反应详情

温度

0 °C

A solution of 4.92 g (11.58 mmol) of (5-[(2,6-difluoro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-ethyl-amine in 85 mL of anhydrous tetrahydrofuran was cooled to 0° C. using an ice/acetone bath. The reaction mixture was treated with 1.16 g (28.95 mmol) of sodium hydride and continued stirring at 0° C. for 30 minutes. After 30 minutes, 5.63 g (34.74 mmol) of 1,1′-carbonyldiimidazole was added and continued to stir at 0° C. for an additional 30 minutes. After 1 hour, the ice bath was removed and the reaction mixture was allowed to warm up to room temperature. The reaction mixture heated at reflux overnight under nitrogen atmosphere. Evaporated the tetrahydrofuran and partitioned the residue between dichloromethane and water. The aqueous layer was extracted one time with 250 mL dichloromethane. The dichloromethane extracts were combined, dried over sodium sulfate, filtered and evaporated. The crude product was purified using medium-pressure chromatography eluting with 2:1 hexanes/ethyl acetate to give 4.23 g (92%) of the title compound: mp 165° C.–168° C. MS (APCI) (m+1)/z 397.1.

1. waitAfter 30 minutes
2. stirringto stir at 0° C. for an additional 30 minutes
3. waitAfter 1 hour
4. customthe ice bath was removed
5. temperatureto warm up to room temperature
6. temperatureThe reaction mixture heated
7. temperatureat reflux overnight under nitrogen atmosphere
8. customEvaporated the tetrahydrofuran
9. custompartitioned the residue between dichloromethane and water
10. extractionThe aqueous layer was extracted one time with 250 mL dichloromethane
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. customevaporated
14. customThe crude product was purified
15. washeluting with 2:1 hexanes/ethyl acetate