反应详情

温度

130 °C

To 4-(5-allyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)-3-bromobenzonitrile (0.275 g, 0.76 mmol) is added DME (3.0 mL). To this solution is added aqueous 2M sodium carbonate (1.5 ml, 3.0 mmol) followed by 4-fluorophenylboronic acid (0.269 g, 1.92 mmol). This mixture is transferred to a microwave safe vial Tetrakis(triphenylphosphine) palladium(0) (0.04 g, 0.034 mmol) is added, and the vessel sealed. The mixture is stirred briefly (30 seconds) and place in a microwave for 25 minutes at 130° C. The vial is allowed to cool and unsealed. The mixture is extracted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The separated organic layer is concentrated in vacuo. The resulting material is subjected to two sequential chromatography procedures (1: Silica gel, 1:50 to 1:25 methanol:methylene chloride. 2: Reverse phase HPLC, gradient 10-95% Acetonitrile:Water, pH2, over 8 minutes) to give the product. MS (ESI) m/z 276 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.47-1.61 (m, 1H), 1.85-1.99 (m, 1H), 2.01-2.16 (m, 3H), 2.25-2.36 (m, 1H), 2.63 (t, 1H), 2.99 (d, J=16.4 Hz, 1H), 3.10 (dd, J=15.5, 5.7 Hz, 1H), 3.23-3.32 (m, 1H), 5.21-5.25 (m, 1H), 5.62-5.67 (m, 1H), 6.50 (s, 1H), 6.78 (s, 1H), 7.54-7.58 (m, 1H), 7.66-7.70 (m, 1H), 7.88 (s, 1H).

1. additionis added
2. customthe vessel sealed
3. temperatureto cool
4. extractionThe mixture is extracted with ethyl acetate
5. washwashed with saturated aqueous sodium bicarbonate
6. concentrationThe separated organic layer is concentrated in vacuo
7. customis subjected to two sequential chromatography procedures (1: Silica gel, 1:50 to 1:25 methanol:methylene chloride. 2: Reverse phase HPLC, gradient 10-95% Acetonitrile:Water, pH2, over 8 minutes)
8. customto give the product