反应详情

To a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.4 g, 1.20 mmol) and 4-chlorophenylacetyl chloride (0.23 g, 1.20 mmol) in N,N-dimethylformamide (15 mL), was added triethylamine (0.34 mL, 2.40 mmol) at room temperature under nitrogen. After 2 h, the mixture was diluted with water (10 mL) and the product was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water (3×100 mL), dried (MgSO4) and concentrated in vacuo. The residue was triturated in acetonitrile (20 mL) for 2 h. The solids were isolated by filtration and washed with acetonitrile (10 mL) providing 2-(4-chloro-phenyl)-N-[2-(3-methyl-2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-acetamide as a white solid (0.24 g, 44% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 50/50 CH3CN/0.1% H3PO4, 1.87 min (96.81%); mp: 230-232° C.; 1H NMR (DMSO-d6) δ 1.67 (s, 3H), 1.81-1.95 (m, 1H), 2.52-2.82 (m, 3H), 3.50 (s, 2H), 4.37 (d, J=5.9 Hz, 2H), 4.52-4.74 (m, 2H), 7.25-7.44 (m, 6H), 7.57 (d, J=7.7 Hz, 1H), 8.67 (t, J=5.8 Hz, 1H), 10.85 (s, 1H); 13C NMR (DMSO-d6) δ 20.75, 27.81, 29.01, 41.49, 42.24, 47.60, 57.12, 121.78, 122.55, 127.00, 128.15, 130.92, 130.98, 131.14, 135.28, 142.33, 143.59, 166.91, 169.87, 172.43, 173.55; Anal Calcd for C23H22ClN3O4+0.3H2O: C, 62.04; H, 5.12; N, 9.44. Found: C, 61.98; H, 4.80; N, 9.17.

1. extractionthe product was extracted with ethyl acetate (3×50 mL)
2. washThe combined organic layers were washed with water (3×100 mL)
3. dry with materialdried (MgSO4)
4. concentrationconcentrated in vacuo
5. customThe residue was triturated in acetonitrile (20 mL) for 2 h
6. customThe solids were isolated by filtration
7. washwashed with acetonitrile (10 mL)