Reaction Steps
A solution of 7-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-propyl]-2,3-dihydro-isoindol-1-one (1.0 g, 2.9 mmol) and cyclopropanecarbonyl chloride (0.32 mL, 3.5 mmol) in THF (10 mL) was heated to reflux for 40 min. The solvent was removed in vacuo. The residue was extracted with ethyl acetate (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 chromatography (Silica Gel) to cyclopropanecarboxylic acid {2-[1-(3-ethoxy-4-methoxy-phenyl)-propyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as a white solid (900 mg, 76% yield): mp, 107-109° C.; 1H NMR (CDCl3) δ 0.84-0.92 (m, 2H, CH2), 0.99 (t, J=7 Hz, 3H, CH3), 1.02-1.13 (, 2H, CH2), 1.44 (t, J=7 Hz, 3H, CH3), 1.64-1.73 (m, 1H, CH), 2.00-2.16 (m, 2H, CH2), 3.86 (s, 3H, CH3), 4.00 (d, J=17 Hz, 1H, CHH), 4.09 (q, J=7 Hz, 2H, CH2), 4.27 (d, J=17 Hz, 1H, NCHH), 5.33 (dd, J=7, 9 Hz, 1H, NCH), 6.83-6.95 (m, 3H, Ar), 7.00 (d, J=8 Hz, 1H, Ar), 7.42 (t, J=8 Hz, 1H, Ar), 8.42 (d, J=8 Hz, 1H, Ar), 10.67 (s, 1H, NH); 13C NMR (CDCl3) δ 8.19, 11.18, 14.78, 16.18, 24.54, 45.64, 55.53, 55.97, 64.58, 111.46, 112.91, 116.68, 117.67, 119.51, 131.96, 132.94, 138.02, 141.37, 148.54, 149.04, 169.55, 172.70; Anal Calcd for C24H28N2O4: C, 70.57; H, 6.91; N, 6.86. Found: C, 70.54; H, 6.91; N, 6.86.
