Diphosgene → 8-Fluoro-4-(2-methoxyethyl)-3-oxo-3,4-dihydro-2H-quinoxaline-1-carboxylic acid 4-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylamide

Participants

Reaction Steps

To a solution of 5-fluoro-1-(2-methoxyethyl)-3,4-dihydro-1H-quinoxalin-2-one from Example 16A (100 mg, 0.44 mmol) in toluene (7.0 ml) were added trichloromethyl chloroformate (54 μl, 0.45mmol), diisopropylethylamine (81 μl, 0.45 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 (5.0 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 (145 mg, 0.44 mmol) in THF (5.0 ml) and diisopropylethylamine (81 μl, 0.45 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 90:10) to give an off-white solid; yield 200 mg, 78%.

Provenance & Evidence