A research group from Nippon Soda and Active Pharma has announced the development of a synthesis process for the antirheumatic drug iguratimod using a continuous-flow method and an NHC catalyst immobilized on polystyrene resin. The results have been published in ACS Sustainable Chemistry & Engineering.
Nippon Soda and Active Pharma, working with researchers at the University of Tokyo, have announced the development of a continuous-flow synthesis process using an immobilized catalyst as a sustainable method for synthesizing the antirheumatic drug iguratimod. The results have been published in the international chemistry journal ACS Sustainable Chemistry & Engineering.
The study used an NHC catalyst immobilized on polystyrene resin and adopted a flow method in which the reaction proceeds continuously. In experiments, approximately 1.8 g of an iguratimod precursor was obtained stably during 24 hours of continuous operation, while the reaction conditions were controlled in real time using inline NMR.
The work reportedly required only acid washing, N-formylation and recrystallization for downstream processing, and achieved an overall yield of approximately 75% from the starting materials. The results are described as demonstrating the effectiveness of the process for manufacturing pharmaceutical active ingredients.
The study was conducted under a technology partnership concluded in 2023 between Nippon Soda and the Mitani Sangyo Group for the practical application and commercialization of continuous-flow methods. Future work is expected to focus on extending catalyst life, scaling up the process and applying it to other pharmaceuticals and active ingredients.