Journal of Combinatorial Chemistry 2007-01-01

Efficient solid-phase synthesis of 2-substituted-3-hydroxy-4(1H)-quinolinone-7-carboxamides with two diversity positions.

Miroslav Soural, Viktor Krchnák

文献索引：J. Comb. Chem. 9(5) , 793-6, (2007)

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摘要

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.