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

被引：8

作者：

Bagley, Mark C. ^{[1
]}

Baashen, Mohammed ^{[1
]}

Chuckowree, Irina ^{[1
]}

Dwyer, Jessica E. ^{[1
]}

Kipling, David ^{[2
]}

Davis, Terence ^{[2
]}

机构：

[1] Univ Sussex, Dept Chem, Sch Life Sci, Brighton BN1 9QJ, E Sussex, England

[2] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff CF14 4XN, S Glam, Wales

来源：

PHARMACEUTICALS | 2015年 / 8卷 / 02期

基金：

英国工程与自然科学研究理事会; 英国经济与社会研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

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

D O I：

10.3390/ph8020257

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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.

引用

页码：257 / 276

页数：20

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