Enamine Ltd. , Chervonotkatska Street 78 , Kyiv 02094 , Ukraine.
Institute of Organic Chemistry , National Academy of Sciences of Ukraine , Murmanska Street 5 , Kyiv 02660 , Ukraine.
J Org Chem. 2019 Dec 6;84(23):15212-15225. doi: 10.1021/acs.joc.9b02258. Epub 2019 Nov 8.
A facile synthetic route toward either 3- or 5-fluoroalkyl-substituted isoxazoles or pyrazoles containing an additional functionalization site was developed and applied on a multigram scale. The elaborated approach extends the scope of fluoroalkyl substituents for introduction into the heterocyclic moiety, and uses convenient transformations of the side chain for incorporation of fluoroalkyl-substituted azoles into the structures of biologically active molecules. The utility of the obtained building blocks for isosteric replacement of alkyl-substituted isoxazole and pyrazole was shown by the synthesis of fluorinated Isocarboxazid and Mepiprazole analogues.
开发了一种简便的合成路线，可以将 3-或 5-氟烷基取代的异恶唑或吡唑（其中含有额外的官能团化位点）进行合成，并且可以在多克规模上进行应用。该方法扩展了将氟烷基取代基引入杂环部分的范围，并利用侧链的方便转化，将氟烷基取代的唑类化合物引入到生物活性分子的结构中。所获得的砌块可用于烷基取代的异恶唑和吡唑的等排取代，通过合成氟代异卡波肼和甲哌吡唑类似物证明了其用途。
