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A mixture of 4-methylsulphonylbenzoic acid (0.28 g, 1.4 mmol) and CDI (0.24 g, 1.5 mmol) was stirred in DMF (30 mL) at 40° C. for 4 hours. 3-(5-Aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.50 g, 1.4 mmol) was added and the mixture was stirred at 40° C. for 2 h. The mixture was quenched with 4% aqueous HCl (30 mL) and the resulting precipitate was filtered, washed with water (30 mL) and dried in vacuo providing N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-4-methanesulfonyl-benzamide as a white solid, (0.44 g, 71% yield); mp 260-262° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 50/50 CH3CN/0.1% H3PO4, 4.08 (98.31%); 1H NMR (DMSO-d6) δ 1.96-2.03 (m, 1H), 2.31-2.46 (m, 1H), 2.57-2.63 (m, 1H), 2.86-2.98 (m, 1H), 3.27 (s, 3H), 4.31 (d, 1H, J=17.4 Hz), 4.45 (d, 1H, J=17.4 Hz), 4.63 (d, 2H, J=5.7 Hz), 5.11 (dd, 1H, J=13.2 Hz, J=4.8 Hz), 7.48 (d, 1H, J=8.1 Hz), 7.56 (s, 1H), 7.71 (d, 1H, J=7.8 Hz), 8.05 (d, 2H, J=8.4 Hz), 8.14 (d, 2H, J=8.4 Hz), 9.42 (t, 1H, J=6.0 Hz), 10.99 (s, 1H). 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.9, 43.3, 47.1, 51.6, 122.1, 123.0, 127.1, 128.3, 130.4, 138.6, 142.4, 143.0, 143.5, 165.0, 167.9, 171.0, 172.8; LCMS: MH=456; Anal. Calcd for C22H21N3O6S: C, 58.01; H, 4.65; N, 9.23. Found: C, 58.15; H, 4.52; N, 9.04.
