Collect. Czech. Chem. Commun. 1991, 56, 2420-2429

Synthesis of some 1-alkyl-1,4-dihydro-4-oxo-1,7-naphthyridine-3-carboxylic acids

Stanislav Rádla and Pavel Hradilb

a Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3
b Chemopharma, 400 51 Ústí nad Labem


Reaction of substituted 2-aminopyridines IIIa, IIIb, IIIe, and IIIf with ethyl ethoxymethylene malonate provided corresponding pyridylaminomethylenemalonates Va-Vd, respectively. Thermal cyclization of Va, Vc, and Vd yielded substituted ethyl 4-hydroxy-1,7-naphthyridine-3-carboxylates VIa, VIc, and VId. Compounds VIc and VId treated with morpholine gave 8-morpholino derivatives VIe and VIf. These compounds were ethylated to mixtures of N-ethylated (VIIa, VIIb) and O-ethylated products (VIIIa, VIIIb). Compound VIIIb was also prepared from ethyl 4-chloro-6-fluoro-8-morpholino-1,7-naphthyridine-3-carboxylate VIIIc and sodium ethanolate. Esters VIIa and VIIb were hydrolyzed under acidic conditions to the respective acids VIIc and VIId.