反应详情

To a solution of methyl 3,4-bis(bromomethyl)benzoate (5.0 g, 15.5 mmol) and 4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (5.3 g, 31.1 mmol) in N,N-dimethylformamide (150 mL) was added cesium carbonate (10.1 g, 31.1 mmol). After 10 min, water was added and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane) then a second silica gel purification (100% dichloromethane→>75% dichloromethane/EtOAc gave the title compound as a racemic mixture. Chiral separation of the individual enantiomers was accomplished by use of HPLC using a 10 cm ChiralPak® AD column (60% EtOH/hexanes with 0.1% diethylamine to give the title compound as the 1st eluting enantiomer. MS: m/z=330.1 (M+1).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe combined organic extracts were washed with water, brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane)
7. customa second silica gel purification (100% dichloromethane→>75% dichloromethane/EtOAc