Synthesis and regioselective N- and O-alkylation of 1H- or 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5,7(4H,6H)-diones (8-azaxanthines) and transformation of their 3-alkyl derivatives into 1-alkyl isomers

Several alkylating agents, for example alkyl halides and dimethyl sulfate, were employed in aprotic Solvents Under a variety of conditions for the alkylation of mono- and disubstituted 1H- or 3H-[1,2,3]triazolo[4,5-d]pyrimidine-5,7(4H,6H)-diones, which were prepared by cyclization of the appropriate 5,6-diaminouracils with nitrous acid. The alkylation on the triazole ring in the presence of anhydrous potassium carbonate took place simultaneously at the 1- and 2-positions, with alkylation at the 2-position taking priority. Similar alkylation on the pyrimidine ring with an equivalent alkylating reagent took place only at the 4-position. The alkylation of 3,6-disubstituted derivatives at room temperature led to 5-O-alkylation accompanied by 4-N-alkylation, but at high temperature only 4-N-alkylation took place. Reaction of 3,4,6-trisubstituted derivatives with excess alkylating agent at high temperature leads to the formation of 1,4,6-trisubstituted derivatives with elimination of the 3-substituent.

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This is a author's copy,as published in Synthesis-Stuttgart , 2006 Issue.24 pp.4167-4179
Publisher URL: http://dx.doi.org/10.1055/s-2006-950337
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