反应详情

温度

90 °C

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 2,4-difluorophenol (0.229 g, 1.76 mmol). After 10 min, a clear/colorless solution resulted. 2-(2-Chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.075 g, 0.252 mmol) was added and the reaction became dark red. The reaction was sealed and heated to 90° C. for 4 h, then cooled to RT and stirred overnight. The reaction was cooled and partitioned between saturated aq. NH4Cl and EtOAc. The organic layer was washed with saturated aq. NaHCO3 (1×), water (1×), saturated aq. NaCl (1×), and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography using 0-50% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford 2-(2-(2,4-difluorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.036 g, 0.092 mmol, 37% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.99 (1H, br. s), 8.52 (1H, d, J=9.0 Hz), 8.09 (1H, dd, J=7.6, 1.4 Hz), 7.79-7.85 (1H, m), 7.55-7.69 (2H, m), 7.51 (1H, t, J=7.7 Hz), 7.47 (1H, d, J=9.0 Hz), 7.30 (1H, dddd, J=9.2, 7.9, 3.1, 1.5 Hz), 6.91-6.94 (1H, m), 6.90 (1H, d, J=2.3 Hz), 3.34-3.40 (2H, m), 2.52-2.57 (2H, m). m/z (ESI, +ve) 392.1 (M+H)+.

1. customa clear/colorless solution resulted
2. customThe reaction was sealed
3. temperaturecooled to RT
4. temperatureThe reaction was cooled
5. custompartitioned between saturated aq. NH4Cl and EtOAc
6. washThe organic layer was washed with saturated aq. NaHCO3 (1×), water (1×), saturated aq. NaCl (1×)
7. dry with materialthe organics were dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. additionThe material was treated with DCM
11. custompurified by silica gel chromatography
12. concentrationThe product-containing fractions were concentrated