反应详情

1,8-Diazabicyclo[5,4,0]undec-7-ene (0.98 g, 6.48 mmol) was added to stirred suspension of 4-(aminomethyl)-2-(2,6-dioxo(3-piperidyl))isoindoline-1,3-dione hydrochloride (0.6 g, 1.85 mmol) in CH3CN (50 ml). After stirring for 20 min, nicotinoyl chloride (0.41 g, 2.22 mmol) was added. The mixture was stirred at room temperature for 17 hours. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (70 ml). The CH2Cl2 solution was washed with H2O (30 ml), brine (30 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by flash chromatography (SiO2, CH2Cl2:CH3OH 97.5:2.5) to give N-{[(2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]methyl}-3-pyridylcarboxamide (0.47 g, 64%) as a white solid: mp 148–151° C.; 1H NMR (DMSO-d6) δ d 11.16 (s, 1H), 9.36 (t, J=5.6 Hz, 1H), 9.09 (d, J=1.25 Hz, 1H), 8.75–8.73 (m, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.84–7.76 (m, 3H), 7.57–7.52 (m, 1H), 5.22–5.15 (dd, J=5.4 and 12.7 Hz, 1H), 4.96 (d, J=5.6 Hz, 2H), 2.92–2.85 (m, 1H), 2.65–2.50 (m, 2H), 2.11–2.06 (m, 1H); 13C NMR (DMSO-d6) δ d 172.72, 169.80, 167.51, 166.94, 165.23, 152.02, 148.44, 138.86, 135.10, 134.83, 133.20, 131.55, 129.48, 127.20, 123.49, 121.95, 48.89, 38.33, 30.93, 21.98; Anal. Calcd. For C20H16N4O5+0.28 H2O: C, 60.45; H, 4.20; N, 14.10. Found: C, 60.29; H, 4.28; N, 13.82.

1. stirringAfter stirring for 20 min
2. stirringThe mixture was stirred at room temperature for 17 hours
3. customThe solvent was removed in vacuo
4. dissolutionthe residue was dissolved in CH2Cl2 (70 ml)
5. washThe CH2Cl2 solution was washed with H2O (30 ml), brine (30 ml)
6. dry with materialdried (MgSO4)
7. customThe solvent was removed in vacuo
8. customthe residue was purified by flash chromatography (SiO2, CH2Cl2:CH3OH 97.5:2.5)