1,8-Naphthyridines II: synthesis of novel polyfunctionally substituted 1,8-naphthyridinones and their degradation to 6-aminopyridones

Reaction of 6-chloro-3-cyano-5-formyl-1,4-dimethyl-(1H)-pyridin-2-one (1) with [(ethoxycarbonyl) methylene] triphenylphosphorane (2) afforded 5-ethoxycarbonylvinyl-2-pyridone derivative 3 Azidation of 3 yielded 6-azido-2-pyridone derivative 4, in excellent yield. Refluxing 4 with one equivalent of triphenylphosphine (aza-Wittig reaction) gave imino-phosphorane derivative 5, and subsequent hydrolysis (Staudinger reaction) gave 6-amino-2-pyridone 6. When aminopyridone 6 was refluxed in 1,2-dichlorobenzene it cyclised to the novel 1,8-naphthyridin-2-one 7. Reaction of compound 1 with malononitrile in an ethanolic solution containing TEA afforded 6-chloropyridone derivative 18, which reacted with sodium azide to furnish the corresponding azido compound 19. Reduction of 19 with Na2S2O4 did not give the corresponding aminopyridone 20 but rather the interesting 1,8-naphthyridin-2(1H)-ones 21. Alternatively, compound 21 could also be obtained by refluxing aminopyridone 9 with malononitrile in an ethanolic solution containing TEA. On the other hand, reacting 9 with phenacylcyanide, under the same reaction conditions as used for the synthesis of 21, did not afford the new 1,8-naphthyridine-2-one 22, but rather 6-amino-3-cyano-1,4-dimethyl-(1H)-pyridine-2-one (23), via the thermal degradation of the intermediate 22.