An efficient synthesis of 7,8-dihydropyrimido[5,4-d]pyrimidines

Article abstract of DOI:10.1002/ejoc.200600883

7,8-Dihydropyrimido[5,4-d]pyrimidines 4 were isolated in very good yields by treatment of 9-aryl-6-cyanopurines 1 with primary amines. Nucleophilic attack of the amine on C8 of the purine ring was followed by ring-opening of the imidazole unit, and subsequent intramolecular cyclization involving the newly formed amidine group and the cyano substituent in the pyrimidine ring produced the 7,8-dihydropyrimido[5,4-d]pyrimidine structure 4. When ammonia was used instead of primary amines, compound 4 rapidly reacted further to afford the more stable pyrimido[5,4-d]pyrimidine 6 as a result of tautomeric equilibration. The aromatic structure 6 was also isolated when purine 1a and an excess of ethanolamine were heated at reflux in methanol, and also when purine 1c was combined with an excess of (4-methoxyphenyl)-hydrazine in THF at room temperature in the presence of a catalytic amount of DBU. In both cases the product is formed by a Dimroth rearrangement of the precursor 7,8-dihydropyrimido[5,4-d]pyrimidine 4. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.