Green One‐Pot Chemo‐Enzymatic Synthesis of a Key Chiral Amine Intermediate: Useful to Pralsetinib Synthesis

Abstract A facile, chemo‐enzymatic one‐pot and scalable procedure was developed for the synthesis of the key chiral intermediate of pralsetinib in an aqueous micellar medium. This method afforded the desired chiral intermediate with high enantioselectivity without the use of any expensive chiral ligands and toxic reagents that are difficult to handle. A green synthesis of chiral intermediate of pralsetinib was carried out using an enzyme ATA‐260 in an aqueous media with >99.9 % ee that was confirmed by a chiral reverse‐ phase HPLC. This study hence represents a mild and scalable procedure for the synthesis of the chiral intermediate of Pralsetinib with yields exceeding 80 %, which forms a crucial step in the synthesis of the anti‐ cancer drug.