Rapid Access to Kinase Inhibitor Pharmacophores by Regioselective C-H Arylation of Thieno[2,3-d]pyrimidine
Rapid Access to Kinase Inhibitor Pharmacophores by Regioselective C-H Arylation of Thieno[2,3-d]pyrimidine
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DOI：
10.1021/acs.orglett.0c00143
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发表时间：
2020-02-21
期刊：
影响因子：
5.2
通讯作者：
Itami, Kenichiro
中科院分区：
文献类型：
--
作者：
Yamada, Shuya;Flesch, Kaylin Nicole;Itami, Kenichiro
噻吩并[2，3-d]-嘧啶的区域选择性C-H芳基化反应在钯催化下完成。噻吩并-[2，3-d]嘧啶在C6-位与芳基碘反应，在C5-位与芳基硼酸反应，显示出优异的区域选择性。机理研究表明，区域选择性由钯催化剂的性质控制：阳离子钯有利地芳基化C5-位置。这种直接芳基化的效用已在激酶抑制剂及其衍生物的流线型合成中得到强调。
Regioselective C-H arylations of thieno[2,3-d]-pyrimidine are accomplished under palladium catalysis. Thieno-[2,3-d]pyrimidines react with aryl iodides at the C6-position and with aryl boronic acids at the C5-position, showing excellent regioselectivity. Mechanistic investigations indicate that the regioselectivity is controlled by the nature of the palladium catalyst: the cationic palladium favorably arylates the C5-position. The utility of this direct arylation has been highlighted in the streamlined synthesis of kinase inhibitors and their derivatives.