反应详情

温度

10 °C

1-(2-Chloro-4-cyclopropylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid (15 g, 54.0 mmol) and 4-amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate A)(11.30 g, 54.0 mmol) were slurried in EtOAc (150 mL). The reaction mixture was cooled to 10° C. and triethylamine (18.82 mL, 135 mmol) was added dropwise, followed by dropwise addition of T3P (50% w/w in EtOAc) (47.7 mL, 81 mmol) over 15 mins, maintaining a temperature <10° C. The reaction mixture was allowed to warm to RT and stirred for 2.5 hrs. The resulting mixture was quenched with sat. sodium bicarbonate (aq) (150 ml). The layers were separated and the organic layer was washed with sat. sodium bicarbonate (aq) (50 ml), water (150 ml) and brine (150 ml). The organic extracts were dried over MgSO4 and charcoal. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The crude material was slurried in ethyl acetate (335 ml) and heated to reflux with stirring. The hot mixture was filtered and the filtrate was seeded and at left to stand at room temperature overnight. The resulting crystalline solid was collected by filtration and dried under reduced pressure at 40° C. over 2 days to yield the title compound.

1. temperaturemaintaining a temperature <10° C
2. temperatureto warm to RT
3. customThe resulting mixture was quenched with sat. sodium bicarbonate (aq) (150 ml)
4. customThe layers were separated
5. washthe organic layer was washed with sat. sodium bicarbonate (aq) (50 ml), water (150 ml) and brine (150 ml)
6. dry with materialThe organic extracts were dried over MgSO4 and charcoal
7. filtrationThe desiccant was filtered off
8. concentrationthe filtrate was concentrated under reduced pressure
9. temperatureheated
10. temperatureto reflux
11. stirringwith stirring
12. filtrationThe hot mixture was filtered
13. waitat left
14. waitto stand at room temperature overnight
15. filtrationThe resulting crystalline solid was collected by filtration
16. customdried under reduced pressure at 40° C. over 2 days