反应详情

A 4 mL vial was charged with 6-fluoro-1H-quinolin-2-one (00.56 g, 0.34 mmol), dry DMF (2 mL) and NaH (60% in oil, 0.015 g, 0.34 mmol). The mixture was stirred at rt for 1 h under a N2 atmosphere, and thereafter 1-bromo-3-chloropropane (34 μl, 0.34 mmol) was added and the mixture was then shaken at rt for 20 h. The reaction was diluted with diethyl ether (25 mL) and washed with water (15 mL). The organic phase was washed with water (15 mL) and brine (15 mL), dried over Na2SO4, and concentrated under reduced pressure. The oily residue was diluted with CH3CN (2 mL) and KI (0.083 g, 0.50 mmol), K2CO3 (0.069 g, 0.50 mmol) and 4-butylpiperidine (0.048 g, 0.34 mmol) was added. The mixture was shaken at 50° C. for 72 h and then diluted with EtOAc (25 mL) and washed with water (15 mL). The water phase was extracted (2×25 mL) and the combined organic phase was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by cation-exchange CC followed by flash CC (SiO2; EtOAc/MeOH 4:1) to yield the title compound (0.034 g, 29%). 1H NMR (CD3OD) δ 7.90 (d, J=9.2 Hz, 1H), 7.69 (dd, J=4.0, 8.8 Hz, 1H), 7.50-7.41 (m, 2H), 6.72 (d, J=8.8 Hz, 1 H), 4.41 (t, J=6.8 Hz, 2H), 3.02-2.95 (m, 2H), 2.65-2.60 (m, 2 H), 2.19-2.08 (m, 2H), 1.91-1.82 (m, 4 H), 1.53-1.21 (m, 9H), 0.90 (t, J=7.0 Hz); 13C NMR (CD3OD) δ 169.9, 158.4 (d, J=242 Hz), 139.8 (d, J=3 Hz), 134.4 (d, J=2 Hz), 122.5 (d, J=9 Hz), 121.6, 119.9 (d, J=24 Hz), 116.8 (d, J=8 Hz), 113.9 (d=23 Hz), 54.4, 53.0, 40.1, 34.5, 34.1, 30.1, 28.7, 23.3, 22.6, 13.2; HPLC-MS (ammonium acetate) [M+H]+=345.3.

1. stirringthe mixture was then shaken at rt for 20 h
2. washwashed with water (15 mL)
3. washThe organic phase was washed with water (15 mL) and brine (15 mL)
4. dry with materialdried over Na2SO4
5. concentrationconcentrated under reduced pressure
6. additionwas added
7. stirringThe mixture was shaken at 50° C. for 72 h
8. washwashed with water (15 mL)
9. extractionThe water phase was extracted (2×25 mL)
10. dry with materialthe combined organic phase was dried over Na2SO4
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by cation-exchange CC