A Novel Solid-Phase Synthetic Method for 1,4-Benzodiazepine-2,5-dione Derivatives

Abstract

Utilizing polymer-bound anthranilic acid derivatives 1, we were able to obtain the 1,4-benzodiazepine-2,5-dione derivatives 3 (R3 = H, R4 = H, MeO, Cl) through an unprecedented reaction sequence, reductive alkylation-N-protected amino acid coupling-deprotective cyclization, in 28-71% five-step overall isolated yields and 95-99% purities from Wang resin 4. Applying the novel protocol to the resin 2, the 7-benzamido-1,4-benzodiazepine-2,5-dione derivatives 3 (R1 = Bn, R4 = 7-BzNH) could be obtained in 19-42% seven- or eight-step overall isolated yields and 92-98% purities from AMEBA resin 7.