反应详情

温度

80 °C

Amine 2b (750 mg, 3.1 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (920 mg, 3.1 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1f (620 mg, 3.1 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 1/petroleum ether 1). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 120 mg of a white solid. Yield=9% 1HNMR (DMSO, 200 MHz) δ 1.89 (4H, m), 3.20 (4H, m), 4.33 (2H, d, J=5.6 Hz), 4.60 (2H, s), 6.45 (1H, dd, J=8 Hz, J′=1.2 Hz), 6.79 (1H, t, J=8.4 Hz), 7.04 (1H, bs), 7.16 (1H, d), 7.23 (1H, t), 7.35 (1H, d), 7.72 (1H, dd, J=8.2 Hz, J′=1.4 Hz), 8.16 (1H, bs), 10.63 (1H, bs); [M+1] 435.1 (C21H21F3N4O3 requires 434.41).

1. additionwas added to the solution
2. customthen evaporated
3. dissolutionthe residue was dissolved in 5 ml of DMF
4. temperaturethe mixture was warmed at 80° C. for 8 hours
5. customThe solvent was evaporated
6. dissolutionthe crude was dissolved in AcOEt (30 ml)
7. washwashed with water (1×20 ml) and brine
8. dry with materialThe organic phase was dried over sodium sulfate
9. concentrationconcentrated under vacuum
10. customThe purification of the crude residue by chromatographic column