Parallel liquid-phase synthesis of N-substituted 6-aminosulfonyl-2-oxo-1,2-dihydroquinoline-4-carboxamide and 6-aminosulfonylquinoline-4-carboxamide derivatives.

Two efficient strategies for solution-phase parallel synthesis of libraries of quinoline derivatives are described. The first synthetic pathway features the Pfitzinger reaction of isatin with diethyl malonate and sulfochlorination of the resulting 2-oxo-1,2-dihydroquinoline-4-carboxylate followed by generation of sulfonamide library. The second strategy employs the unusual behavior of 5-sulfamoylisatins in Pfitzinger reactions, which results in formation of 6-sulfamoyl-4-carboxyquinolines instead of the anticipated 2-oxo-1,2-dihydroquinoline structures.