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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