Reaction Steps
5-(t-Butyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]isoindoline-1,3-dione was prepared as described for Example 8 from 3-[5-(tert-butyl)-1,3-dioxoisoindolin-2-yl]-3-(3-ethoxy-4-methoxyphenyl)propanoic acid (2.0 g, 4.7 mmol), carbonyldiimidazole (0.81 g, 5.0 mmol), formic hydrazide (0.35 g, 5.8 mmol), and phosphorus oxychloride (1.0 mL, 10.7 mmol) in acetonitrile (20 mL). The product was isolated as a white solid (800 mg, 38% yield): mp, 136.0-138.5° C.; 1H NMR (CDCl3) δ 1.35 (s, 9H, CH3), 1.44 (t, J=6.9 Hz, 3H, CH3), 3.79 (dd, J=5.9, 16.1 Hz, 1H, CHH), 3.84 (s, 3H, CH3), 4.11 (q, J=7.1 Hz, 2H, CH2), 4.38 (dd, J=10.3, 15.8 Hz, 1H, CHH), 5.80 (dd, J=5.9, 10.4 Hz, 1H, NCH), 6.82 (d, J=8.2 Hz, 1H, Ar), 7.11-7.17(m, 2H, Ar), 7.70 (br s, 2H, Ar), 7.82 (br s, 1H, Ar), 8.29 (s, 1H, Ar); 13C NMR (CDC3) δ 14.71, 27.73, 31.08, 35.72, 51.78, 55.92, 64.44, 111.36, 112.58, 120.31, 120.63, 123.26, 128.94, 130.33, 131.14, 131.84, 148.41, 149.42, 153.02, 158.82, 164.07, 168.25, 168.39; Anal Calcd for C25H27N3O5+0.11 H2O: C, 66.51; H, 6.08; N, 9.31; H2O, 0.43. Found: C, 66.42; H, 5.83; N, 9,18; H2O, 0.43.
