Synthesis of 5-substituted-1H-indol-2-yl-1H-quinolin-2-ones:: A novel class of KDR kinase inhibitors

被引：98

作者：

Kuethe, JT ^{[1
]}

Wong, A ^{[1
]}

Qu, CX ^{[1
]}

Smitrovich, J ^{[1
]}

Davies, IW ^{[1
]}

Hughes, DL ^{[1
]}

机构：

[1] Merck & Co Inc, Dept Proc Res, Rahway, NJ 07065 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2005年 / 70卷 / 07期

关键词：

D O I：

10.1021/jo0480545

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A number of approaches for the synthesis of the 1H-indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitor 1 are described. The preparation and reaction of trimethylsilylnitrobenzene 26 with 2-methoxy-3-quinolinecarboxaldehyde 28 afforded alcohol 30, which was the key intermediate for the preparation of the target compounds. Conversion of alcohol 30 to either nitroketone 36 or nitrostyrene 45 set the stage for reductive cyclization and the formation of indole 25. The quinolin-2-one functionality was unmasked in the last step to provide compound 1 in 56-60% overall yield from readily available starting materials.

引用

页码：2555 / 2567

页数：13

共 103 条

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