Reaction Steps
A heterogeneous mixture of 3-(4-aminomethyl-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.50 g, 1.6 mmol), 1-naphthyl isocyanate (0.26 g, 1.6 mmol), and triethylamine (4.9 g, 4.9 mmol) in 25 mL THF was stirred under nitrogen at ambient temperature for 18 hours. The solvent was removed under vacuum. The residue was triturated with 3% aqueous HCl (100 mL) for 1 hour and then filtered, and the filter was washed with additional 3% HCl. The resulting solid was dried, triturated with 30 mL refluxing acetone for 1 hour and filtered, and the filter was washed with additional hot acetone. The resulting solid was dried and then triturated with 30 mL refluxing acetonitrile, filtered, and dried, to provide 0.40 g of the product in 56% yield: 1H NMR (DMSO-d6) δ 2.00-2.09 (m, 1H), 2.35-2.42 (m, 1H), 2.57-2.63 (m, 1H), 2.86-2.98 (m, 1H), 4.44 (d, J=17.2 Hz, 1H), 4.46 (d, J=5.8 Hz, 2H), 4.58 (d, J=17.2 Hz, 1H), 5.16 (dd, J=13.1 Hz, J=5.1 Hz, 1H), 7.11 (t, J=5.8 Hz, 1H), 7.09-7.67 (m, 7H), 7.90 (dd, J=6.6 Hz, J=2.9 Hz, 1H), 7.95 (d, J=7.4 Hz, 1H), 8.09 (t, J=9.0 Hz, 1H), 8.66 (s, 1H), 11.03 (s, 1H); 13C NMR (DMSO-d6) δ 22.6, 31.2, 40.0, 46.2, 51.6, 117.0, 121.4, 121.6, 122.4, 125.5, 125.8, 125.9, 128.3, 128.4, 130.4, 131.7, 133.7, 134.9, 135.5, 140.0, 155.7, 168.1, 171.0, 172.8; Anal. calcd for C25H22N4O4: C, 67.86; H, 5.01; N, 12.66. Found: C, 67.64; H, 4.99; N, 12.28.
