Enabling Synthesis of ABBV-2222, A CFTR Corrector for the Treatment of Cystic Fibrosis

An enabling preclinical synthetic route to cystic fibrosis candidate ABBV-2222 is described. Two stereoselective steps provide access to an aminochroman intermediate with excellent control, and a late-stage demethylation/difluoromethylation sequence provides efficient access to the target molecule.