反应详情

温度

80 °C

To a 10 mL round bottomed flask was added 1-(2-hydroxyethyl)-5-phenylpyrimidin-2(1H)-one (0.043 g, 0.20 mmol), 4-chloro-7-methoxyquinoline (0.042 g, 0.22 mmol), toluene (2.0 mL) and cesium carbonate (0.071 g, 0.22 mmol). The reaction was carefully evacuated and then backfilled with N2. This was repeated twice. Then racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (0.020 g, 0.050 mmol) and palladium(II) acetate (0.0089 g, 0.040 mmol) were added. The reaction was again carefully evacuated and then backfilled with N2. This was repeated twice. The mixture was then heated at 80° C. for 3 h. After cooling to room temperature, the mixture was poured into aq. NaHCO3 (50 mL) and extracted with EtOAc (100 mL). This produced a bad emulsion so the mixture was filtered through Celite. The Celite plug was eluted with 10% MeOH/CH2Cl2 and the aqueous phase was extracted with 25% iPrOH/CHCl3. The EtOAc extract, MeOH/CH2Cl2 eluent and the iPrOH/CHCl3 extracts were combined, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (0 to 1% MeOH (2M in NH3)/CH2Cl2 afforded 1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-5-phenylpyrimidin-2(1H)-one (0.023 g, 31% yield) as an off-white solid. MS (ESI, pos. ion.) m/z: 374 (MH+). Calc'd exact mass for C22H19N3O3: 373. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.87 (s, 3 H), 4.50 (t, J=4.8 Hz, 2 H), 4.59 (t, J=4.9 Hz, 2 H), 6.93 (d, J=5.3 Hz, 1 H), 7.02 (dd, J=9.2, 2.5 Hz, 1 H), 7.29 (d, J=2.5 Hz, 1 H), 7.37 (t, J=7.3 Hz, 1 H), 7.47 (t, J=7.6 Hz, 2 H), 7.60 (d, J=7.4 Hz, 2 H), 8.00 (d, J=9.2 Hz, 1 H), 8.63 (d, J=5.1 Hz, 1 H), 8.81 (d, J=3.5 Hz, 1 H), 8.97 (d, J=3.5 Hz, 1 H).

1. customThe reaction was carefully evacuated
2. customThe reaction was again carefully evacuated
3. temperatureAfter cooling to room temperature
4. additionthe mixture was poured into aq. NaHCO3 (50 mL)
5. extractionextracted with EtOAc (100 mL)
6. customThis produced a bad emulsion so the mixture
7. filtrationwas filtered through Celite
8. washThe Celite plug was eluted with 10% MeOH/CH2Cl2
9. extractionthe aqueous phase was extracted with 25% iPrOH/CHCl3
10. extractionThe EtOAc extract
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated onto silica
13. customPurification by silica gel chromatography (0 to 1% MeOH (2M in NH3)/CH2Cl2