Synthesis and Biological Activity of Novel N-1-Aryl-6-fluoro-5-methyl 1,8-Naphthyridine-3-carboxylic Acids

Quinolone Antibacterials

“…After 5-substitution with 4methoxybenzylamine, 5-( 4-methoxybenzylamino )-quinolones are obtained, and these can be deblocked in toluene with 36% hydrochloric acid Fig. 5-Methyl-(HAGEN andBOUZARD et al 1992a;JACQUET et al 1992;MATSUMOTO et al 1987MATSUMOTO et al /1988VEDA et al 1987), 5-ethyl-(HAGEN et al 1991BOUZARD et al 1992a), 5-phenyl-(BOUZARD et al 1992a), 5-methoxy-(DOMAGALA et al 1987), 5-dimethyl-amino-(DOMAGALA et al 1987), 5-fluoro-(PETERSEN et al 1987MORAN et al 1989), 5-chloro-(PETERSEN et al 1991b) and 5-bromo-quinolonecarboxylic acids (PETERSEN et al 1991b) or -naphthyridonecarboxylic acids are also prepared by the cycloaracylation method. Different routes for the synthesis of 5-amino-quinolones.…”

A Convenient One-Pot Synthesis of 1,8-Naphthyridones

“…Of the several ways of preparing this intermediate many are labor intensive. They require the formation of a 2-substituted pyridinyl acetate typically prepared via malonic ester acylation with 2-chloronicotinoyl chloride, followed by decarboxylation and then subsequent reaction with either dimethylamino dimethyl acetal, triethylorthoformate/acetic anhydride, or an iminochlorothioformate. − A second option is to employ the use of a thermal rearrangement/cyclization that requires temperatures as high as 350 °C. − In this paper, we disclose a new, one-pot method that involves the condensation of 2-chloronicotinoyl chloride with ethyl-3,3-dimethylaminoacrylate followed by in situ reaction with a variety of anilines to provide the desired 1,8-naphthyridone in a single flask.…”

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

“…The most common method for the synthesis of 1,8-naphthyridine-4-ones begins with condensation of ethyl 2-chloronicotinoylacetates I with either triethylorthoformate/acetic anhydride, dimethylamine dimethylacetal, or an iminochlorothioformate, followed by the reaction of intermediates II with amine to give the corresponding enamino ketoesters III. Subsequent intramolecular cyclization, under basic conditions, leads to 1,8-naphthyridone derivatives IV [25][26][27][28][29][30][31] (Chart 1). We have previously explored a new synthetic approach for the synthesis of polyfunctionally substituted 1,8-naphthyridin-2-one derivatives [32], and describe herein a new, efficient and convenient procedure for the synthesis of hitherto unreported polyfunctionally substituted 1,8-naphthyridin-2-one, 1,8-naphthyridin-2,7-dione.…”