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

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posted on 2023-06-09, 00:02 authored by Mark BagleyMark Bagley, Mohammed Baashen, Irina Chuckowree, Jessica E Dwyer, David Kipling, Terence Davis
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.

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

Publication status

  • Published

File Version

  • Published version

Journal

Pharmaceuticals

ISSN

1424-8247

Publisher

MDPI

Issue

2

Volume

8

Page range

257-276

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-18

First Open Access (FOA) Date

2016-01-18

First Compliant Deposit (FCD) Date

2016-01-15

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