Continuous flow processing as a tool for medicinal chemical synthesis

Continuous flow processing offers the potential to revolutionize the discovery, scale-up, and manufacturing of drug products. It offers safer handling and metering of hazardous materials, higher throughput, and greater reproducibility between batches. The use of multistep or telescoped flow helps streamline the synthesis process and avoids stockpiling of intermediates. Addition of workup modules for reaction quenching, liquid–liquid extraction, and solvent switching also assists in reducing the chance for error through manual intervention. The inclusion of inline monitoring through a variety of techniques has lead to the ability to self-optimize reactions. Further, continuous “make and screen” assays with appropriate computer control have resulted in optimization of physical properties such as binding affinities to biological targets. Herein we describe examples of some of the exciting and important developments in this field, culminating in machines capable of the “end-to-end” synthesis and formulation of API materials.