反应详情

温度

100 °C

To a suspension of 3-bromo-2-(o-tolyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine (0.06 g, 1 eq.) in a mixture of toluene (0.5 mL), ethanol (0.5 mL), and saturated sodium bicarbonate (0.1 mL) was added tert-butyl (1-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate (0.088 g, 1.5 eq.). The reaction was degassed (nitrogen) for 5 minutes and tetrakis(triphenylphosphine)palladium(0) added (0.017 g). The reaction was again degassed for 5 minutes and stirred at 100° C. overnight. The reaction mixture was cooled to room temperature and poured onto water (30 mL). The aqueous phase was extracted with dichloromethane (2×30 mL) and the organic extracts were combined and washed with water (1×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (5% ethyl acetate in dichloromethane) gave tert-butyl (1-(2-fluoro-4-(2-(o-tolyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepin-3-yl)phenyl)cyclobutyl)carbamate (0.133 g, 40%). M.p.: 138-140° C.; 1H NMR (DMSO-d6) 400 MHz δ 8.63 (s, 1H), 8.13 (d, J=4.4 Hz, 1H), 7.91 (d, J=7.6 Hz, 1H), 7.37-7.26 (m, 2H), 7.25-7.13 (m, 5H), 7.08 (t, J=7.4 Hz, 1H), 6.95 (bs. S, 1H), 6.74 (br. S, 1H), 6.69-6.63 (m, 2H), 2.42-2.28 (m, 4H), 2.08 (s, 3H), 2.04-1.94 (m, 1H), 1.76-1.64 (m, 1H), 1.34-1.10 (m, 9H, rotamers from BOC group); LCMS: 588 [M+H].

1. customThe reaction was degassed (nitrogen) for 5 minutes
2. additiontetrakis(triphenylphosphine)palladium(0) added (0.017 g)
3. customThe reaction was again degassed for 5 minutes
4. temperatureThe reaction mixture was cooled to room temperature
5. additionpoured onto water (30 mL)
6. extractionThe aqueous phase was extracted with dichloromethane (2×30 mL)
7. washwashed with water (1×50 mL), brine (1×50 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customPurification by column chromatography (5% ethyl acetate in dichloromethane)