Preparation of tetrasubstituted pyrimido[4,5-d]pyrimidine diones

A novel synthetic route to 1,3,5,7-tetrasubstituted pyrimido[4,5-d]pyrimidine-2,4-diones, of interest for potential antitumor activity, is reported. The route uses 1,3-disubstituted 6-amino uracils as starting materials. The key step is a hydrazine-induced cyclization reaction to form the fused pyrimidine ring. By choosing different uracils, acylation reagents, and alkylation reagents, substituents at N-1, N-3, C-5, and C-7 may be selectively varied to provide a structurally diverse set of compounds for biological evaluation. (C) 2015 Published by Elsevier Ltd.