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A general method for the preparation of 2‐substituted‐4‐oxo‐3‐quinolinecarboxylic acids
Author(s) -
Kiely John S.,
Huang Suchin,
Lesheski Lawrence E.
Publication year - 1989
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570260630
Subject(s) - chemistry , substituent , carboxylic acid , hydrolysis , steric effects , reagent , iodide , medicinal chemistry , organic chemistry
Abstract A general method for preparing 2‐substituted‐4‐oxo‐3‐quinolinecarboxylic acids and 2‐substituted‐4‐oxo‐1,8‐naphthyridine‐3‐carboxylic acids as new analogs in the quinolone class of antiinfectives has been developed. The reaction of a Grignard reagent in the presence of copper(I) iodide with the 4‐oxo‐3‐quinolinecar‐boxylic acid esters and 4‐oxo‐1,8‐naphthyridine‐3‐carboxylic acid esters yields the desired 2‐substituent. Re‐introduction of the 2,3‐double bond is effected by phenylselenation of the 3‐position, oxidation to the selen‐oxide, and in situ syn‐elimisation. Depending on the degree of steric crowding between the 2‐substituent and the 3‐carboxylic acid group, hydrolysis of the ester to the carboxylic acid could be carried out under acidic or basic conditions.