反应详情

A solution of N-(4-trifluoromethoxyphenyl) 3-aminothiophene-2-carboxamide (1 g, 3.31 mmol) and quinoline-4-carboxaldehyde (347 mg, 2.21 mmol) in trifluoroacetic acid:dichloromethane (1:1, 30 mL) was heated at reflux for 2 h under nitrogen. The reaction was cooled to RT and triethylsilane (0.71 mL, 4.42 mmol) was added. The resulting solution was then stirred at reflux for 16 h under nitrogen. After cooling to RT, the reaction mixture was evaporated under reduced pressure and the residue was partitioned between ethyl acetate (3×100 mL) and saturated sodium bicarbonate solution (50 mL). The organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (20-30% ethyl acetate in hexane) to give EXAMPLE 1 as a light yellow solid, mp: 168-170° C. 1H-NMR (400 MHz/CDCl3): δ=5.01 (d, J=6.2 Hz, 2H), 6.56 (d, J=5.4 Hz, 1 H), 7.12 (s, 1H), 7.22 (d, J=8.7 Hz, 2H), 7.25 (s, 1H), 7.44 (d, J=4.3 Hz, 1 H), 7.58 (d, J=9.0 Hz, 2H), 7.62 (t, J=8.2 Hz, 1H), 7.76 (t, J=8.3 Hz, 1H), 8.02 (d, J=7.5 Hz, 2H), 8.17 (d, J=8.3 Hz, 1H), 8.86 (d, J=4.5 Hz, 1H). MS (ES+): 444 [MH+]. 13C-NMR (400 MHz/CDCl3): δ=45.9, 101.4, 117.9, 118.9, 119.5, 121.9, 122.0, 122.6, 126.5, 127.2, 129.1, 129.7, 130.6, 136.8, 144.5, 145.4, 148.3, 150.7, 155.9, 163.8. Anal. Calcd for C22H16F3N3O2S: C, 59.59; H, 3.64; N, 9.48; F, 12.85; S, 7.23. Found: C, 59.59; H, 3.67; N, 9.46; F, 13.01; S, 7.23.

1. temperatureat reflux for 2 h under nitrogen
2. temperatureat reflux for 16 h under nitrogen
3. temperatureAfter cooling to RT
4. customthe reaction mixture was evaporated under reduced pressure
5. customthe residue was partitioned between ethyl acetate (3×100 mL) and saturated sodium bicarbonate solution (50 mL)
6. dry with materialThe organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel chromatography (20-30% ethyl acetate in hexane)
10. customto give EXAMPLE 1 as a light yellow solid, mp: 168-170° C