New 7‐substituted quinolone antibacterial agents. <b>II</b>. The synthesis of 1‐ethyl‐1,4‐dihydro‐4‐oxo‐7‐(pyrazolyl, isoxazolyl, and pyrimidinyl)‐1,8‐naphthyridine and quinolone‐3‐carboxylic acids

Abstract

Abstract Synthetic methods for the construction of certain aromatic heterocyclic side chains for the quinolone anti‐bacterials have been provided. In particular a series of 7‐(pyrazol‐3 or 4‐yl, 4‐ or 5‐isoxazolyl and 4‐ or 5‐pyrimidinyl)‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐1,8‐naphthyridine and quinoline‐3‐carboxylic acids have been prepared. All of the heterocycles were prepared from masked 1,3‐dicarbonyl derivatives of nalidixic acid ( 9,17 ) or 7‐acetyl‐1‐ethyl‐1,4‐dihydro‐4‐oxo‐3‐quinoline carboxylic acids ( 8 ). These masked 1,3‐dicarbonyl derivatives were prepared by the use of t ‐butoxy‐bis‐dimethylaminomethane on the activated methyls of 9,19 and 8 . The pyrimidinyl analogs, substituted with a 2‐amino or a 2‐aminomethyl moiety, were the only derivatives with substantial antibacterial activity.