Flow Chemistry in Medicinal Chemistry: Applications to Bcr – Abl Kinase Inhibitors

• Paul Richardson^a

• ^aPfizer-La Jolla, Medicine Design, 10770 Science Center Drive, La Jolla, CA, 92121 USA

There continues to be an exponential growth in continuous/flow chemistry throughout the pharmaceutical industry with the advantages of this technology being well appreciated. While the ability to utilize such an approach to seamlessly scale a compound through development is often highlighted, the need to move rapidly in the discovery phase can be a barrier to investment in flow in medicinal chemistry laboratories. In addition, challenges exist most notably with heterogeneous reactions (insolubility of products) as well as with executing reactions prevalent in drug discovery most notably Pd-mediated cross-couplings. The current review highlights several case studies focusing on the application of flow chemistry technologies to the synthesis/discovery of inhibitors of Bcr-Abl kinase (such as imatinib, nilotinib, and ponatinib) and, through these, showcases a number of solutions/strategies to how these problems can be overcome.

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