Robust and general late-stage methylation of aryl chlorides : application to isotopic labeling of drug-like scaffolds
Davenport, Elliot and Negru, Daniela E. and Badman, Geoff and Lindsay, David M. and Kerr, William J. (2023) Robust and general late-stage methylation of aryl chlorides : application to isotopic labeling of drug-like scaffolds. ACS Catalysis, 13 (17). pp. 11541-11547. ISSN 2155-5435 (https://doi.org/10.1021/acscatal.3c02761)
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Abstract
The preparation of isotopically labeled compounds for drug discovery and development presents a unique challenge. Both stable and radioactive isotopes must be incorporated into complex bioactive molecules as efficiently as possible, using precious, and often expensive, isotopically enriched reagents. Due to the ubiquity and importance of methyl groups in drug molecules, there is a requirement for a general, late-stage methylation that allows for the incorporation of both carbon and hydrogen isotopes. Herein, we report a highly efficient, robust palladium-catalyzed approach, optimized via high-throughput experimentation, for the methylation of aryl chlorides using potassium methyltrifluoroborate. A practically straightforward route to isotopically labeled methylating agents has also been developed, and the methodology applied to isotopologue synthesis, including the installation of isotopic labels in a range of drug-like scaffolds.
ORCID iDs
Davenport, Elliot, Negru, Daniela E., Badman, Geoff, Lindsay, David M. ORCID: https://orcid.org/0000-0003-4498-5094 and Kerr, William J. ORCID: https://orcid.org/0000-0002-1332-785X;-
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Item type: Article ID code: 86642 Dates: DateEvent1 September 2023Published16 August 2023Published Online4 August 2023AcceptedSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 31 Aug 2023 15:09 Last modified: 25 Sep 2024 02:10 URI: https://strathprints.strath.ac.uk/id/eprint/86642