Improved Synthesis of 5-Ethylsulfonyl-2-methoxyaniline

5-Ethylsulfonyl-2-methoxyaniline is an extremely versatile molecule used in the preparation of a number of different compounds with biological activities targeting kinases, including several VEGFR2 inhibitors 1 – 3 and a CLK inhibitor. 1 Closely related sulfone analogues of 5-ethylsulfonyl-2-methoxyaniline have also been used in the preparation of antimalarials, 4 muscarinic M1 agonists, 5 topoisomerase inhibitors 6 and utrophin upregu-lators. 7 A compound synthesized from 5-ethylsulfonyl-2-methoxyaniline is featured in the Protein Database (PDB ID: 1y6a). 3 Our lab in the preparation of this compound when we were designing inhibitors of serine/threonine-protein kinase 16 (STK16). Since the compound is not commercially available, we first tried to reproduce a recently reported procedure 8 detailed in Scheme 1.