Robust and General Late-Stage Methylation of Aryl Chlorides: Application to Isotopic Labeling of Drug-like Scaffolds.
ACS Catal
; 13(17): 11541-11547, 2023 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-37671180
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
ACS Catal
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido