反应详情

温度

40 °C

A mixture of 5-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.97 g, 3.0 mmol), 3,4-dichlorophenyl isocyanate (0.56 g, 3.0 mmol) and N,N-diisopropylethylamine (1.05 mL, 6.00 mmol) in pyridine (20 mL) was stirred at 40° C. overnight. The reaction mixture was cooled to room temperature, and the solvent was removed under vacuum. The residue was suspended in a biphasic mixture of CH2Cl2 (150 mL) and water (150 mL) and stirred for 2 hours. The solid was filtered, washed with additional water (50 mL), and dried. The resulting solid was stirred in methanol (200 mL) at room temperature for 1 hour, filtered, and dried. This material was refluxed in methanol (2×200 mL) for 3 hours, filtered, and dried. The resulting solid was chromatographed using a methanol-CH2Cl2 (with 0.1% of triethylamine) gradient, eluting 0.23 g of the product at 7:93 methanol-CH2Cl2 (with 0.1% of triethylamine), in 16% yield; mp 290-292° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 10.50 (97.00%); 1H NMR (DMSO-d6) δ 2.03-2.07 (m, 1H), 2.56-2.62 (m, 2H), 2.82-2.94 (m, 1H), 4.47 (d, J=5.9 Hz, 2H), 5.15 (dd, J=12.6 Hz, J=5.4 Hz, 1H), 7.05 (t, J=6.1 Hz, 1H), 7.29 (dd, J=8.8 Hz, J=2.4 Hz, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.77-7.91 (m, 4H), 9.11 (s, 1H), 11.13 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 42.7, 49.0, 117.9, 118.9, 121.7, 122.4, 123.5, 129.7, 130.4, 130.9, 131.6, 133.3, 140.6, 148.4, 155.0, 167.0, 167.2, 169.8, 172.7; Anal. Calcd for C21H16N4O5Cl2+0.25H2O: C, 52.57; H, 3.47; N, 11.68. Found: C, 52.22; H, 3.25; N, 11.56.

1. temperatureThe reaction mixture was cooled to room temperature
2. customthe solvent was removed under vacuum
3. additionThe residue was suspended in a biphasic mixture of CH2Cl2 (150 mL) and water (150 mL)
4. stirringstirred for 2 hours
5. filtrationThe solid was filtered
6. washwashed with additional water (50 mL)
7. customdried
8. stirringThe resulting solid was stirred in methanol (200 mL) at room temperature for 1 hour
9. filtrationfiltered
10. customdried
11. temperatureThis material was refluxed in methanol (2×200 mL) for 3 hours
12. filtrationfiltered
13. customdried
14. customThe resulting solid was chromatographed
15. washeluting 0.23 g of the product at 7:93 methanol-CH2Cl2 (with 0.1% of triethylamine)