反应详情

温度

80 °C

Amine 2c (1 g, 3.8 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.13 g, 3.8 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 1e (425 mg, 2.6 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt). 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 530 mg of a white solid. Yield=45% 1HNMR (DMSO, 400 MHz) δ 1.56 (2H, bs), 1.69 (4H, bs), 4.55 (2H, d, J=5.6 Hz), 4.64 (2H, s), 6.64 (2H, dd, J=14 Hz, J′=7.6 Hz), 6.88 (1H, t, J=8 Hz), 7.32 (1H, s), 7.39 (2H, s), 8.64 (1H, t), 10.66 (1H, bs), 10.88 (1H, bs); [M+1] 449.2 (C22H23F3N4O3 requires 448.4).

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