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Microwave-assisted Ullmann C-S bond formation: synthesis of the P38alpha MAPK clinical candidate VX-745
journal contribution
posted on 2023-06-08, 12:30 authored by Mark BagleyMark Bagley, Terence Davis, Matthew C Dix, Vincenzo Fusillo, Morgane Pigeaux, Michal J Rokicki, David KiplingMicrowave irradiation promotes the rapid and efficient reaction of a thiophenol and aryl or heteroaryl halide using a copper or palladium catalyst and a range of ligands, depending upon substrate. Of particular utility is the use of copper(I) iodide (5 mol %) and trans-cyclohexane-1,2-diol as ligand under basic conditions and microwave irradiation to give the corresponding sulfide in high yield. This method for C-S bond formation is applied in the four-step synthesis of the clinical candidate VX-745 in 38% overall yield. The inhibitory activity of VX-745 against p38alpha MAPK is confirmed in Werner syndrome dermal fibroblasts at 1.0 microM concentration by immunoblot assay.
History
Publication status
- Published
Journal
Journal of Organic ChemistryISSN
1520-6904Publisher
American Chemical SocietyExternal DOI
Issue
21Volume
74Page range
8336-42Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-10-29Usage metrics
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