反应详情

温度

80 °C

A mixture of 6-chloro-4-iodo-pyridin-3-ylamine (2.37 g, 9.31 mmol), 2-fluoro-5-bromopyridine-3-boronic acid (2.64 g, 12.0 mmol) and 1,1′-[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.76 g, 0.93 mmol) in acetonitrile (35 mL) and 1N aqueous potassium fluoride solution (35 mL) was degassed with nitrogen for 20 minutes. The reaction mixture was heated at 80° C. for 3 h, allowed to cool to ambient temperature then partitioned between ethyl acetate (100 mL) and water (75 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The resultant solid residue was triturated using 1:1 DCM/methanol, collected by filtration, washed with diethyl ether and ethyl acetate to afford the title compound as a tan solid (1.37 g, 49%). The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-40% ethyl acetate in pentane) to afford further title compound as a brown solid (0.73 g, 26%). 1H NMR (DMSO-D6, 300 MHz): 8.46 (dd, J=2.5, 1.3 Hz, 1H), 8.24 (dd, J=8.3, 2.5 Hz, 1H), 7.88 (s, 1H), 7.19 (s, 1H), 5.57 (s, 2H). LCMS (Method B): RT=3.21 min, M+H+=304.

1. customwas degassed with nitrogen for 20 minutes
2. temperatureto cool to ambient temperature
3. customthen partitioned between ethyl acetate (100 mL) and water (75 mL)
4. customThe organic layer was separated
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. customevaporated in vacuo
8. customThe resultant solid residue was triturated
9. filtrationcollected by filtration
10. washwashed with diethyl ether and ethyl acetate