Reaction Steps
A solution of 4-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindoline-1,3-dione (500 mg, 1.20 mmol) and 2-bromopropionyl bromide (0.140 mL, 1.34 mmol) in methylene chloride (10 mL) was stirred at room temperature overnight. An additional 0.1 mL of 2-bromopropionyl bromide (1 mol) was added and the mixture stirred overnight. To the mixture was added brine (4 mL), Sodium bicarbonate (sat, 10 mL) and methylene chloride (15 mL). The organic layer was separated, was washed with brine (10 mL), and dried over magnesium sulfate. The solvent was removed in vacuo to give a yellow oil. The oil was slurried in ether (10 mL). The resulting suspension was filtered and the solid washed with ether to give 2-bromo-N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}propanamide as a white solid (500 mg, 76% yield): 1H NMR (CDCl3) δ 1.46 (t, J=6.9 Hz, 3H, CH3), 1.97 (d, J=6.9 Hz, 3H, CH3), 2.86 (s, 3H, CH3), 3.75 (dd, J=4.5, 14.4 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.49-4.59 (m, 2H, CHH, CH), 4.09 (q, J=6.9 Hz, 2H, CH2), 5.87 (dd, J=4.4, 10.3 Hz, 1H, NCH), 6.82-6.85 (m, 1H, Ar), 7.09-7.13 (m, 2H, Ar), 7.53 (d, J=7.3 Hz, 1H, Ar), 7.68 (t, J=7.5 Hz, 1H, Ar), 8.73 (d, J=8.4 Hz, 1H, Ar), 10.19 (s, 1H, NH); 13C NMR (CDCl3) δ 14.61, 22.42, 41.54, 43.78, 48.67, 54.44, 55.87, 64.45, 111.39, 112.3, 116.10, 116.79, 120.35, 124.76, 129.14, 131.13, 136.02, 136.82, 148.55, 149.70, 167.28, 168.42, 169.11.
