Synthesis and diuretic properties of n-aryl- 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1h-pyrrolo [3,2,1-ij]quinoline-5-carboxamides with electron-acceptor substituents in the anilide fragment

Abstract

In numerous studies of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides it has been convincingly shown that amidation of quinoline-3-carboxylic acids esters with alkyl-, aryl- and hetarylamines is the best way to obtain these compounds. As a rule, syntheses proceed smoothly and efficiently under rather mild conditions. However, in those cases when for formation of amides the temperature of 120-150°C and above is applied, partial destruction of the ester fragment may occur and, as a result, it pollutes the target products with specific impurities – the corresponding 4-hydroxy-1,2- dihydroquinolin-2-ones or their analogues. Application of 1H NMR spectroscopy allows to prove that the cause of ester fragments destruction, which sometimes can be observed when alkyl 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylates react with amines under harsh conditions, is water presented in the reagents or in the solvents. It becomes clear from this study that at the temperature of 95°C and higher the sensitivity of 4-hydroxy-2-oxo-1,2-dihydroquinoline- 3-carboxylic acids esters in a solution or a melt to hydrolysis increases significantly. Simple methods to minimize this undesirable process have been proposed – if the synthesis of N-substituted amides based on them requires such severe conditions, water should be removed from the reagents and solvents in order to avoid contamination of the final products with 4-hydroxy-1,2-dihydroquinolin-2-ones. The results of the diuretic properties study of new substituted anilides of 6-hydroxy-2-methyl-4-oxo-2,4-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid are discussed.