Chapter 6: Palladium- and Copper-catalysed C–N Cross-coupling in Drug Discovery

The impact of palladium- and copper-catalysed C–N cross-coupling reactions in the pharmaceutical industry is immense. These methodologies are routinely applied to the expedient synthesis of complex (hetero)arylamines utilizing a breadth of amine feedstocks including basic alkylamines and weakly nucleophilic N–H azoles. The focus of this chapter is to illustrate the power and complementarity of palladium and copper C–N cross-coupling reactions. To this end, we will discuss recent literature examples showcasing both the development of structure–activity relationship studies in early drug discovery and the optimization of late-stage process development of clinical candidates. In addition, recent advances of challenging C–N cross-coupling reactions will be highlighted within the context of future applications to support drug discovery and development.