反应详情

温度

50 °C

A flask was charged with 2,6-dichloropyrimidin-4-amine (10.0 g, 61.0 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (Preparation E; 29.7 g, 91.5 mmol), and K2CO3 (25.3 g, 183 mmol) in dioxane (40 mL) before 300 mL of dioxane and 11 mL of water were added to the reaction mixture. The reaction mixture was then purged with argon for 30 minutes before tetrakis(triphenylphosphine)palladium (0) (3.52 g, 3.05 mmol) was added in one portion to the reaction which was then purged with argon for another 30 minutes. The reaction mixture was then sealed and heated at 50° C. overnight. The reaction mixture was cooled to ambient temperature and partitioned between ethyl acetate (300 mL) and aqueous saturated sodium bicarbonate (300 mL). The aqueous layer was then extracted with ethyl acetate twice more and separated. The organic layers were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexanes to afford 6-chloro-2-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-4-yl)pyrimidin-4-amine (5.00 g, 15.3 mmol, 25.2% yield). MS (apci) m/z=326.1 (M+H). Structure and regioisomer confirmed by observed nOe.

1. additionwere added to the reaction mixture
2. additionwas added in one portion to the reaction which
3. customwas then purged with argon for another 30 minutes
4. customThe reaction mixture was then sealed
5. temperatureThe reaction mixture was cooled to ambient temperature
6. custompartitioned between ethyl acetate (300 mL) and aqueous saturated sodium bicarbonate (300 mL)
7. extractionThe aqueous layer was then extracted with ethyl acetate twice more
8. customseparated
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe resulting residue was purified by silica gel column chromatography
13. washeluting with 20-100% ethyl acetate in hexanes