The synthesis of a tritium, carbon-14, and stable isotope-labeled cathepsin C inhibitors
Paul Allen, Ryan A. Bragg, Moya Caffrey, Cecilia Ericsson, Michael J. Hickey, Lee P. Kingston and Charles S. Elmore
Version of Record online: 21 DEC 2016 | DOI: 10.1002/jlcr.3483
As part of a medicinal chemistry program aimed at developing a highly potent and selective cathepsin C inhibitor, tritium, carbon-14, and stable isotope-labeled materials were required. The synthesis of tritium-labeled methanesulfonate 5 was achieved via catalytic tritiolysis of a chloro precursor, albeit at a low radiochemical purity of 67%. Tritium-labeled AZD5248 was prepared via a 3-stage synthesis, utilizing amide-directed hydrogen isotope exchange. Carbon-14 and stable isotope-labeled AZD5248 were successfully prepared through modifications of the medicinal chemistry synthetic route, enabling the use of available labeled intermediates.