反应详情

温度

60 °C

To a solution of NIS (6.31 g, 28.0 mmol) in anh DMF (100 mL) under Ar was added dry [3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutyl]methanol (6.67 g) dissolved in anh DMF (30 mL). The flask containing [3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclobutyl]methanol was rinsed with another portion of anh DMF (20 mL) and the rinse was added to the reaction mixture. The reaction was heated to 60° C. (rt→60° C.˜30 min) and the stirred at this temperature for 3 h. The mixture was then cooled to rt, partitioned between 1 M aq Na2S2O3 (60 mL), brine (60 mL) and DCM (160 mL). The aq layer was extracted with DCM (3×100 mL). The combined organics were dried (Na2SO4), concentrated under reduced pressure and purified by flash chromatography on SiO2 (0-8% MeOH in DCM) to provide a material, homogenous by UV on both TLC and HPLC, still containing DMF. The material was dissolved in DCM (200 mL) and washed with water (3×40 mL), dried (Na2SO4) and concentrated under reduced pressure to provide the title compound as a pale yellow solid; HPLC (polar5 min) 2.52 min; MS (ES+): m/z (rel. int.) 364.0 (100, M++1); 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J=4.8 Hz, 1H), 7.49 (d, J=4.8 Hz, 0.22 H, minor isomer), 7.29 (d, J=4.8 Hz, 1H), 7.28 (d, J=5.2 Hz, 0.23 H, minor isomer), 3.83-3.80 (m, 0.7H), 3.72-3.62 (m, 3H), 2.75-2.55 (m, 4H), 2.42-2.32 (m, 1-2H).

1. washwas rinsed with another portion of anh DMF (20 mL)
2. additionthe rinse was added to the reaction mixture
3. temperatureThe mixture was then cooled to rt
4. custompartitioned between 1 M aq Na2S2O3 (60 mL), brine (60 mL) and DCM (160 mL)
5. extractionThe aq layer was extracted with DCM (3×100 mL)
6. dry with materialThe combined organics were dried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. custompurified by flash chromatography on SiO2 (0-8% MeOH in DCM)
9. customto provide a material
10. washwashed with water (3×40 mL)
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated under reduced pressure