Diphosgene → {4-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylcarbamoyl]-5-fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl}acetic acid methyl ester

Participants

Reaction Steps

To a solution of (5-fluoro-2-oxo-3,4-dihydro-2H-quinoxalin-1-yl)acetic acid methyl ester from Example 17A (72 mg, 0.30 mmol) in toluene (5.0 ml) were added trichloromethyl chloroformate (36 μl, 0.30 mmol), diisopropylethylamine (54 μl, 0.30 mmol) and a spatula full of activated carbon. The mixture was heated at reflux for 2 h. The mixture was cooled to room temperature, filtered through Celite® and evaporated. The residue was taken up in THF (4.0 ml) and added to a solution of (4-aminomethyl-3-methylphenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)methanone from Example G (9 9mg, 0.30 mmol) in THF (4.0 ml) and diisopropylethylamine (54 μl, 0.30 mmol) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature, stirred for 18 h and evaporated in vacuo. The residue was purified by flash column chromatography on silica (eluant EtOAc:pet. ether 75:25) to give a white solid; yield 61 mg, 34%.

Provenance & Evidence