A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931).

David A Thaisrivongs William J MorrisLushi TanZhiguo J SongThomas W LyonsJacob H WaldmanJohn R NaberWenyong ChenLu ChenBaoyun ZhangJun Yang

Published in: Organic letters (2018)

The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guanidinylation procedure to form the key iminothiadiazine dioxide core.

Keyphrases

electron transfer
minimally invasive