2-(4-Cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoic acid → 2-(2,6-Dioxopiperidin-3-yl)-1-oxoisoindoline-4-carbonitrile

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Reaction Steps

A mixture of 2-(4-cyano-1-oxoisoindolin-2-yl)-4carbamoylbutanoic acid (0.6 g, 2.09 mmol) and 1,1-carbonyldiimidazole (0.44 g, 2.72 mmol) in acetonitrile (20 mL) was heated to reflux for 2 hours. The mixture was cooled to room temperature and filtered to give 2-(2,6-dioxo(3-piperidyl))-1-oxoisoindoline-4-carbonitrile (0.44 g, 83%) as a white solid: mp 312–314° C.; 1H NMR (DMSO-d6) δ 11.04 (s, 1H), 8.16 (d, J=7.0 Hz, 1H), 8.06 (d, J=7.1 Hz, 1H), 7.74 (t, J=7.7 Hz, 1H), 5.20–5.13 (dd, J=5.2 and 13.2 Hz, 1H), 4.69 (d, J=181.1 Hz, 1H), 4.57 (d, J=18.1 Hz, 1H), 2.97–2.85 (m, 1H), 2.64–2.45 (m, 2H), 2.05–1.97 (m, 1H); 13C NMR (DMSO-d6) δ 172.81, 170.69, 166.49, 145.36, 135.37, 132.85, 129.36, 127.91, 116.01, 107.09. 51.77, 46.72, 31.14, 22.22; Anal. Calced. For C14H11N3O3: C, 62.45; H, 4.12; N, 15.61. Found: C, 62.26; H, 4.10; N, 15.51.

Provenance & Evidence