反应详情

温度

-75 °C

To a flask containing 6-bromo-2,4-dichloro-3-phenylquinoline (275 mg, 0.78 mmol, Intermediate 1: step c) was added THF (10 mL) to give a homogeneous clear solution. The solution was cooled in a dry ice—acetone bath and n-BuLi (2.5 M in hexanes, 0.28 mL, 0.7 mmol) was added which resulted in an immediate orange-brown homogeneous solution. After 2 minutes, a solution of 1-(2,4-dimethylthiazol-5-yl)-2-methylpropan-1-one (200 mg, 1.09 mmol, Intermediate 4: step b) in 3 mL THF was added. The reaction mixture was maintained at −75° C. for 5 minutes then the dry ice—acetone bath was replaced with a 0° C. ice-bath. After 20 minutes the ice-bath was removed and the mixture was stirred at room temperature for 20 minutes. The mixture was quenched after a total reaction time of 45 minutes with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (3×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (100% DCM increasing to 20% EtOAc/DCM) provided the title compound as a white amorphous solid. 1H NMR (500 MHz, CD2Cl2) δ 8.42 (d, J=1.9 Hz, 1H), 7.96 (d, J=8.8 Hz, 1H), 7.81 (dd, J=8.9, 2.1 Hz, 1H), 7.57-7.46 (m, 3H), 7.41-7.27 (m, 2H), 2.77 (p, J=6.6 Hz, 1H), 2.52 (s, 3H), 2.19 (s, 3H), 1.16 (d, J=6.7 Hz, 3H), 0.81 (d, J=6.7 Hz, 3H); MS (ESI): mass calcd. for C24H22Cl2N2OS, 456.1, m/z found 457.0 [M+H]+.

1. customto give a homogeneous clear solution
2. temperatureThe solution was cooled in a dry ice—acetone bath
3. customresulted in an immediate orange-brown homogeneous solution
4. customwas replaced with a 0° C.
5. customAfter 20 minutes the ice-bath was removed
6. customThe mixture was quenched after a total reaction time of 45 minutes with aqueous NH4Cl solution
7. extractionthe aqueous portion was extracted with EtOAc (3×50 mL)
8. washThe combined organics were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated to dryness