Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells

Bagley, Mark C, Baashen, Mohammed, Chuckowree, Irina, Dwyer, Jessica E, Kipling, David and Davis, Terence (2015) Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells. Pharmaceuticals, 8 (2). pp. 257-276. ISSN 1424-8247

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Abstract

Microwave-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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry
Depositing User: Mark Bagley
Date Deposited: 18 Jan 2016 09:04
Last Modified: 19 Mar 2017 14:36
URI: http://sro.sussex.ac.uk/id/eprint/59251

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Project NameSussex Project NumberFunderFunder Ref
Alignment of Synthesis, Medicinal Chemistry and Structural Genomics to Accelerate (Strathclyde lead)G0926EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCILRKES 115428
2012 Doctoral Training Grant (EPSRC)G0942EPSRC-ENGINEERING & PHYSICAL SCIENCES RESEARCH COUNCILEP/K503198/1
UnsetUnsetBBSRCBB/D524140/1
A combined genetic and small molecule approach to studying the role of the p38/MK2 stress signallingG0931ESRC-ECONOMIC & SOCIAL RESEARCH COUNCILES/G037205/1
UnsetUnsetSaudi Cultural BureauI398