Reaction Steps
N-Methylmorpholine (0.15 g, 1.5 mmol) was added to a stirred suspension of [2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylamino]acetic acid (0.50 g, 1.5 mmol) in 50 mL THF under nitrogen at room temperature. Ethyl chloroformate (0.16 g, 1.5 mmol) was then added. Following 30 minutes stirring at room temperature, cyclopropylamine (0.086 g, 1.5 mmol) was added, and stirring proceeded for 21 hours. The solvent was evaporated in vacuo, and the dark yellow residue was dissolved in ethyl acetate (200 mL) and washed with sat. sodium bicarbonate (2×100 mL), water (100 mL), 1N citric acid (2×100 mL), water (100 mL) and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to provide 0.15 g (27%) of the product as a yellow solid: mp 240-242° C.; 1H NMR (DMSO-d6) δ 0.39-0.45 (m, 2H), 0.59-0.73 (m, 2H), 2.02-2.06 (m, 1H), 2.45-2.70 (m, 3H), 2.96-2.83 (m, 1H), 3.88 (d, J=5.3 Hz, 2H), 5.07 (dd, J=12.5 Hz, J=5.3 Hz, 1H), 6.83-6.92 (m, 2H), 7.07 (d, J=7.0 Hz, 1H), 7.60 (t, J=7.9 Hz, 1H), 11.11 (s, 1H); 13C NMR (DMSO-d6) δ 5.57, 22.13, 22.26, 30.96, 44.92, 48.59, 109.77, 110.88, 117.42, 132.02, 136.17, 145.80, 167.28, 168.68, 169.46, 170.07, 172.77; Anal. calcd. for C18H18N4O5: C, 58.37; H, 4.90; N, 15.13. Found: C, 58.16; H, 4.64; N, 14.84.
