Diphosgene → {1-[4-(5H,11H-Benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)-2-methylbenzylcarbamoyl]-8-fluoro-2,3-dihydro-1H-quinolin-4-ylidene}acetic acid ethyl ester

Participants

Reaction Steps

A mixture of (8-fluoro-2,3-dihydro-1H-quinolin-4-ylidene)acetic acid ethyl ester from Example 4A (50 mg, 0.21 mmol), trichioromethyl chloroformate (28 μl, 0.23 mmol), diisopropylethylamine (41 μl, 0.23 mmol) and a small spatula of activated carbon in toluene (2 ml) was heated at reflux for 2 h. After cooling, EtOAc was added and the mixture filtered through Celite® and evaporated. The residue was taken up in THF to which was added a solution of (4-aminomethyl-3-methylphenyl)-(5H,11H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-10-yl)methanone from Example G (77 mg, 0.23 mmol) and diisopropylethylamine (41 μl, 0.23 mmol) in dichloromethane (2 ml). The mixture was stirred for 18 h, evaporated and the residue was purified by flash chromatography on silica (EtOAC:pet ether, 20:80 to 50:50) to give a white solid, yield 4 mg (3%).

Provenance & Evidence