A scalable synthesis of a pan-JAK inhibitor is described. The original synthesis by the Medicinal Chemistry group has been modified to develop a new protecting group strategy, a 3-step telescoped synthesis to generate an imidazole ring from a nitrile, and a telescoped borylation/Suzuki coupling sequence as well as to replace HATU with process-friendly CDI in the final amidation step. Efficient API purification and polymorph interconversion protocols have been implemented to obtain API with the desired purity and physical properties for an inhaled formulation.
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