反应详情

温度

85 °C

A suspension of 5-bromo-3-formyl-1H-indole-6-carbonitrile (250 mg, 1.00 mmol), 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclobutanol (300 mg, 1.16 mmol) and 2 M aqueous potassium carbonate solution (1.26 mL, 2.51 mmol) in toluene (2.1 mL) and ethanol (1.25 mL) was degassed with nitrogen for 10 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (73.2 mg, 0.1 mmol) and heated to 85° C. for 1 hour, at which point the reaction mixture was treated with a solution of 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]cyclobutanol (40 mg) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30 mg) in DMF (0.6 mL). After 3.5 hours, the clear red reaction mixture was cooled to room temperature and poured into half-diluted ammonium chloride solution (100 mL). The product was extracted with ethyl acetate (6×70 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The crude product was purified using flash chromatograph eluting with heptanes/ethyl acetate (with 0.2% formic acid) (9:1 to 1:9) to give the title compound (223 mg, 70%) as an off-white solid. MS (ES−) 315.2 (M−H)−. 1H NMR (500 MHz, DMSO-d6) δ 12.62 (br. s., 1 H), 10.02 (s, 1 H), 8.59 (s, 1 H), 8.21 (s, 1 H), 8.13 (s, 1 H), 7.64 (d, J=8.3 Hz, 2 H), 7.56 (d, J=8.3 Hz, 2 H), 5.59 (s, 1 H), 2.48-2.43 (m, 2 H), 2.32-2.25 (m, 2H), 2.01-1.92 (m, 1H), 1.77-1.67 (m, 1H).

1. customwas degassed with nitrogen for 10 minutes
2. customthe clear red reaction mixture
3. temperaturewas cooled to room temperature
4. extractionThe product was extracted with ethyl acetate (6×70 mL)
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe crude product was purified
9. washeluting with heptanes/ethyl acetate (with 0.2% formic acid) (9:1 to 1:9)