SYNTHESIS OF PARAXANTHINE AND ISOPARAXANTHINE ANALOGS (1,7-SUBSTITUTED AND 1,9-SUBSTITUTED XANTHINE DERIVATIVES)

A general, convenient method for the preparation of 1,7- and 1,9-disub stituted xanthine derivatives (paraxanthine and isoparaxanthine analog s) was developed starting from 6-amino-2-methoxypyrimidin-4-one. Alkyl ation with alkyl halides in acetone/potassium carbonate in the presenc e of a phase-transfer catalyst (PTC) yielded an equimolar mixture of N 3- 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 is omers, which were again conveniently separated by dry column chromatog raphy. The title compounds were obtained after acid hydrolysis of the 2-methoxy group in satisfactory yields.