Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells

Pharmaceuticals

Mark C. Bagley¹  Mohammed Baashen¹  Irina Chuckowree¹  Jessica E. Dwyer¹  David Kipling²  Terence Davis² 

[1]Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex, BN1 9QJ, UK

[2] E-Mails:

[3]Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK

[4] E-Mails:

关键词: Suzuki-Miyaura;    cross-coupling;    MK2 inhibitor;    Werner syndrome;    cell aging;    pyrazoles;    heterocycles;    microwave-assisted synthesis;    boronic acid;   

DOI  :  10.3390/ph8020257

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.