Verubecestat is an inhibitor of β-secretase being evaluated for the treatment of 
Alzheimer's disease. The first-generation route relies on an amide coupling with 
a functionalized aniline, the preparation of which introduces synthetic 
inefficiencies. The second-generation route replaces this with a 
copper-catalyzed C-N coupling, allowing for more direct access to the target. 
Other features of the new route include a diastereoselective Mannich-type 
addition into an Ellman sulfinyl ketimine and a late-stage guanidinylation.