Department of Chemistry, Indian Institute of Technology Madras, Chennai-, 600036, India.
Angew Chem Int Ed Engl. 2017 Dec 18;56(51):16197-16201. doi: 10.1002/anie.201708138. Epub 2017 Nov 27.
A novel and efficient one-pot method has been developed for the synthesis of cyclopropane-fused bicyclic amidines on the basis of a CuBr -mediated oxidative cyclization of carbanions. The usefulness of this unique multicomponent strategy has been demonstrated by the use of a wide variety of substrates to furnish novel cyclopropane-containing amidines with a quaternary center in very good yields. This ketenimine-based approach provides straightforward access to biologically active and pharmaceutically important 3-azabicyclo[n.1.0]alkane frameworks under mild conditions. The synthetic power of this methodology is exemplified in the concise synthesis of the pharmaceutically important antidepressant drug candidate GSK1360707 and key intermediates for the synthesis of amitifadine, bicifadine, and narlaprevir.
一种新颖且高效的一锅法已经基于 CuBr 介导的碳负离子氧化环化反应，被开发用于合成环丙烷并环双胍。这种独特的多组分策略的实用性已经通过使用各种底物得到了证明，以非常好的收率得到了新型含有季碳原子的环丙烷双胍。这种基于偕亚胺的方法在温和条件下提供了直接获得生物活性和药物重要性的 3-氮杂双环[n.1.0]烷骨架的途径。这种方法学的合成能力在简洁合成药物重要的抗抑郁候选药物 GSK1360707 和 amitifadine、bicifadine 和 narlaprevir 的合成的关键中间体中得到了例证。
