反应详情

温度

100 °C

To a microwave vial were added 4-(4-bromo-5-chloro-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.124 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.16 mmol), cesium carbonate (0.37 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (0.0062 mmol). The mixture was purged with nitrogen and suspended in 1,4-dioxane (1 mL) and water (0.5 mL). The mixture was heated for 15 h at 100° C. 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 to afford the title product as an off-white solid (20 mg, 33%). MS(ES)+ m/e 492.2, 494.0 [M+H]+.

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