Ruboxistaurin was a protein kinase C inhibitor that has undergone clinical evaluation for the treatment of microvascular complications of diabetes.  A key step in its synthesis is a macrocyclization to form the core 14-membered ring.            This poster describes the changes in solvent combination and addition strategy that resulted in doubling the throughput of the macrocyclization and its successful implementation in manufacturing.  Additional studies were performed to understand the mechanism, the variability in the kinetics, and the differing results between laboratory scale, 2-gallon experiments, and production results.

Doubling throughput in a macrocyclization while maintaining yield and quality:  Process improvement in Ruboxistaurin synthesis

246th National Meeting (2013)

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