Efficient solid-phase synthesis of 2-substituted-3-hydroxy-4(1H)-quinolinone-7-carboxamides with two diversity positions.
A highly efficient solid-phase synthesis of 2-substituted-3-hydroxy-4(1H)-quinolinone-7-carboxamides was developed using anthranilates and bromoketones as the key synthons. Primary amines immobilized to an acid-cleavable BAL linker were acylated with 1-methyl-2-aminoterephtalate. After cleavage of the methyl ester, bromoketones were used to form resin-bound phenacyl esters. Acid-mediated cleavage and subsequent cyclization in solution afforded 3-hydroxy-4(1H)-quinolinones in high purity and yield. Highly efficient solid-phase synthesis (purity>90%, yield>80%, synthetic time=2 days using commercially available synthons) is amenable to high-throughput/combinatorial synthesis to match the high-throughput screening capability.
Department of Chemistry and Biochemistry, 251 Nieuwland Science Center, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Miroslav
M
Soural
Viktor
V
Krchnák
D000577:Amides / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry
D000577:Amides; D015363:Quinolones