反应详情

To a solution of 8-bromo-6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (0.168 g, 0.32 mmol, intermediate 53) in DMF (2.0 mL) under nitrogent (balloon) was added palladium acetate (0.072 g, 0.32 mmol), dppf (0.220 g, 0.40 mmol), triethylamine (0.080 g, 0.800 mmol), and methanol (2.0 mL). The nitrogen balloon was replaced with a carbon monoxide balloon and the reaction mixture was stirred at rt for 1 h, and at 80° C. for 15 h. After cooling to rt, the reaction mixture was diluted with EtOAc and filtered through a pad of silica gel. The filtrate was concentrated to dryness and the residue was purified by SiO2 column chromatography eluting with EtOAc in hexanes to provide the title compound. LC/MS: m/e 520.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 8.28 (1H, d, J=1.6 Hz), 7.94 (1H, dd, J=8.5, 1.8 Hz), 7.61 (1H, d, J=7.5 Hz), 7.13 (1H, d, J=7.6 Hz), 7.10 (2H, d, J=8.5 Hz), 6.99 (1H, s), 6.92 (2H, d, J=8.4 Hz), 6.80 (1H, m), 4.70-4.90 (2H, br), 3.95 (3H, s), 1.25 (9H, s).

1. waitat 80° C. for 15 h
2. temperatureAfter cooling to rt
3. filtrationfiltered through a pad of silica gel
4. concentrationThe filtrate was concentrated to dryness
5. customthe residue was purified by SiO2 column chromatography
6. washeluting with EtOAc in hexanes