Solid-Phase Synthesis of Benzodiazepine Derivatives

A novel synthetic protocol for 1,4-benzodiazepine-2,5-diones starting with resin-bound anthranilic acid derivatives 2 or 6 is described. Thus, the resin-supported compounds 2 and 6 were prepared from Wang resin 1 and AMEBA resin 5, respectively. The polymeric ­anthranilic acids 2 and 6 were condensed with N-Fmoc-amino acids. The resulting anilides 3 (from 2) were treated with 20% piperidine-DMF to give the 1,4-benzodiazepine-2,5-dion derivatives 4a-o in 28-71% yield with 92-98% purity. The anthranilic resin 6 gave 7-benzamido-1,4-benzodi­azepine-2,5-dion derivatives 4p-u in 19-42% yield with 92-98% purity a via resin-cleavage step.