反应详情

To a stirred solution of 3-(2-methoxy-ethylamino)-phthalic acid (8.38 mmol) in pyridine (40 ml) was added 3-amino-piperidine-2,6-dione hydrochloride (1.39 g, 8.42 mmol). The reaction mixture was heated to reflux for 5 hours. The solvent was evaporated in vacuo and the residue dissolved in methylene chloride (125 ml). The methylene chloride mixture was treated with Norit (2 g), washed with water (2×100 ml), 0.1N HCl (1×100 ml), brine (1×100 ml), and dried (MgSO4). The solvent was evaporated in vacuo and the residue (oil) crystallized from a minimal amount of ethanol to give a yellow solid that was purified by preparative HPLC to give 1.71 g (64%) of product as a yellow solid: mp 1.82-1,84° C.; 1H NMR (DMSO-d6) d 11.12 (s, 1H), 7.58 (t, J=7.7 Hz, 1H), 7.12 (d, J=8.5 Hz, 1H), 7.04 (d, J=6.9 Hz, 1H), 6.59 (bs, 1H), 5.07 (dd, J=4.7 and 12.1 Hz, 1H), 3.54-3.30 (m, 7H), 2.95-2.85 (m, 1H), 2.64-2.52 (m, 2H), 2.07-2.02 (m, 1H); 13C NMR (DMSO-d6) d 172.79, 170.06, 168.98, 167.27, 146.38, 136.21, 132.07, 117.33, 110.67, 109.24, 70.39, 58.12, 48.58, 41.50, 30.99, 22.15; Anal. Calcd. For C16H17N3O5: C, 58.00; H15.17; N, 12.68. Found: C, 58.06; H, 5.12; N, 12.76.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 5 hours
3. customThe solvent was evaporated in vacuo
4. dissolutionthe residue dissolved in methylene chloride (125 ml)
5. additionThe methylene chloride mixture was treated with Norit (2 g)
6. washwashed with water (2×100 ml), 0.1N HCl (1×100 ml), brine (1×100 ml)
7. dry with materialdried (MgSO4)
8. customThe solvent was evaporated in vacuo
9. customthe residue (oil) crystallized from a minimal amount of ethanol
10. customto give a yellow solid
11. customthat was purified by preparative HPLC