pharmaceuticals-08-00257.pdf (1.09 MB)
Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells
journal contribution
posted on 2023-06-09, 00:02 authored by Mark BagleyMark Bagley, Mohammed Baashen, Irina Chuckowree, Jessica E Dwyer, David Kipling, Terence DavisMicrowave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells.
Funding
Alignment of Synthesis, Medicinal Chemistry and Structural Genomics to Accelerate (Strathclyde lead); G0926; EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCIL; RKES 115428
A combined genetic and small molecule approach to studying the role of the p38/MK2 stress signalling; G0931; ESRC-ECONOMIC & SOCIAL RESEARCH COUNCIL; ES/G037205/1
BBSRC; BB/D524140/1
2012 Doctoral Training Grant (EPSRC); G0942; EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCIL; EP/K503198/1
Saudi Cultural Bureau; I398
History
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- Published
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- Published version
Journal
PharmaceuticalsISSN
1424-8247Publisher
MDPIExternal DOI
Issue
2Volume
8Page range
257-276Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-01-18First Open Access (FOA) Date
2016-01-18First Compliant Deposit (FCD) Date
2016-01-15Usage metrics
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