Sodium Hydroxide → HCID 11953000, compound

Participants

Reaction Steps

A solution of (3S)-1-(4-tert-Butoxycarbonyl-butyl)-3-(4-chloro-phenyl)-4-[(R)-1-(4-chloro-phenyl)-ethyl]-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]-diazepine-7-carboxylic acid (Example 33) (63 mg, 0.10 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (57 mg, 0.15 mmol), HOBT (20 mg, 0.15 mmol) N,N-diisopropylethylamine (70 μL, 0.4 mmol), ammonium chloride (11 mg, 0.2 mmol) in DMF (400 μL) was stirred at room temperature for 1 h. under argon atmosphere. After evaporation of the solvent, the residue was diluted with EtOAc (15 mL), washed with water (10 mL), dried (Na2SO4) then concentrated to dryness under reduced pressure. Chromatography on silica (EtOAc/hexanes, 1:1) afforded anoil (58 mg), which was dissolved in dichloromethane (1.5 mL) and TFA (0.5 mL). This solution was stirred at room temperature for 10 h, then evaporated to dryness. The residue was dissolved in ice-cold water (10 mL) and AcONa (100 mg)/AcOH (100 μL) were added. The solution was extracted with ether (3×20 mL), then the organic layer was dried (Na2SO4) and concentrated to dryness under reduced pressure. Purification by column chromatography (EtOAc/CH2Cl2/EtOH, 5:4:1) afforded a colorless oil, which was converted to its sodium salt with NaOH 1N in EtOH. Recrystallization from EtOH/ether yielded title compound (37 mg, 62%) as a white powder: Mass spectrum (LCMS, ESI pos.): Calcd for C29H27Cl2IN3O5: 567.13; found 568.0 (M+H).

Provenance & Evidence