issue 6, 2024

Published on: 22 January, 2024

Page: [530 - 533] Pages: 4

DOI: 10.2174/0115701786269449231116062157

Price: $65

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 included 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 material; (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 cyclization reaction process in aqueous conditions, this route is worthy of exploration for industrial application.

Keywords: 1, 7-dimethylxanthine, acylation reaction, cyclization, phosphodiesterase, scalable, chromatography.

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