1416178-01-2Relevant academic research and scientific papers
Lab-scale preparation of a novel carbocyclic chemokine receptor antagonist
Teleha, Christopher A.,Branum, Shawn,Zhang, Yongzheng,Reuman, Michael E.,Van Der Steen, Luc,Verbeek, Marc,Fawzy, Nagy,Leo, Gregory C.,Kang, Fu-An,Cai, Chaozhong,Kolpak, Michael,Beauchamp, Derek A.,Wall, Mark J.,Russell, Ronald K.,Sui, Zhihua,Vanbaelen, Hilde
, p. 1622 - 1629 (2014)
The preparation of a novel chemokine receptor type 2 (CCR-2) antagonist is described on a 135 g scale. The synthesis of an all-carbon bicyclic core was accomplished using a radical cyclization strategy using chiral precursors, wherein elaboration led to N-Boc carboxylic acid in good yield. After amidation using a traditional coupling reaction, a reductive amination using enantiomerically enriched 3-methoxy-4-pyranone led to the final compound. Although several steps of the syntheses involved reagents that would not be preferred in process and chromatography was used to provide the free-base diastereomer of the final succinate salt, the overall route went through stable intermediates that could be used for future scale-up. This lab-scale synthesis struck a balance between a quick scale-up and a more thorough process review of all possible methods and routes.
