反应详情

温度

100 °C

A solution of 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) in dioxane (1.5 mL) was treated with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (0.269 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (9.9 mg), and 2M aq potassium carbonate (0.733 mmol). The reaction mixture was purged with nitrogen, sealed, and stirred at 100° C. overnight. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH˜4 using 1N aq HCl and was extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The brown residue was purified by reverse phase HPLC (Gilson, Xbridge C-18:19×100 mm column; 25-55% acetonitrile/water+0.1% NH4OH). Product fractions were selected, combined and concentrated to dryness in vacuo to afford the title compound as a white amorphous solid (57 mg, 50% yield). MS(ES)+ m/e 447.2 [M+H]+.

1. customThe reaction mixture was purged with nitrogen
2. customsealed
3. temperatureThe reaction mixture was cooled to room temperature
4. additionwas diluted with water (50 mL)
5. extractionwas extracted with dichloromethane
6. dry with materialThe organic layer was dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe brown residue was purified by reverse phase HPLC (Gilson, Xbridge C-18:19×100 mm column; 25-55% acetonitrile/water+0.1% NH4OH)
10. concentrationconcentrated to dryness in vacuo