反应详情

温度

100 °C

To a microwave vial were added 4-(4-bromo-2,5-difluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (50 mg, 0.117 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (42.8 mg, 0.176 mmol), cesium carbonate (114 mg, 0.351 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (6.0 mg, 0.00735 mmol). The mixture was purged with nitrogen followed by the addition of 1,4-dioxane (1 mL) and water (0.5 mL). The suspension was heated overnight at 100° C. and analysis by LCMS indicated desired product formation and consumption of starting material. The mixture was filtered through a syringe filter and purified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA). The desired fractions were collected and added to a separatory funnel containing ethyl acetate. The aqueous phase was adjusted to pH˜6 with 1N aq HCl. The aqueous phase was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo to afford the title product as a white solid (25 mg, 46%). MS(ES)+ m/e 465.2 M+H]+.

1. customThe mixture was purged with nitrogen
2. additionfollowed by the addition of 1,4-dioxane (1 mL) and water (0.5 mL)
3. customdesired product formation and consumption of starting material
4. filtrationThe mixture was filtered through a syringe
5. filtrationfilter
6. custompurified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA)
7. customThe desired fractions were collected
8. additionadded to a separatory funnel
9. additioncontaining ethyl acetate
10. extractionThe aqueous phase was extracted with ethyl acetate (3×)
11. washthe combined organics were washed with brine
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo