Triethylamine → Pyrimidine-5-carboxylic acid [2-(2,6-dioxopiperidin-3-YL)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]amide

Participants

Reaction Steps

A mixture of pyrimidine-5-carboxylic acid (0.25 g, 2.0 mmol) and CDI (0.39 g, 2.4 mmol) in DMF (25 mL) was stirred at ambient temperature under nitrogen for 2 hours. 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 chromatographed using a methylene chloride-methanol gradient, eluting with 95:5 methylene chloride-methanol, providing 0.39 g of the product in 50% yield: mp>260° C.; 1H NMR (DMSO-d6) δ 2.05-2.10 (m, 1H), 2.53-2.65 (m, 2H), 2.83-2.91 (m, 1H), 4.98 (d, J=5.7 Hz, 2H), 5.18 (dd, J=12.4 Hz, d=5.4 Hz, 1H), 7.84 (s, 3H), 9.24 (s, 2H), 9.35 (s, 1H), 9.52 (t, J=5.7 Hz, 1H), 11.16 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.3, 48.9, 122.1, 127.3, 127.5, 131.6, 133.4, 134.9, 138.4, 156.0, 160.1, 163.5, 167.0, 167.5, 169.8, 172.8; Anal. calcd for C19H15N5O5.0.3H2O: C, 57.23; H, 3.94; N, 17.56. Found: C, 57.27; H, 3.71; N, 17.27.

Provenance & Evidence