The pyrrolidine moiety is a common structural motif found in many FDA-approved drugs.  We recently disclosed a series of RORγt inverse agonists in which the pyrrolidine moiety is embedded in the tricylic core. Initially, this pyrrolidine was synthesized in a racemic sense and in low yield following a four-step sequence. In this presentation, we will discuss the discovery of novel ambiphilic reagents for use in annulation reactions, which generate the desired pyrrolidine in a single step with high diastereoselectivity and in high yield. These annulation reactions were also found to have a broad scope and enabled both a medicinal chemistry structure activity relationship (SAR) campaign and the large scale synthesis of the program tricyclic core.

Discovery of ambiphilic reagents for the synthesis of chiral pyrrolidines

2019 Fall National Meeting

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