Our neuroscience group investigated a series of 1,4,5-trisubstituted-1,2,3-triazole derivatives that lead to the discovery of a potent P2X7 antagonist for the potential treatment of depressive disorders. The progress made by our Discovery Sciences Chemistry Team toward the development of an efficient chiral route to 1,4,5-trisubstituted-1,2,3-triazole 1 is described in this poster. The key feature of this route is a regioselective one-pot three-component copper(I)-catalyzed azide-alkyne cycloaddition/allylation reaction to assemble our 1,4,5-allyl-trisubstituted-1,2,3-triazole intermediate. Further functionalization of the allyl substituent followed by cyclization provided our final compound 1. Using this new synthesis route provided a chiral pathway to our fused bicyclic triazole ring that had been difficult to prepare by previous routes and is amenable to large-scale preparation.

Chiral synthesis to a 1,4,5-trisubstituted-1,2,3-triazole involving a one-pot regioselective copper(I)-catalyzed [3+2]-azide-alkyne cycloaddition/allylation reaction

252nd National Meeting (2016)

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