Triethylamine → 2,5-Dichloro-N-[2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]nicotinamide

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Reaction Steps

A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), 2,5-dichloropyridine-3-carbonyl chloride (0.42 g, 2.0 mmol) and triethylamine (0.61 g, 6.0 mmol) in THF (30 mL) was stirred at ambient temperature under nitrogen for 18 hours. The mixture was evaporated, and the residue was chromatographed using a methylene chloride-methanol gradient, eluting with 95:5 methylene chloride-methanol, providing 0.50 g of the product (54% yield): mp>260° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.53-2.58 (m, 2H), 2.83-2.97 (m, 1H), 4.93 (d, J=5.7 Hz, 2H), 5.17 (dd, J=12.5 Hz, d=5.3 Hz, 1H), 7.82-7.91 (m, 3H), 8.28 (d, J=2.5 Hz, 1H), 8.61 (d, J=2.5 Hz, 1H), 9.35 (t, J=5.7 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.3, 48.9, 122.1, 127.3, 130.3, 131.6, 133.4, 134.9, 137.8, 138.0, 145.0, 148.8, 164.1, 166.9, 167.5, 169.8, 172.8; Anal. calcd for C20H14Cl2N4O5.0.2H2O: C, 51.68; H, 3.12; N, 12.05. Found: C, 51.64; H, 3.05; N, 11.98.

Provenance & Evidence