Reaction Steps
A solution of (3R)-3-(7-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(3-ethoxy-4-methoxy-phenyl)-N,N-dimethyl-propionamide (1.1 g, 2.8 mmol) and dimethylcarbamyl chloride (0.5 mL, 5.4 mmol) in THF (5 mL) was heated to reflux for 2 days. The solvent was removed in vacuo to give a solid, which was purified with prep HPLC to give (3R)-3-[7-(3,3-dimethyl-ureido)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxy-phenyl)-N,N-dimethyl-propionamide as a white solid (450 mg, 34% yield): mp 105-107° C.; 1HNMR (CDCl3) δ 1.44 (t, J=7 Hz, 3H, CH3), 2.90 (s, 3H, CH3), 3.05 (dd, J=6, 16 Hz, 1H, CHH), 3.09 (s, 9H,3CH3), 3.46 (dd, J=9.15 Hz, 1H, CHH), 3.85 (s, 3H, CH3), 4.07 (q, J=7 Hz, 2H, CH2), 4.22 (d, J=17 Hz, 1H, NCHH), 4.41 (d, J=17 Hz, 1H, NCHH), 5.63 (dd, J=6, 9 Hz, 1H, NCH), 6.91-6.96 (m, 4H, Ar), 7.39 (t, J=8 Hz, 1H, Ar), 8.30 (d, J=8 Hz, 1H, Ar), 9.99 (s, 1H, NH); 13CNMR (CDCl3) δ 14.76, 35.57, 36.31, 36.38, 37.45, 48.70, 53.35, 55.97, 64.53, 111.46, 112.63, 115.07, 116.27, 117.57, 119.16, 131.90, 133.02, 139.61, 141.54, 148.55, 149.08, 155.49, 149.69, 170.15. Analy. Calculated for C25H32N4O5+1.2H2O: C, 61.26; H, 7.07; N, 11.43; H2O, 4.41. Found: C, 60.89; H, 6.95; N, 11.10; H2O, 4.04.
