反应详情

Treat a 0° C. solution of (R)—N-benzyl-2-chloro-N-(2-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-ylamino)ethyl)propanamide (4.59 g, 10.4 mmol) in THF (104 mL) with NaH (60%, 625 mg, 15.6 mmol). Allow the reaction mixture to warm to ambient temperature and stir overnight. Cool the reaction to 0° C., and treat with additional NaH (60%, 208 mg, 5.20 mmol). Allow the reaction mixture to warm to ambient temperature and stir for 3 d. Partition the reaction mixture between brine and EtOAc. Separate the organic layer, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to provide the title compound as a white foam (3.64 g, 86%). ES/MS m/z 405.2 (M+1).

1. temperatureCool
2. customthe reaction to 0° C.
3. temperatureto warm to ambient temperature
4. stirringstir for 3 d
5. customPartition the reaction mixture between brine and EtOAc
6. customSeparate the organic layer
7. dry with materialdry over Na2SO4
8. filtrationfilter
9. concentrationconcentrate under reduced pressure
10. customPurify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)