Palladium-catalyzed regioselective arylation of imidazo[1,2-b][1,2,4]triazine:: Synthesis of an α2/3-selective GABA agonist

被引：53

作者：

Gauthier, DR ^{[1
]}

Limanto, J ^{[1
]}

Devine, PN ^{[1
]}

Desmond, RA ^{[1
]}

Szumigala, RH ^{[1
]}

Foster, BS ^{[1
]}

Volante, RP ^{[1
]}

机构：

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

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2005年 / 70卷 / 15期

关键词：

D O I：

10.1021/jo0507035

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A convergent, practical, and efficient synthesis of 2',6-difluoro-5'-[3-(l-hydroxy-l-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile (1), an orally active GABA(A) alpha(2/3)-selective agonist, is described. The seven-step, chromatography-free synthesis was demonstrated on a multi-kilogram scale and utilized biaryl bromide 6 and imidazotriazine 22 as key intermediates. Biaryl bromide 6 was prepared via a highly selective aromatic bromination. The regioselective condensation of aminotriazine 15 with chloroacetaldehyde provided the desired imidazotriazine intermediate 22. A highly regioselective palladium-catalyzed arylation in the final step highlights the efficiency of the route.

引用

页码：5938 / 5945

页数：8

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