反应详情

温度

80 °C

A mixture of 5-Chloro-2-trifluoromethyl[1,8]naphthyridine (200 mg, 0.86 mmol) and hexamethylditin (178 μL, 282 mg, 0.86 mmol) in DME (5 mL) was degassed via three “freeze-thaw” cycles. Tetrakis(triphenylphosphine)palladium(0) (49.7 mg, 0.043 mmol) was added, and the mixture was degassed as before, then was heated under nitrogen at 80° C. overnight. 2-(6-Bromopyridin-2-yl)benzonitrile (126 mg, 0.48 mmol) was added and the mixture was degassed as before, then more tetrakis(triphenylphosphine)palladium(0) (49.7 mg, 0.043 mmol) was added, the mixture was degassed again, then was stirred at 80° C. under nitrogen overnight. Water (25 mL) and dichloromethane (15 mL) were added to the cooled mixture, and the aqueous layer was washed with more dichloromethane (2×15 mL). The combined organic layers were washed with saturated sodium chloride solution (1×25 mL) then were dried over magnesium sulfate and concentrated in vacuo. The residual material was purified by flash chromatography on silica gel, eluting with 10% to 40% ethyl acetate in dichloromethane, affording 2-[6-(7-trifluoromethyl[1,8]naphthyridin-4-yl)pyridin-2-yl]benzonitrile as a colourless solid, which was recrystallised from ethyl acetate/isohexane (44 mg, 24%). δH (400 MHz, CDCl3) 7.52-7.60 (1H, td, J 7.6 and 1.2), 7.71-7.77 (2H, m), 7.82 7.92 (5H, m), 8.12 (1H, t, J 7.8), 9.11 (1H, d, J 8.6), 9.35 (1H, d, J 4.3). m/z (ES+) 377 [MH]+.

1. customwas degassed via three “freeze-thaw” cycles
2. customthe mixture was degassed as before,
3. additionwas added
4. customthe mixture was degassed again
5. additionWater (25 mL) and dichloromethane (15 mL) were added to the cooled mixture
6. washthe aqueous layer was washed with more dichloromethane (2×15 mL)
7. washThe combined organic layers were washed with saturated sodium chloride solution (1×25 mL)
8. dry with materialthen were dried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. customThe residual material was purified by flash chromatography on silica gel
11. washeluting with 10% to 40% ethyl acetate in dichloromethane