Reaction Steps
A mixture of 6-methylpicolinic acid (0.27 g, 2.0 mmol) and CDI (0.39 g, 2.4 mmol) in DMF (25 mL) was stirred at ambient temperature under nitrogen for 1 hour. 4-Aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) were added, and the mixture was allowed to stir for 16 hours. The solvent was evaporated under vacuum, and the residue was purified by preparative HPLC, eluting with 45:55 acetonitrile-water, providing 0.34 g of the product in 54% yield: mp 197-199° C.; 1H NMR (DMSO-d6) δ 2.06-2.11 (m, 1H), 2.53-2.65 (m, 2H), 2.58 (s, 3H), 2.84-2.94 (m, 1H), 4.96 (d, J=6.3 Hz, 2H), 5.18 (dd, J=12.6 Hz, d=5.4 Hz, 1H), 7.49 (dd, J=6.8 Hz, J=1.9 Hz, 1H), 7.69 (dd, J=8.5 Hz, J=4.1 Hz, 1H), 7.79-7.93 (m, 4H), 9.36 (t, J=6.3 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 23.9, 30.9, 38.3, 48.9, 119.2, 121.9, 126.3, 127.2, 131.6, 133.0, 134.8, 137.9, 139.2, 149.0, 157.3, 164.5, 167.0, 167.6, 169.8, 172.8; Anal. calcd for C21H18N4O5.0.6H2O: C, 60.45; H, 4.63; N, 13.42. Found: C, 60.47; H, 4.53; N, 13.36.
