反应详情

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in acetonitrile (60 mL), was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 2-pyridylacetic acid hydrochloride (0.4 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). The mixture was stirred at room temperature overnight then was concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL) and washed with water (3×40 mL) and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH/CH2Cl2 3:97) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-pyridinyl-2-yl-acetamide (0.7 g, 74%) as a white solid: mp 146-148° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=0.91 min. (96%); 1H NMR (DMSO-d6) δ 2.02-2.09 (m, 1H), 2.53-2.63 (m, 2H), 2.84-2.96 (m, 1H), 3.74 (s, 2H), 4.75 (d, J=5.9 Hz, 2H), 5.12-5.18 (dd, J=5.2 and 12.7 Hz, 1H), 7.24-7.37 (m, 2H), 7.71-7.85 (m, 4H), 8.50-8.52 (d, J=0.8 and 4.9 Hz, 1H), 8.74 (t, J=5.9 Hz, 1H), 11.14 (s, 1H); 13C NMR (DMSO-d6) δ 21.95, 30.91, 37.94, 44.77, 48.83, 121.81, 123.84, 127.07, 131.48, 133.23, 134.66, 136.52, 139.14, 148.92, 156.09, 166.93, 167.46, 169.65, 169.80, 172.73; Anal. Calcd. for C21H18N4O5: C, 62.07; H, 4.46; N, 13.79. Found: C, 61.74; H, 4.18; N, 13.41.

1. stirringThe mixture was stirred at room temperature overnight
2. concentrationthen was concentrated in vacuo
3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
4. washwashed with water (3×40 mL) and brine (40 mL)
5. dry with materialdried over MgSO4
6. customSolvent was removed in vacuo
7. customthe residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH/CH2Cl2 3:97)