Electrochemical bromination of late stage intermediates and drug molecules

Abstract Aromatic C H bromination is one of the applications of late stage functionalization that provides precursors for generation of radio-labelled compounds to support drug metabolism and pharmacokinetic (DMPK) studies or provide a “handle” for further functionalization to expand SAR studies without having to resort to de novo synthesis. Electrochemical aromatic bromination was attempted on late stage intermediates and drug molecules such as cytidine, uridine, Tenofovir, MK-4618, Sch48973 and MK-8457. The reactions were conducted under mild galvanostatic electrolysis condition in aqueous NaBr solution. The brominated products were obtained and converted to the corresponding tritium labelled products. Electrochemical methodology provides an alternative way to quickly generate aryl bromides of late stage intermediates or drug molecules that are very useful in drug discovery.