反应详情

Dissolve 6-bromo-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-isoindolin-1-one (2.814 mmol, 1.014 g) in tetrahydrofuran (28 mL). Add 4-chloro-5-fluoro-pyrimidine (5.628 mmol, 518 μL) and cool to 0° C. Add potassium hexamethyldisilazide (4.502 mmol, 9 mL, 0.5 M in toluene) over 7 minutes and stir for 1 hour, then warm to ambient temperature and stir for 90 minutes. Pour into methyl-tert-butyl ether and aqueous 1 M HCl, add water and separate the layers. Wash with aqueous 1 N HCl, filter, wash with saturated aqueous sodium chloride, dry over magnesium sulfate, filter through a 2 cm pad of silica gel, and evaporate under reduced pressure to provide an oil. Purify on silica gel with 20-40% ethyl acetate/hexane to give the title compound as a foam (547 mg, 43%). ES/MS m/z: 456 (M+H).

1. stirringstir for 90 minutes
2. customseparate the layers
3. washWash with aqueous 1 N HCl
4. filtrationfilter
5. washwash with saturated aqueous sodium chloride
6. dry with materialdry over magnesium sulfate
7. filtrationfilter through a 2 cm pad of silica gel
8. customevaporate under reduced pressure
9. customto provide an oil
10. customPurify on silica gel with 20-40% ethyl acetate/hexane