Completely N1-selective palladium-catalyzed arylation of unsymmetric imidazoles: application to the synthesis of nilotinib.
Completely N1-selective palladium-catalyzed arylation of unsymmetric imidazoles: application to the synthesis of nilotinib.
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DOI：
10.1021/ja2102373
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发表时间：
2012-01-11
影响因子：
15
通讯作者：
Buchwald, Stephen L.
中科院分区：
文献类型：
--
作者：
Ueda, Satoshi;Su, Mingjuan;Buchwald, Stephen L.
描述了不对称咪唑与芳基卤化物和三氟甲磺酸酯的完全 N1 选择性 Pd 催化芳基化。这项研究表明，咪唑对催化活性Pd(0)-配体配合物的原位形成具有很强的抑制作用。通过使用 Pd2(dba)3 和 L1 的预活化溶液，N-芳基化反应的效率得到了显着提高。从这些发现可以清楚地看出，虽然咪唑可以阻止 L1 与 Pd 的结合，但一旦配体与金属结合，这些杂环就不会取代它。本催化系统的实用性通过临床上重要的酪氨酸激酶抑制剂尼罗替尼的区域选择性合成得到证明。
The completely N1-selective Pd-catalyzed arylation of unsymmetric imidazoles with aryl halides and triflates is described. This study showed that imidazoles have a strong inhibitory effect on the in situ formation of catalytically-active Pd(0)-ligand complex. The efficacy of the N-arylation reaction was improved drastically by the use of pre-activated solution of Pd2(dba)3 and L1. From these findings it is clear that while imidazoles can prevent binding of L1 to the Pd, once the ligand is bound to the metal, these heterocycles do not displace it. The utility of the present catalytic system was demonstrated by the regioselective synthesis of clinically important tyrosine kinase inhibitor nilotinib.
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影响因子：
3.6
作者：
Collman, JP;Zhong, M;Costanzo, S
通讯作者：
Costanzo, S
影响因子：
5.4
作者：
Haneda, Satoshi;Ueba, Chigusa;Hayashi, Masahiko
通讯作者：
Hayashi, Masahiko
影响因子：
15
作者：
Fors, Brett P.;Buchwald, Stephen L.
通讯作者：
Buchwald, Stephen L.
影响因子：
15
作者：
Fors BP;Buchwald SL
通讯作者：
Buchwald SL
影响因子：
5.2
作者：
Collman, JP;Zhong, M
通讯作者：
Zhong, M