Regiospecific synthesis of 1,5-disubstituted-1H-pyrazoles containing differentiated 3,4-dicarboxylic acid esters via Suzuki coupling of the corresponding 5-trifluoromethane sulfonates

被引：21

作者：

Dragovich, Peter S. ^{[1
]}

Bertolini, Thomas M. ^{[1
]}

Ayida, Benjamin K. ^{[1
]}

Li, Lian-Sheng ^{[1
]}

Murphy, Douglas E. ^{[1
]}

Ruebsam, Frank ^{[1
]}

Sun, Zhongxiang ^{[1
]}

Zhou, Yuefen ^{[1
]}

机构：

[1] Anadys Pharmaceut Inc, San Diego, CA 92121 USA

来源：

TETRAHEDRON | 2007年 / 63卷 / 05期

关键词：

D O I：

10.1016/j.tet.2006.11.053

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A general procedure is described for the regiospecific preparation of 1-substituted-5-hydroxy-1H-pyrazoles containing differentiated ester moieties at the 3- and 4-positions. This process involves the coupling of monosubstituted benzyl carbazates with various malonyl chlorides or acids, deprotection of the coupling products via catalytic hydrogenation, and subsequent derivatization of the resulting hydrazides with monoalkyl oxalyl chlorides. The 5-hydroxy-1H-pyrazoles are readily transformed to the corresponding trifluoromethane sulfonates, which undergo palladium-mediated Suzuki coupling with a variety of boronic acids (aryl, heteroaryl, and alkenyl) in moderate to excellent yields (24-92%). The ester groups present in one of the resulting 1,5-disubstituted-1H-pyrazoles are further modified by selective hydrolysis or conversion to the corresponding dicarboxylic acid derivative followed by selective mono-esterification. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1154 / 1166

页数：13

共 24 条

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