反应详情

温度

100 °C

Into a 5 mL microwaveable vial was placed 4-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.244 mmol), bis(pinacolato)diboron (0.244 mmol), potassium acetate (0.977 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (0.024 mmol), and 1,4-dioxane (2 mL). The vial was capped and the contents were purged with nitrogen. The solution stirred at 100° C. for 16 h. LCMS analysis displayed boronic ester intermediate present (boronic ester cleavage to acid also observed on LCMS) as well as a small amount of bromide starting material. The reaction was cooled to room temperature. Added to the vial was 2-bromo-6-fluoronaphthalene (0.244 mmol) and 2M aq potassium carbonate (1 mL). The vial was capped, purged with nitrogen, and stirred at 100° C. for 1 h. The solution was cooled to room temperature, whereby the dioxane layer separated from the aqueous layer. The dioxane layer was removed via pipette and was passed through a plug of celite and sodium sulfate. The plug was washed with dioxane (2 mL). All dioxane filtrates were combined and concentrated in vacuo. Reverse phase HPLC (30-80% acetonitrile/water+0.1% NH4OH) was utilized in purifying the title compound (21 mg, 17%). MS(ES)+ m/e 475.1 [M+H]+.

1. customThe vial was capped
2. customthe contents were purged with nitrogen
3. temperatureThe reaction was cooled to room temperature
4. additionAdded to the vial
5. customThe vial was capped
6. custompurged with nitrogen
7. stirringstirred at 100° C. for 1 h
8. temperatureThe solution was cooled to room temperature
9. customwhereby the dioxane layer separated from the aqueous layer
10. customThe dioxane layer was removed via pipette
11. washThe plug was washed with dioxane (2 mL)
12. concentrationconcentrated in vacuo
13. customin purifying the title compound (21 mg, 17%)