Lab-Scale Preparation of a Novel Carbocyclic Chemokine Receptor Antagonist

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 ami...

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Bibliographic Details
Published in:Organic process research & development 2014-12, Vol.18 (12), p.1622-1629
Main Authors: 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
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op500265z