反应详情

温度

150 °C

In a microwave vial, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (80 mg, 0.15 mmol) was dissolved in 1.5 mL of 1,4-dioxane and 0.35 mL of water. The solution was purged with Ar gas then 4-(trifluoromethyl)phenylboronic acid (31 mg, 0.165 mmol), palladium bis-(diphenylphosphino)ferrocene dichloride, dichloromethane complex (6.1 mg, 0.008 mmol) and potassium carbonate (62 mg, 0.45 mmol) were added. The reaction vessel was sealed and heated in a microwave reactor at 150° C. for 30 min. The reaction was cooled and water and ethyl acetate were added. The mixture was poured into ethyl acetate and sodium bicarbonate solution. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 60 mg (66%) of 2-(4-trifluoromethylphenyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide.

1. customThe solution was purged with Ar gas
2. customThe reaction vessel was sealed
3. temperatureThe reaction was cooled
4. customThe layers were separated
5. extractionthe aqueous layer was extracted twice more with ethyl acetate
6. washThe combined organic layers were washed with brine
7. dry with materialdried over sodium sulfate
8. customAfter evaporation
9. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)