反应详情

温度

100 °C

To a microwave vial were added 4-[4-bromo-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (55 mg, 0.072 mmol), 4-[4-bromo-2-(trifluoromethyl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (55 mg, 0.072 mmol), cesium carbonate (82 mg, 0.251 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (6.0 mg, 0.00735 mmol) and the mixture was purged with nitrogen. 1,4-Dioxane (1 mL) and water (0.5 mL) were added to the mixture which was heated overnight 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 with 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 sodium sulfate, and concentrated in vacuo to afford the title product as a tan solid (15 mg, 41%). MS(ES)+ m/e 497.2 [M+H]+.

1. customthe mixture was purged with nitrogen
2. addition1,4-Dioxane (1 mL) and water (0.5 mL) were added to the mixture which
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 with 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 sodium sulfate
13. concentrationconcentrated in vacuo