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

Bagley, Mark, Baashen, Mohammed, Chuckowree, Irina, Dwyer, Jessica, Kipling, David Glyn and Davis, Terence ORCID: https://orcid.org/0000-0003-2780-0262 2015. Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner Syndrome Cells. Pharmaceuticals 8 (2) , pp. 257-276. 10.3390/ph8020257

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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
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	MDPI AG
ISSN:	1424-8247
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	1 June 2015
Last Modified:	04 May 2023 23:22
URI:	https://orca.cardiff.ac.uk/id/eprint/83159

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