Synthesis of paraxanthine and isoparaxanthine analogs (1,7- and 1,9-substituted xanthine derivatives)

摘要

A general, convenient method for the preparation of 1,7- and 1,9-disubstituted xanthine derivatives (paraxanthine and isoparaxanthine analogs) was developed starting from 6-amino-2-methoxypyrimidin-4-one. Alkylation with alkyl halides in acetone/potassium carbonate in the presence of a phase-transfer catalyst (PTC) yielded an equimolar mixture of N3- and O-4-alkylated products, which could be separated by dry column chromatography. The N3-alkylated uracil derivatives were converted to the corresponding 1-alkyl-2-methoxypurin-6-ones by standard procedures. PTC alkylation yielded an equimolar mixture of 7- and 9-alkylated isomers, which were again conveniently separated by dry column chromatography. The title compounds were obtained after acid hydrolysis of the 2-methoxy group in satisfactory yields. [References: 44]