As part of a general investigation of new antibacterial agents,1 we have prepared a series of 1-alkyl-1,8-naphthyridin-4-one-3-carboxylic acid derivatives. Several members of the series, listed in Table I, were found to be highly effective antibacterial agents both in vitro and in vivo.These 1-alkyl-1,8-naphthyridines are prepared as outlined. The appropriate 6-substituted-2-aminopyridine (I) is condensed with diethyl ethoxymethylenemalonate and the resulting diethyl N-(6substituted-2-pyridyl)-aminomethylenemalonate (II) is cyclized in refluxing Dowtherm A or diethyl phthalate to give the ethyl 4-hydroxy-1,8-naphthyridine-3-carboxylate derivative (III).2 Hydrolysis of the ester (III) to the corresponding acid and alkylation in alcoholwater with potassium hydroxide gives the desired 1-alkyl-1,8-naphthyridin-4-one-3-carboxylic acid (IV). Alternatively, the same
Vol. 66 and recrystallized from 50% acetic acid. The product, 3.2 g. (20%) melted at 165.6-167°. Prepared by another procedure1• this product has been reported as melting at 167°.
25% sodium hydroxide solution. Ten grams of nicotine base was dissolved in the hypochlorite solution followed by 0.25 g. of nickel sulfate in a little water. The mixture was heated to 50°and held at 50-55°until the available chlorine was practically exhausted (about three hours). The catalyst was filtered off, the solution was acidulated With sulfuric acid and heated to boiling to expel the carbon dioxide, then neutralized. An excess of copper sulfate solution was added and the copper nicotinate was filtered off. The nicotinic acid was isolated from the copper salt by the usual methods; yield, 4.54 g. (60%). After one recrystallization from water, about 90% pure acid was obtained; m. p. 235-236°.
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