Development of a Safe Process for Manufacturing of the Potent Anticancer Agent Melflufen Hydrochloride

Abstract

Melflufen is a novel cytostatic currently in phase III clinical trials for treatment of multiple myeloma. Development of a process suitable for production is described. The two key features of the novel method are late introduction of the alkylating pharmacophore and an improved method for formation of the bis-chloroethyl group.

Palladium Extraction Following Metal-Catalyzed Reactions: Recent Advances and Applications in the Pharmaceutical Industry

“…The use of silica-supported TMT for palladium removal has also been reported on an industrial scale by Magle Chemoswed and Recipharm, in the process development of Melflufen. 39 Following the hydrogenative nitro-reduction of intermediate 8, palladium levels were higher than the intended target, and a metal removal method was sought (Scheme 7). Treatment with 0.03 wt Si-TMT for 2 h at 35 °C demonstrated the best performance against nine other removal protocols, including thiol-and amine-functionalized silicas, as well as MP-TMT.…”

“…The use of silica-supported TMT for palladium removal has also been reported on an industrial scale by Magle Chemoswed and Recipharm, in the process development of Melflufen . Following the hydrogenative nitro-reduction of intermediate 8 , palladium levels were higher than the intended target, and a metal removal method was sought (Scheme ).…”