3-Aminopiperidine-2,6-dione hydrochloride → 2-(2,6-Dioxo-3-piperidyl)-4-(2-methoxyethylamino)isoindoline-1,3-dione

Participants

Reaction Steps

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.

Provenance & Evidence