反应详情

NaH (461 mg, 11.54 mmol) was added portionwise to a solution of 3,5-difluoropyridin-4-ylamine (1.0 g, 7.69 mmol) in DMF (20 mL) at 0° C. under a nitrogen atmosphere. A solution of 2,6-dichloro-4-cyano-benzoyl chloride (1.98 g, 8.46 mmol) in DMF (15 mL) was then added whilst maintaining the internal temperature below 10° C. Stirring was continued for 1.5 hours. The reaction mixture was quenched by addition of a saturated solution of NH4Cl and partitioned between water and EtOAc. The aqueous phase was further extracted with EtOAc (×2) and the combined organic layers were washed with water, then with brine, dried (MgSO4) and concentrated under reduced pressure. The resultant residue was combined with the crude reaction mixture obtained following the same method starting from 3,5-difluoro-pyridin-4-ylamine (100 mg, 0.77 mmol) and purified by column chromatography on silica gel eluting with 0-50% EtOAc in cyclohexane to afford the title compound as an off-white solid (1.35 g, 49% yield). LCMS (Method D): RT=3.02 min, m/z: 328 [M+H+].

1. temperaturewhilst maintaining the internal temperature below 10° C
2. customThe reaction mixture was quenched by addition of a saturated solution of NH4Cl
3. custompartitioned between water and EtOAc
4. extractionThe aqueous phase was further extracted with EtOAc (×2)
5. washthe combined organic layers were washed with water
6. dry with materialwith brine, dried (MgSO4)
7. concentrationconcentrated under reduced pressure
8. customreaction mixture
9. customobtained
10. custompurified by column chromatography on silica gel eluting with 0-50% EtOAc in cyclohexane