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.

Trialkylammonium (most notably N,N,N-trimethylanilinium) salts are known to display dual reactivity through both the aryl group and the N-methyl groups. These salts have thus been widely applied in cross-coupling, aryl...

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The manufacturing route toward verinurad, an amphoteric, class II atropisomer that readily forms solvates, has proven to be highly complex. This previously required the isolation of intermediates with challenging physical properties and the application of cryogenic processes. New processes were designed and optimized, enabling the manufacture of 113 kg of verinurad in its desired polymorphic form. An interdisciplinary approach involving the synthesis, high-throughput experimentation, analytical chemistry, crystallization science, in silico modeling, and engineering was employed. Kinetic measurement of enantiomerically enriched verinurad salts confirmed that racemization occurred within the clearance time frame, thus mitigating safety concerns associated with inherent axial chirality in verinurad.