反应详情

温度

160 °C

In an 8 mL vial equipped with a stir bar was placed 5-(3′Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-2-fluoro-pyridine (P-456, 100 mg, 0.289 mmol), (2S,5S)-2,5-dimethyl-pyrrolidine (176 mg, 1.30 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (367 uL, 2.60 mmol). The mixture was heated to 160° C. for 3 hours and then cooled to room temperature. The reaction mixture was treated with water (4 mL) and 1M HCl (6 mL). The aqueous portion was extracted with dichloromethane (2×30 mL), the organic portions were combined, washed with brine (15 mL), dried (MgSO4) and concentrated. The crude material was purified by silica gel column chromatography utilizing 5% acetone/dichloromethane as the eluent to produce 10 mg of P-577 as a pale viscous oil. 1H NMR (400 MHz, DMSO-d6) δ 1.05 (d, J=6 Hz, 6H), 1.56-1.61 (m, 4H), 3.72 (s, 3H), 3.75 (s, 2H), 4.07-4.12 (m, 2H), 6.38 (d, J=9 Hz, 1H), 6.92 (d, J=8 Hz, 1H), 7.27-7.32 (m, 3H), 7.37 (s, 1H), 7.41-7.47 (m, 2H), 7.95 (d, J=2 Hz, 1H) ppm. MS (APCI+): 425.1 (M+1) LC-MS: 92%

1. customIn an 8 mL vial equipped with a stir bar
2. temperaturecooled to room temperature
3. extractionThe aqueous portion was extracted with dichloromethane (2×30 mL)
4. washwashed with brine (15 mL)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customThe crude material was purified by silica gel column chromatography
8. customto produce 10 mg of P-577 as a pale viscous oil