Reaction Steps
A mixture of fusaric acid (0.36 g, 2.0 mmol) and thionyl chloride (10 mL) was heated to reflux for 1 hour. Excess thionyl chloride was removed under vacuum. To the acid chloride, was then added 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), THF (30 mL) and triethylamine (0.61 g, 6.0 mmol), and the resulting mixture was stirred at room temperature for 16 hours. The solvent was evaporated, and the crude residue was chromatographed using a methylene chloride-methanol gradient, eluting the product with 95:5 methylene chloride-methanol. This material was further purified by preparative HPLC, eluting with 1:1 acetonitrile-water, providing 0.58 g of the purified product in 64% yield: mp 137-139° C.; 1H NMR (DMSO-d6) δ 0.91 (t, J=7.3 Hz, 3H), 1.24-1.39 (m, 2H), 1.54-1.65 (m, 2H), 2.06-2.10 (m, 2H), 2.51-2.72 (m, 4H), 2.84-2.97 (m, 1H), 4.94 (d, J=6.4 Hz, 2H), 5.17 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 7.66-7.71 (m, 1H), 7.77-7.86 (m, 3H), 7.97 (d, J=8.0 Hz, 1H), 8.54 (d, J=1.7 Hz, 1H), 9.43 (t, J=6.4 Hz, 1H), 11.16 (s, 1H); 13C NMR (DMSO-d6) δ 13.7, 21.6, 22.0, 31.0, 31.7, 32.6, 38.5, 48.9, 121.8, 121.9, 127.2, 131.6, 133.0, 134.8, 137.3, 139.2, 141.2, 147.5, 148.5, 164.5, 167.0, 167.6, 169.9, 172.8; Anal. calcd for C24H24N4O5.0.3H2O: C, 63.51; H, 5.46; N, 12.34. Found: C, 63.52; H, 5.55; N, 12.05.
