Development of a Supply Route for the Synthesis of an iNOS Inhibitor: Complications of the Key SN2 Reaction

The original medicinal chemistry synthesis of an iNOS inhibitor presented several challenges that had to be overcome in order to constitute a supply route suitable for operation on a multikilo scale. The key step in the synthesis is an SN2 reaction that assembles the chiral carbon framework, but this reaction proved far more complex than we anticipated. Significant improvements were made to all stages. The modified route performed well over two pilot-plant campaigns and delivered over 250 kg of the active pharmaceutical ingredient (API).