Palladium-Catalyzed Regioselective Arylation of Imidazo[1,2-b][1,2,4]triazine: Synthesis of an α2/3-Selective GABA Agonist
The Journal of Organic Chemistry2005Vol. 70(15), pp. 5938–5945
Citations Over TimeTop 10% of 2005 papers
Donald R. Gauthier, John Limanto, Paul N. Devine, Richard Desmond, Ronald H. Szumigala, Bruce S. Foster, R. P. Volante
Abstract
A convergent, practical, and efficient synthesis of 2',6-difluoro-5'-[3-(1-hydroxy-1-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.
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