Development and Proof of Concept for a Large-Scale Photoredox Additive-Free Minisci Reaction
M. A. Graham, Gary M. Noonan, Janette Cherryman, James J. Douglas, Miguel Gonzalez, Lucinda V. Jackson, Kevin Leslie, Zhiqing Liu, David McKinney, Rachel H. Munday, Chris D. Parsons, David Whittaker, En-xuan Zhang, Jun-wang Zhang
Abstract
New route development activities toward ceralasertib (AZD6738) have resulted in the discovery of an efficient, acid additive-free, photoredox Minisci reaction. Mechanistic understanding resulting from LED-NMR reaction profiling, quantum yield measurements, and Stern–Volmer quenching studies have enabled optimization of the catalyst system, resulting in a significant enhancement in the rate of reaction. A large-scale continuous photoflow process has been developed, providing encouraging proof-of-concept data for the future application of this technology in the clinical manufacture of ceralasertib.