反应详情

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.37 g, 1.00 mmol) and p-tolyl-isocyanate (0.13 g, 1.00 mmol) in acetonitrile (30 mL) at 0° C. was added TEA (0.20 g, 2.0 mmol) dropwise over 10 min. The mixture was stirred at ambient temperature for 1.5 h and then 10% aqueous HCl solution (30 mL) was added. The solid precipitate was filtered, washed with water (20 mL) and dried in vacuo providing 1-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-3-p-tolyl-urea as a white solid (0.19 g, 46% yield); mp 267-269° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.30 (99.66%); 1H NMR (DMSO-d6) δ 1.91-2.08 (m, 1H, CHH), 2.21 (s, 3H, CH3), 2.28-2.47 (m, 1H, CHH), 2.53-2.68 (m, 1H, CHH), 2.80-3.02 (m, 1H, CHH), 4.31 (d, 1H, CHH), 4.36-4.52 (m, 3H, CH2 and CHH), 5.11 (dd, J=4.8, 13.1 Hz, 1H, CH), 6.69 (t, 1H, NH), 7.02 (d, 2H, Ar), 7.29 (d, J=8.1 Hz, 2H, Ar), 7.42 (d, 1H, Ar), 7.51 (s, 1H, Ar), 7.69 (d, 1H, Ar), 8.52 (s, 1H, NH), 10.98 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.28, 22.49, 31.20, 42.76, 45.72, 47.12, 51.56, 117.84, 121.86, 122.91, 126.89, 129.01, 129.84, 130.27, 137.81, 142.38, 144.93, 155.28, 167.95, 170.99, 172.85; LCMS: MH=407; Anal. Calcd for C22H22N4O4: C, 65.01; H, 5.46; N, 13.78. Found: C, 64.75; H, 5.48; N, 13.66.

1. filtrationThe solid precipitate was filtered
2. washwashed with water (20 mL)
3. customdried in vacuo