Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells.
Microwave-Assisted Synthesis of a MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome Cells.
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DOI：
10.3390/ph8020257
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发表时间：
2015-06-03
期刊：
影响因子：
--
通讯作者：
Davis T
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文献类型：
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作者：
Bagley MC;Baashen M;Chuckowree I;Dwyer JE;Kipling D;Davis T
微波辅助Suzuki-Miyaura交叉偶联反应已被用于合成三种不同的MAPKAPK 2（MK 2）抑制剂，以研究Werner综合征（WS）细胞的加速老化，包括2-氯喹啉与3-吡啶基硼酸的交叉偶联、芳基溴与吲哚基硼酸的偶联以及3-氨基-4-溴吡唑与4-氨基甲酰基苯基硼酸的反应。在所有这些方法中，Suzuki-Miyaura反应在微波辐射下使用钯催化剂快速且相对有效。该方法被纳入一个快速的3-步微波辅助法合成MK2抑制剂，包括3-氨基吡唑形成，吡唑C-4溴化使用N-溴代琥珀酰亚胺（NBS），和Suzuki-Miyaura交叉偶联的吡唑溴与4-氨基甲酰基苯基硼酸，得到目标4-芳基吡唑在35%的总产率，适合于在WS细胞中的研究。
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.