Process for the purification of neuromuscular blocking agents

摘要

A process for the preparation of neuromuscular blocking agents with isoquinoline structure, such as atracurium besylate, doxacurium chloride, mivacurium chloride and gantacurium chloride, by chromatographic purification of their mixtures of isomers using a silica modified by treatment with a tertiary amine of formula NR₁R₂R₃ or a corresponding quaternary ammonium compound N⁺R₁R₂R₃R₄X⁻ wherein R₁, R₂, R₃ and R₄, the same or different, are linear or branched C₁-C₄ alkyl groups or —CH₂—Ar groups or two among R₁, R₂, R₃ and R₄ form a 5- or 6-membered cycle, optionally substituted with a —CH₂—Ar group or condensed with an Ar group, Ar being an aryl optionally substituted with one or more electrodonating groups, and X⁻ being a suitable anion, is described.