反应详情

温度

80 °C

Amine 2b (289 mg, 1.2 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (356 mg, 1.2 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 1b (180 mg, 1.2 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 100 mg of a white solid. Yield=20% 1HNMR (DMSO, 200 MHz) δ 1.94 (4H, m), 3.23 (4H, m), 4.67 (2H, d, J=5.6 Hz), 6.55 (2H, dd, J=8.8 Hz, J′=1.2 Hz), 7.05 (1H, t, J=8.2 Hz), 7.17 (2H, d, J=7.2 Hz), 7.46 (1H, d), 9.98 (1H, t), 11.53 (1H, bs), 11.80 (1H, bs); [M+1] 421.2 (C20H19F3N4O3 requires 420.39).

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