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. The obtained carboxylates appeared to be convenient synthetic intermediates for the generation of the corresponding carboxamide libraries. Using these reagents, the parallel solution-phase synthesis of more than 500 substituted quinoline and 2-oxo-1,2-dihydroquinoline derivatives has been accomplished on the 50-100-mg scale. Simple manual techniques for parallel reactions using special CombiSyn synthesizers were coupled with easy purification procedures to give high-purity final products. The scope and limitations of the developed approaches are discussed.
Ivachtchenko
Alexandre V
AV
Chemical Diversity Labs, Inc., 11558 Sorrento Valley Rd., Suite 5, San Diego, California 92121, USA. av@chemdiv.com
Kobak
Vladimir V
VV
Ilyn
Alexey P
AP
Khvat
Alexander V
AV
Kysil
Volodymir M
VM
Williams
Caroline T
CT
Kuzovkova
Julia A
JA
Kravchenko
Dmitry V
DV
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
C507664:6-aminosulfonyl-2-oxo-1,2-dihydroquinoline-4-carboxamide; C507665:6-aminosulfonylquinoline-4-carboxamide; D011804:Quinolines; D013449:Sulfonamides