Stereocontrolled Synthesis of Delgocitinib, a JAK Inhibitor for the Treatment of Atopic Dermatitis

Abstract

Herein is reported the nine-step commercial synthesis of delgocitinib, a Janus kinase inhibitor approved for the treatment of atopic dermatitis in 2020. Its chiral spirodiamine core was selectively constructed by an intramolecular SN2 reaction of the suitably designed γ-lactone substrate and a few subsequent steps including a selective γ-lactone ring-opening reaction with potassium phthalimide, hydrazine-free mild dephthaloylation, and one-pot reduction of β- and γ-lactams. The route affords chemically and stereochemically pure delgocitinib in 39% yield.

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