Department of Organic Chemistry, Institute of Chemistry , University of Campinas, UNICAMP , Campinas , São Paulo 13083-970 , Brazil.
Structural Genomics Consortium, Nuffield Department of Medicine , University of Oxford , Old Road Campus Research Building, Roosevelt Drive , Oxford OX3 7DQ , United Kingdom.
J Org Chem. 2019 Nov 1;84(21):14187-14201. doi: 10.1021/acs.joc.9b01844. Epub 2019 Sep 30.
A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted -imidazoles (23%-85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation-condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted -imidazoles (23%-69%, three steps). This approach was also employed in the synthesis of known inhibitor GSK3037619A.
基于酮的氧化反应，采用催化 HBr 和 DMSO，随后与醛的咪唑缩合，开发了一种一锅法和模块化方法来合成 2,4(5)-取代的咪唑。该方法提供了 29 种二取代咪唑（产率 23%-85%）。通过采用该氧化-缩合方案，实现了 20 种激酶抑制剂的三步合成，随后在咪唑环中进行溴化和铃木偶联，得到三取代咪唑（产率 23%-69%，三步）。该方法还用于合成已知抑制剂 GSK3037619A。
