反应详情

温度

40 °C

3,4-Dichlorobenzoic acid (0.30 g, 1.6 mmol) was dissolved in 10 mL DMF and CDI (0.30 g, 1.9 mmol) was added. The mixture was stirred at 40° C. for 1 hour, and then 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.50 g, 1.6 mmol) and triethylamine (0.31 g, 3.1 mmol) were added. After an additional 90 minutes stirring at 40° C., the mixture was cooled. The solvent was evaporated, and the residue was dissolved in 60 mL CH2Cl2, and this solution was washed with water (2×60 mL), dried (MgSO4), and evaporated. The residue was chromatographed using a methylene chloride-methanol gradient, eluting 0.49 g of the product with 98:2 methylene chloride-methanol, in 70% yield: mp 161-163° C.; 1H NMR (DMSO-d6) δ 2.06-2.09 (m, 1H), 2.51-2.58 (m, 2H), 2.84-2.91 (m, 1H), 4.94 (d, J=5.7 Hz, 2H), 5.17 (dd, J=12.6 Hz, d=5.3 Hz, 1H), 7.74-7.95 (m, 5H), 8.17 (d, J=1.9 Hz, 1H), 9.33 (t, J=5.7 Hz, 1H), 11.10 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.5, 48.9, 122.0, 127.2, 127.7, 129.3, 130.8, 131.3, 131.6, 133.3, 134.3, 134.9, 138.8, 164.4, 167.0, 167.5, 169.8, 172.8; Anal. calcd for C21H15Cl2N3O5: C, 54.80; H, 3.28; N, 9.13. Found: C, 54.85; H, 3.36; N, 8.95.

1. stirringAfter an additional 90 minutes stirring at 40° C.
2. temperaturethe mixture was cooled
3. customThe solvent was evaporated
4. dissolutionthe residue was dissolved in 60 mL CH2Cl2
5. washthis solution was washed with water (2×60 mL)
6. dry with materialdried (MgSO4)
7. customevaporated
8. customThe residue was chromatographed
9. washeluting 0.49 g of the product with 98:2 methylene chloride-methanol