Novel 6-substituted Pyrimidines and Pyrimido[5,4-d]pyrimidines from (2-acetamido-1,2-dicyanovinyl)Ammonium Chloride

The reaction of triethyl orthoformate with 5-amino-6-ethoxy-2-methyl-4-pyrimidinecarbonitrile (5), available from DAMN via the ammonium salt 4, afforded iminoformate 6. The latter cyclised with aqueous ammonia or equimolar amounts of aryl/benzyl amines to give the corresponding pyrimido[5,4-d]pyrimidines 8, 9a–c. Reaction with excess of aqueous ethylamine, methylamine or benzylamine caused cyclisation with substitution of an ethoxy group to give 9d–f. Hydrolysis of compounds 8, 9a–b under acidic conditions gave the corresponding pyrimido[5,4-d]pyrimidones 10, 11a–b. Heating 4 to reflux in THF unexpectedly formed 5-amino-6-(4-chlorobutoxy)-2-methyl-4-pyrimidinecarbonitrile (12) and 5-amino-2-methyl-6-oxo-1,6-dihydro-4-pyrimidinecarbonitrile (13). X-Ray crystallography established the structure of N-ethyl-N-(7-ethyl-8-imino-2-methyl-7,8-dihydropyrimido[5,4-d]pyrimid in-4-yl)amine (9e).