Process Research and Scale-up of the κ-Opioid Receptor Agonist CJ-15,161 Drug Candidate


  • Brian M. Andresen
  • Brian C. Vanderplas
  • John L. Tucker
  • Janice E. Sieser
  • Maxime Riou
  • Teresa M. Makowski
  • Joel M. Hawkins
  • Melina Girardin
  • Arun Ghosh
  • Kristina Dupont-Gaudet
  • Nga M. Do
  • Keith M. DeVries
  • Michel Couturier
  • Stéphane Caron
  • Timothy J.N. Watson



N-arylation, Aziridinium, Copper, Oxazolidinone, Palladium, Process chemistry


This account depicts strategies adopted during the development of the κ-opioid receptor agonist CJ-15,161. While the original discovery synthesis was enabled for scale-up, concomitant process research aimed at identifying a novel and more efficient route was undertaken. In the former case, an efficient four-step sequence has been developed, where the process features four consecutive regioselective and stereospecific inversions at a single aziridinium stereogenic center, which leads to overall retention of stereochemistry in a single operation. The search for novel routes has also resulted in two converging methods involving efficient intermolecular N-arylation strategies. The first approach involves Pd-catalyzed intermolecular N-arylation of an appropriately functionalized diamine, obtained from the precursor α-amino acids or, more conveniently, from the corresponding 1,2-amino alcohols. The second approach exploits efficient intermolecular N-arylation of oxazolidinones using catalytic copper in the presence of a bidentate ligand leading to a straightforward and practical synthesis of CJ-15,161.






Scientific Articles

How to Cite

B. M. Andresen, B. C. Vanderplas, J. L. Tucker, J. E. Sieser, M. Riou, T. M. Makowski, J. M. Hawkins, M. Girardin, A. Ghosh, K. Dupont-Gaudet, N. M. Do, K. M. DeVries, M. Couturier, S. Caron, T. J. Watson, Chimia 2006, 60, 554, DOI: 10.2533/chimia.2006.554.