title: Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells.
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.
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex, BN1 9QJ, UK. m.c.bagley@sussex.ac.uk.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Bagley
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex, BN1 9QJ, UK. baashen2000@hotmail.com.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Baashen
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex, BN1 9QJ, UK. I.Chuckowree@sussex.ac.uk.
authors.forename: Irina
authors.initials: I
authors.lastname: Chuckowree
authors.affiliation: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, East Sussex, BN1 9QJ, UK. J.E.Dwyer@sussex.ac.uk.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Dwyer
authors.affiliation: Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK. KiplingD@cardiff.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Kipling
authors.affiliation: Institute of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK. davist2@cardiff.ac.uk.
authors.forename: Terence
authors.initials: T
authors.lastname: Davis
keywords: MK2 inhibitor; Suzuki-Miyaura; Werner syndrome; boronic acid; cell aging; cross-coupling; heterocycles; microwave-assisted synthesis; pyrazoles