反应详情

To a suspension of N-[2-(2,6-dioxo(3-piperidyl))-1,3-dioxoisoindolin-4-yl]-2-chloroacetamide (0.95 g, 2.72 mmol) in THF (30 ml) was added sodium iodide (0.41 g, 2.72 mmol) and 2M methyl amine in THF (4.08 ml, 8.15 mmol). The mixture was stirred at room temperature for 5 hours. The solvent was evaporated in vacuo leaving a white solid. The solid was slurried in ethyl acetate (200 ml) for 2 h. The suspension was then washed with water (3×100 ml), brine (100 ml), and dried (MgSO4). The solvent was evaporated in vacuo leaving an off-white solid. The solid was dissolved in acetonitrile (20 ml) and to this solution was added 2M HCl in ether (2 ml). The mixture was stirred for 1 h and the solvent evaporated in vacuo. The residue was slurried in ethyl acetate for 3 h and filtered to give an off-white solid. The solid was dissolved in water (40 ml) and washed with ethyl acetate 2×50 ml). The pH of the aqueous portion was adjusted to 11-12 by dropwise addition of saturated aqueous sodium carbonate. The aqueous mixture was washed with ethyl acetate (3×100 ml). The combined ethyl acetate extracts were washed with brine (100 ml), and dried (MgSO4). The solvent was evaporated in vacuo leaving a white solid. The solid was dissolved in acetonitrile (15 ml) and 2M HCl in ether (2 ml) was added to the solution. The mixture was stirred for 1 h and the solvent was evaporated in vacuo leaving a white solid. The solid was slurried in diethyl ether (20 ml) and filtered to give 0.18 g (17%) of product as a white solid: mp 228-230° C.; 1H NMR (DMSO-d6) d 11.13 (s, 1H), 10.50 (s, 1H), 9.35 (bs, 2H), 8.28-8.21 (m, 1H), 7.93-7.63 (m, 2H), 5.15 (dd, J=5.1 and 12.6 Hz, 1H), 4.09 (s, 2H), 3.03-2.85 (m, 1H), 2.63-2.47 (m, 5H), 2.10-2.05 (m, 1H); 13C NMR (DMSO-d6) d 171.99, 169.03, 166.35, 166.07, 164.75, 135.63, 134.46, 131.56, 127.45, 119.14, 118.85, 49.56, 48.82, 32.49, 30.59, 21.69; Anal. Calcd. For C16H17ClN4O5: C, 48.99; H, 4.70; N, 14.28. Found: C, 48.82; H, 4.72; N, 14.02+0.64H2O.

1. customThe solvent was evaporated in vacuo
2. customleaving a white solid
3. washThe suspension was then washed with water (3×100 ml), brine (100 ml)
4. dry with materialdried (MgSO4)
5. customThe solvent was evaporated in vacuo
6. customleaving an off-white solid
7. stirringThe mixture was stirred for 1 h
8. customthe solvent evaporated in vacuo
9. waitThe residue was slurried in ethyl acetate for 3 h
10. filtrationfiltered
11. customto give an off-white solid
12. washwashed with ethyl acetate 2×50 ml)
13. additionThe pH of the aqueous portion was adjusted to 11-12 by dropwise addition of saturated aqueous sodium carbonate
14. washThe aqueous mixture was washed with ethyl acetate (3×100 ml)
15. washThe combined ethyl acetate extracts were washed with brine (100 ml)
16. dry with materialdried (MgSO4)
17. customThe solvent was evaporated in vacuo
18. customleaving a white solid
19. stirringThe mixture was stirred for 1 h
20. customthe solvent was evaporated in vacuo
21. customleaving a white solid
22. filtrationfiltered