Naphthyridines part 4: unprecedented synthesis of polyfunctionally substituted benzo[c][2,7]naphthyridines and benzo[c]pyrimido[4,5,6-ij][2,7]naphthyridines with structural analogy to pyrido[4,3,2-mn]acridines present in the marine tetracyclic pyridoacridine alkaloids

An easy, efficient and one-step synthesis of the versatile, hitherto unreported of polyfunctionally substituted benzo[ c ][2,7]naphthyridines 4a–c is described. The reaction of 4a–c with sodium azide gives the corresponding tetracyclic ring system 6a–c in near quantitative yield, and with phenyl isothiocyanate it gives the corresponding novel 3-alkyl-2-oxo-6-phenyl-5-thioxo-3,4,5,6-tetrahydro-2 H -benzo[ c ]pyrimido[4,5,6- ij ][2,7]naphthyridine-1-carbonitriles 8a–c . Refluxing compound 4a , with alkyl amines 9a–d for 2–3 h furnished 3-alkyl-5-alkylamino-4-amino-2-oxo-2,3-dihydrobenzo[ c ][2,7]naphthyridine-1-carbonitriles 10a–d , as stable crystalline solids. Compounds 10a–d reacted with acetic anhydride and triethyl orthoformate to furnish novel 3,6-dialkyl-2-oxo-3,6-dihydro-2 H -benzo[ c ]-pyrimido[4,5,6- ij ][2,7]naphthyridine-1-carbonitriles 13a–c and 14a–c , respectively. Lastly, diazotization of 10a–c afforded the novel tetracyclic ring system 3,6-dialkyl-2-oxo-3,6-dihydro-2 H -benzo[ c ][1,2,3]triazino[4,5,6- ij ][2,7]naphthyridine-1-carbonitriles 16a–c .