反应详情

To a solution of tert-butyl 5,6-bis(chloromethyl)pyridine-3-carboxylate (1.80 g, 6.52 mmol) in N,N-dimethylformamide (93.0 mL) was added 4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (1.80 g, 10.62 mmol), cesium carbonate (3.65 g, 11.21 mmol), and sodium bromide (0.671 g, 6.52 mmol). After 30 min, saturated aqueous sodium bicarbonate was added and the mixture was washed with ethyl acetate (3×). The combined organics were washed with water (3×), brine (3×) and were dried with magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→10% methanol dichloromethane) then a second purification by silica gel chromatography (100% dichloromethane→30% ethyl acetate dichloromethane) 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=373.2 (M+1).

1. washthe mixture was washed with ethyl acetate (3×)
2. washThe combined organics were washed with water (3×), brine (3×)
3. dry with materialwere dried with magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by silica gel chromatography (100% dichloromethane→10% methanol dichloromethane)
7. customa second purification by silica gel chromatography (100% dichloromethane→30% ethyl acetate dichloromethane)