Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.
Current affiliation: Novartis Pharma AG, CH-4002 Basel, Switzerland.
Molecules. 2019 Jul 3;24(13):2447. doi: 10.3390/molecules24132447.
A novel flow-based approach for the preparation of benzimidazol-2-one () scaffold by the 1,1'-carbonyldiimidazole (CDI)-promoted cyclocarbonylation of -phenylenediamine () is reported. Starting from a preliminary batch screening, the model reaction was successfully translated under flow conditions and optimised by means of design of experiment (DoE). The method allowed the efficient preparation of this privileged scaffold and to set up a general protocol for the multigram-scale preparation in high yield, purity, and productivity, and was successfully applied for the multigram flow synthesis of -(2-chlorobenzyl)-5-cyano-benzimidazol-2-one, which is a key synthon for hit-to-lead explorations in our anti-inflammatory drug discovery program.
本文报道了一种新颖的基于流动的方法，通过 1,1'-羰基二咪唑（CDI）促进 -苯二胺（）的环羰化反应，制备苯并咪唑-2-酮（）支架。从初步的分批筛选开始，成功地在流动条件下转化了模型反应，并通过实验设计（DoE）进行了优化。该方法允许有效地制备这种特权支架，并建立了用于多克规模制备的通用协议，具有高产率、高纯度和高生产效率，并且成功地应用于 -(2-氯苄基）-5-氰基-苯并咪唑-2-酮的多克流动合成，这是我们抗炎药物发现计划中从命中到先导探索的关键合成子。
