Diphosgene → 8-Fluoro-4-methyl-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

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Reaction Steps

To a solution of 5-fluoro-1-methyl-3,4-dihydro-1H-quinoxalin-2-one from Example 18A (72 mg, 0.40 mmol) in toluene (4.0 ml) were added trichloromethyl chloroformate (48 μl, 0.40 mmol), diisopropylethylamine (72 μl, 0.40 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 (3.0 ml) and added to a solution of (4-aminomethyl-3-methyl-phenyl)-(5H,11H-benzo[e]pyrrolo[ 1,2-a][1,4]diazepin-10-yl)methanone from Example G (119 mg, 0.36 mmol) in THF (5.0 ml) and diisopropylethylamine (72 μl, 0.40 mmol) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature, stirred for 1.5 h and evaporated in vacuo. The residue was purified by flash column chromatography on silica (eluant EtOAc:pet. ether 85:15) to give a pale yellow solid; yield 112 mg, 58%.

Provenance & Evidence