Palladium-Catalyzed Regioselective Arylation of Imidazo[1,2-b][1,2,4]triazine: Synthesis of an α2/ 3-Selective GABA Agonist
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 GABAA α2/ 3-selective agonist, is described. The seven-step, chromatography-free synthesis was demonstrated on a multi-kilo...
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Veröffentlicht in: | Journal of organic chemistry 2005-07, Vol.70 (15), p.5938-5945 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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 GABAA α2/ 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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ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/jo0507035 |