Development of a Nitrene-Type Rearrangement for the Commercial Route of the JAK1 Inhibitor Abrocitinib
Christina G. Connor, Jacob C. DeForest, Phil Dietrich, Nga M., Kevin M. Doyle, Shane A. Eisenbeis, Elizabeth Greenberg, Sarah H. Griffin, Brian P. Jones, Kris Jones, Michael J. Karmilowicz, Rajesh Kumar, Chad A. Lewis, Emma L. McInturff, J. Christopher McWilliams, R. H. MEHTA, Bao D. Nguyen, Anil M. Rane, Brian Samas, Barbara Sitter, Howard W. Ward, Mark E. Webster
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.
Topics & Concepts
ReagentChemistryActive ingredientNitreneCombinatorial chemistryIngredientStereochemistryOrganic chemistryCatalysisPharmacologyFood scienceMedicineQuinazolinone synthesis and applicationsCytokine Signaling Pathways and InteractionsSynthesis and biological activity