Reaction Steps
A mixture of (1S)-7-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-2,3-dihydro-isoindol-1-one (0.5 g, 1.2 mmol) and dimethylcarbamyl chloride (0.6 mL, 6.5 mmol) was heated to reflux for 2 hours. The solvent was removed in vacuo. The residue was extracted with methylene chloride (50 mL) and sodium hydrogen carbonate (sat, 50 mL). The organic layer was washed with brine (50 mL) and dried over MgSO4. The solvent was removed in vacuo, and the residue was purified with prep HPLC to give (1S)-3-(2-[1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-3-oxo-2,3,dihydro-1H-isoindol-4-yl}-1,1-dimethyl-urea as a white solid (280 mg, 48% yield): mp 170-172° C.; 1H NMR (CDCl3) δ 1.44 (t, J=7 Hz, 3H, CH3), 2.91 (s, 3H, CH3), 3.11 (s, 6H, 2 CH3), 3.70 (dd, J=5, 15Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.08 (q, J=7 Hz, 2H, CH2), 4.16-4.25 (m, 2H, CHH, NCHH), 4.41 (d, J=17Hz, 1H, NCHH), 5.69 (dd, J=5, 10 Hz, 1H, NCH), 6.83-6.95 (m, 4H, Ar), 7.43 (t, J=8 Hz, 1H, Ar), 8.33 (d, J=8Hz, 1H, Ar), 9.85 (s, 1H, NH); 13C NMR(CDCl3) δ 14.71, 3.32, 41.50, 48.06, 51.89, 55.99, 56.16, 64.65, 131.62, 112.30, 115.09, 116.63, 116.77, 119.34, 129.51, 133.68, 139.67, 141.19, 148.93, 149.80, 155.31, 170.64. Analy. Calculated for C23H29N3O6S+1 H2O: C 55.97; H 6.33; N 8.51; H2O 3.65. Found: C 55.57; H 6.02; N 8.44; H2O, 2.97.
