Synthetic utility of a heterocyclic o-aminoaldehyde: synthesis of pyrazolopyridopyrimidines, pyrazolonaphthyridines, and pyrazolopyrimidonaphthyridinones

A series of various polysubstituted pyrazolo[3,4- h ][1,6]naphthyridines, benzo[ b ]pyrazolo[3,4- h ][1,6]naphthyridines, and pyrazolo[4′,3′:5,6]pyrido[4,3- d ]pyrimidines were synthesized by Friedländer condensation of 4-amino-3-methyl-1-phenyl-1 H -pyrazolo[3,4- b ]pyridine-5-carbaldehyde ( o -aminoaldehyde) with active methylene compounds. The o -aminoaldehyde was functionalized to o -aminonitrile and o -aminocarboxamide with malononitrile and cyanoacetamide, respectively, which on condensation with monosubstituted ureas and acetic anhydride, respectively, afforded pyrazolo[3,4- h ]pyrimido[4,5- b ][1,6]naphthyridines. Graphical abstract