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 iminophosphorane derivative 5, and subsequent hydrolysis (Staudinger reaction) gave 6-amino-2pyridone 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 Na 2 S 2 O 4 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.