反应详情

N4-{[3-(4-Fluorophenyl)isoxazol-5-yl]methyl}-N2,N2-bis(4-methoxybenzyl)-5,6-dimethylpyridine-2,3,4-triamine (6.00 g, 10.6 mmol), triethyl orthoformate (2.6 mL, 16 mmol), concentrated hydrochloride acid (0.2 mL), and toluene (30 mL) were combined at heated at reflux for 24 hours. An analysis by HPLC indicated the reaction was incomplete. Therefore, pyridine hydrochloride (0.25 g) was added, and the reaction vessel was fitted with a Dean-Stark trap. The reaction was heated at reflux for an additional 1.8 days, and additional triethyl orthoformate (1 mL) was added and heating was resumed. After the reaction was heated for a total of three days, it was allowed to cool to room temperature, and concentrated under reduced pressure. The residue was dissolved in dichloromethane, and the resulting solution was washed sequentially with aqueous potassium carbonate, water, and brine; dried over magnesium sulfate; and filtered. The solution was purified by column chromatography on silica gel (eluting with 5% ethyl acetate in dichloromethane) to provide 2.0 g of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N,N-bis(4-methoxybenzyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine as a pale yellow solid.

1. temperatureat heated
2. temperatureat reflux for 24 hours
3. customthe reaction vessel was fitted with a Dean-Stark trap
4. temperatureThe reaction was heated
5. temperatureat reflux for an additional 1.8 days
6. temperatureheating
7. temperatureAfter the reaction was heated for a total of three days, it
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in dichloromethane
10. washthe resulting solution was washed sequentially with aqueous potassium carbonate, water, and brine
11. dry with materialdried over magnesium sulfate
12. filtrationand filtered
13. customThe solution was purified by column chromatography on silica gel (eluting with 5% ethyl acetate in dichloromethane)