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Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

preprint
submitted on 08.01.2020 and posted on 09.01.2020 by Sean Reilly, Frank Bennett, Patrick Fier, Sumei Ren, Neil A. Strotman
A late-stage 18O labeling approach of sulfonamides that employs the corresponding unlabeled molecule as the starting material was developed. Upon deamination of the sulfonamide, a sulfinate intermediate was isotopically enriched using eco-friendly reagents H218O and 15NH3(aq) to afford a M+5 isotopologue of the parent compound. This degradation-reconstruction approach afforded isolated yields of up to 96% for the stable isotope labeled (SIL) sulfonamides, and was compatible with multiple marketed therapeutics, including celecoxib, on a gram scale. The SIL products also exhibited no 18O/16O back exchange under extreme conditions, further validating the utility of this green strategy for drug labeling for both in vitro and in vivo use. This procedure was also adapted to include pharmaceutically relevant methyl sulfones by using 13CH3, affording M+5 isotopic enrichment, thereby illustrating the broad utility of this methodology.

History

Email Address of Submitting Author

sean.reilly@merck.com

Institution

Merck & Co., Inc

Country

United States of America

ORCID For Submitting Author

0000-0002-1656-1895

Declaration of Conflict of Interest

No conflict of interest

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