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温度

0 °C

To a solution of oxolan-3-ol (175.0 mg, 1.99 mmol) in anhydrous DMF (3 mL) was added NaH (66.0 mg, 1.65 mmol, 60% in mineral oil) at 0° C. and then stirred at 0° C. for 0.5 hrs. 4-(2-fluoro-5-methylsulfonylphenyl)-2-methylisoquinolin-1-one (110.0 mg, 0.33 mmol) was added. The mixture was stirred at 0° C. for 0.5 h and then at r.t. for 3 hrs. It was then quenched with aqueous sat. NH4Cl (20 mL) and extracted with EA (20 mL×3). The combined organic layers were washed with brine (40 mL), dried over Na2SO4, and concentrated under reduced pressure to afford a crude product which was purified by prep-HPLC to give the title compound (62.0 mg, 39.7%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.51 (d, J=7.6 Hz, 1H), 8.00 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.89 (d, J=2.4 Hz, 1H), 7.58-7.51 (m, 2H), 7.11-7.03 (m, 3H), 5.01-4.98 (m, 1H), 3.97 (dd, J1=10.4 Hz, J2=4.8 Hz, 1H), 3.76-3.70 (m, 2H), 3.67 (s, 3H), 3.61-3.42 (m, 1H), 3.11 (s, 3H), 2.18-1.88 (m, 2H). LCMS (M+H)+=400.0 (M+1)+

1. stirringThe mixture was stirred at 0° C. for 0.5 h
2. waitat r.t. for 3 hrs
3. customIt was then quenched with aqueous sat. NH4Cl (20 mL)
4. extractionextracted with EA (20 mL×3)
5. washThe combined organic layers were washed with brine (40 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customto afford a crude product which
9. customwas purified by prep-HPLC