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

摘要

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-2H-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-2H-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-2H-benzo[c][1,2,3]triazino[4,5,6-ij][2,7]naphthyridine-1-carbonitriles 16a-c.