反应详情

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.4 g, 2.9 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.6 g, 1.9 mmol) in acetonitrile (100 mL). The mixture was heated for 30 minutes, then cooled to room temperature. Cyclohexyl isocyanate (0.4 g, 2.9 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was filtered and the solid was stirred with water (25 mL) to give 0.9 g of crude product. The crude product was recrystallized from methanol to give 1-cyclohexyl-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.12 g, 16%) as a white solid: mp 309-311° C.; 1H NMR (DMSO-d6) δ 0.97-1.75 (m, 10H), 1.99-2.04 (m, 1H), 2.32-2.64 (m, 3H), 2.86-2.98 (m, 1H), 4.27-4.51 (m, 4H), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 5.86 (d, J=7.9 Hz, 1H), 6.26 (t, J=5.5 Hz, 1H, NH), 7.47-7.62 (m, 3H, Ar), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.64, 24.44, 25.29, 31.16, 33.32, 46.09, 47.50, 47.85, 51.47, 121.36, 128.18, 130.26, 131.61, 136.28, 139.77, 157.20, 168.09, 170.97, 172.82; Anal. calcd. for C21H26N4O4: C, 63.30; H, 6.58; N, 14.06. Found: C, 63.18; N, 6.58; N, 13.99.

1. temperatureThe mixture was heated for 30 minutes
2. filtrationThe mixture was filtered
3. stirringthe solid was stirred with water (25 mL)
4. customto give 0.9 g of crude product
5. customThe crude product was recrystallized from methanol