New Approaches to Improving Bendamustine Microractor Synthesis

Abstract

Introduction. The chlorination reaction in the synthesis of the substance of bendamustine hydrochloride is a complex process. The presence of active adverse reactions makes scaling difficult.

Aim. Improving the performance of the technology for producing bendamustine ethyl ester in a flow microreactor.

Materials and methods. A series of experiments was carried out to carry out the chlorination stage in the synthesis of bendamustine hydrochloride in a flow microreactor with various concentrations in the initial reagent solutions.

Results and discussion. Experimental work was carried out to increase the productivity of the technology for the preparation of bendamustine ethyl ester (4-{[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl}butanoic acid ethyl ester) by increasing the concentration of the starting reagents in the reaction mass. The conditions for conducting the chlorination reaction in the synthesis of bendamustine hydrochloride have been optimized, and possible ways to further increase productivity have been analyzed. The effect of changes in the concentration of reagents in the initial solutions and flow rates of reagent solutions on the final reaction product was studied.

Conclusion. The optimal concentrations of reagents in the initial solutions were selected, allowing to increase the productivity of the flow microreactor with a volume of 137 mL to an equivalent level of a 100 liter capacitive reactor.