Exploiting Nickel Cross-coupling Catalysis for the Practical Synthesis and Functionalization of Pharmaceutically Relevant Organic Molecules

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In the fast-paced drug discovery and development process, synthetic chemists require efficient methods of preparing complex organic molecules that contain carbon, hydrogen, and a diversity of 'heteroatoms' (e.g., nitrogen, oxygen, sulfur, fluorine and other elements) under mild, 'user-friendly' conditions. One method involves the use of metal catalysts that allow smaller portions of targeted organic molecules to be 'clipped together' in a process called cross-coupling, thus allowing for the assembly of potential active pharmaceutical ingredients (APIs) in a more streamlined and cost-effective manner. This collaborative research project will seek to exploit recent expertise in sustainable cross-coupling catalysis developed by the applicant's research group, in addressing specific unmet synthetic chemistry challenges faced by the industrial partner (Paraza Pharma Inc., Montreal, QC) with regard to the targeted synthesis and/or modification of heteroatom-dense compounds within proprietary APIs. In particular, the industrial partner requires the development of methodologies that make use of cheap and abundant reaction partners (e.g., heteroaryl chlorides), as well as Earth abundant catalysts (rather than precious metal catalysts that are commonly employed). Once developed, these synthetic protocols can be exploited directly by scientists at Paraza Pharma Inc. in proprietary API synthesis and functionalization. Success in this project will greatly accelerate the industrial partner's drug development program, thereby leading to more rapid identification of novel therapies to the benefit of all Canadians.