Preparation of 3-arylmethylindoles as selective COX-2 inhibitors

被引：32

作者：

Campbell, JA ^{[1
]}

Bordunov, V ^{[1
]}

Broka, CA ^{[1
]}

Dankwardt, J ^{[1
]}

Hendricks, RT ^{[1
]}

Kress, JM ^{[1
]}

Walker, KAM ^{[1
]}

Wang, JH ^{[1
]}

机构：

[1] Roche Palo Alto, Dept Med Chem, Palo Alto, CA 94304 USA

来源：

TETRAHEDRON LETTERS | 2004年 / 45卷 / 19期

关键词：

reductive indole alkylation; 3-arylmethylindole; 3-benzylindole; COX-2; inhibitors; TMSOTf; palladium;

D O I：

10.1016/j.tetlet.2004.03.068

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The 3-arylmethylation of indoles using TMSOTf/Et3SiH with a wide variety of substituted benzaldehydes has been accomplished. Under these mild Lewis acid mediated reductive conditions, it was demonstrated that indoles bearing both 6-MeSO2, and 2-methyl substituents could be 3-arylmethylated in good to excellent yields to afford the corresponding 3-arylmethyl indoles, effective as selective COX-2 inhibitors. I it addition, the viability of this method for the reductive alkylation of indoles by ketones was demonstrated and shown to be C-3 regioselective. For indoles bearing both a 6-MeSO2, and 2-cyano substituent where this indole reductive alkylation methodology was unsuccessful, all unprecedented Pd(0) mediated arylorganozinc Coupling With the requisite Substituted 3-methylcarbonatomethylindole proved Successful in affording the desired 2-cyano-6-MeSO2-3-arylmethylindoles effective as selective COX-2 inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3793 / 3796

页数：4

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