反应详情

温度

120 °C

To (3-amino-2-fluoro-phenyl)-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (22, 1.080 g, 3.232 mmol) in a vial, N,N-dimethylacetamide (2.90 mL, 31.2 mmol) was added. The suspension was degassed by bubbling with argon and zinc powder (0.032 g, 0.48 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.0568 g, 0.102 mmol), zinc cyanide (0.223 g, 1.90 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.053 g, 0.052 mmol) were added at room temperature under argon. The mixture was heated to 120° C., resulting in most of the solid dissolving, and the mixture was heated at 120° C. for 2 hours, then cooled to 100° C. and 8 mL of water was added and the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate and saturated sodium chloride in water. The organic layer was washed with water and brine, then dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was suspended in acetonitrile and sonicated for 30 minutes, after which the precipitated material was collected by filtration to provide the desired compound as a tan solid (23, 613 mg). Additional material was recovered from the filtrate by silica gel chromatography eluting with ethyl acetate and hexanes, the appropriate fractions were combined and the solvent removed to provide an additional 42 mg. MS (ESI) [M+H+]+=280.9.

1. customThe suspension was degassed
2. additionwere added at room temperature under argon
3. customresulting in most of the solid
4. dissolutiondissolving
5. temperaturethe mixture was heated at 120° C. for 2 hours
6. temperaturecooled to 100° C.
7. temperaturethe reaction mixture cooled to room temperature
8. extractionThe reaction mixture was extracted with ethyl acetate and saturated sodium chloride in water
9. washThe organic layer was washed with water and brine
10. dry with materialdried with magnesium sulfate
11. filtrationfiltered
12. concentrationthe filtrate concentrated under vacuum
13. customsonicated for 30 minutes
14. filtrationafter which the precipitated material was collected by filtration