Development and Proof of Concept for a Large-Scale Photoredox Additive-Free Minisci Reaction

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 proofof-concept data for the future application of this technology in the clinical manufacture of ceralasertib.

Automated summary

New route development activities for ceralasertib have led to the discovery of an efficient, acid additive-free, photoredox Minisci reaction. Mechanistic understanding and optimization of the catalyst system has significantly enhanced the reaction rate, with a large-scale continuous photoflow process providing promising proof-of-concept data for future clinical manufacture applications of ceralasertib.