Version 2 2024-01-18, 18:06Version 2 2024-01-18, 18:06
Version 1 2024-01-17, 19:08Version 1 2024-01-17, 19:08
journal contribution
posted on 2024-01-18, 18:06authored byDiane N. Le, Mikhail Reibarkh, Daniel A. DiRocco, Yining Ji
The development of a nucleophilic aromatic substitution
(SNAr) reaction for the synthesis of belzutifan and related
analogues
is disclosed. This classical transformation suffered from reaction
stalling, despite prolonged reaction times. Through experimental and
mechanistic studies, product inhibition was revealed and rationalized.
Herein, we describe our efforts to overcome this synthetic challenge
and demonstrate the importance of the judicious choice of the solvent
to achieve reactivity.