Development of a Nitrene-Type Rearrangement for the Commercial Route of the JAK1 Inhibitor Abrocitinib

Abstract

The development of a commercial route toward the JAK1 inhibitor abrocitinib is described. The application of a late-stage Lossen rearrangement provided the desired cis-diaminocyclobutane, which was subsequently sulfonylated using a novel water-tolerable triazole sulfonylating reagent to provide the active pharmaceutical ingredient.