反应详情

Under a nitrogen atmosphere, 2-chloro-N-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-5,6-dimethyl-3-nitropyridin-4-amine (25.00 g, 66.35 mmol), toluene (250 mL), triethylamine (11.1 mL, 79.6 mmol), and N,N-bis(4-methoxybenzyl)amine (18.8 g, 73.0 mmol) were combined and heated at reflux for three days. The volatiles were removed under reduced pressure, and the residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate. The ethyl acetate layer was separated and concentrated under reduced pressure. The residue was dissolved in dichloromethane, and the resulting solution was washed sequentially with water and brine. The combined aqueous fractions were extracted with ethyl acetate. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude solid was triturated with ethanol, isolated by filtration, and washed with diethyl ether to provide 37.29 g of N4-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N2,N2-bis(4-methoxybenzyl)-5,6-dimethyl-3-nitropyridin-2,4-diamine as an orange solid.

1. temperatureheated
2. temperatureat reflux for three days
3. customThe volatiles were removed under reduced pressure
4. customthe residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate
5. customThe ethyl acetate layer was separated
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in dichloromethane
8. washthe resulting solution was washed sequentially with water and brine
9. extractionThe combined aqueous fractions were extracted with ethyl acetate
10. dry with materialThe combined organic fractions were dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe crude solid was triturated with ethanol
14. customisolated by filtration
15. washwashed with diethyl ether