Synthesis of 4-substituted pyrimido [5,4-C] cinnoline derivatives

Reaction of 4-aminocinnoline-3-carboxamide or its 8-methyl derivative 1a, b with triethyl orthoformate and acetic anhydride gave rise to the corresponding pyrimido[5,4-c]cinnolin-3H-4-ones 2a-d. 2-Methylpyrimido derivatives 2c,d could also be obtained via ammonolysis of 2-methyl-1,3-oxazino[5,4-c] cinnolin-4-ones 4a,b. On the other hand, reaction of 1a,b with araldehydes afforded 2-arylpyrimidocinnolines 5a-e. Reacting compounds 2a-d with hydrazine and different amines produced the corresponding 4-substituted amino or hydrazino derivatives 7-9. This revealed the reactivity of the 4-position of 2 towards nucleophilic substitution. Attempts to cyclize 7a-d to triazolopyrimidocinnolines are discussed