Reaction Steps
2-[1-(3-Ethoxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]benzo[e]isoindoline-1,3-dione was prepared by the procedure used in Example 1. Thus, reaction of 3-(1,3-dioxobenzo[e]isoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propanoic acid (1.50 g, 3.58 mmol), carbonyidiimidazole (0.70 g, 4.3 mmol) and formic hydrazide (310 mg, 5.16 mmol) in tetrahydrofuran (20 mL) gave crude 3-(1,3-dioxobenzo[e]isoindolin-2-yl)-N-carbonylamino-3-(3-ethoxy4-methoxyphenyl)propanamide (1.0 g, 2.2 mmol), which was then treated with phosphorus oxychloride (POCl3, 0.4 mL, 4.3 mmol) in acetonitrile (10 mL). The product was obtained as a yellow solid (135 mg, 8% overall yield): mp, 139.0-141.5° C.; 1H NMR (CDCl3) δ 1.47 (t, J=7.2 Hz, 3H, CH3), 3.85 (s, 3H, CH3), 3.87 (dd, J=6.0, 15.6 Hz, 1H, CHH), 4.13 (q, J=6.9 Hz, 2H, CH2), 4.42 (dd, J=10.2, 15.6 Hz, 1H, CHH), 5.87 (t, J=5.9, 10.4 Hz, 1H, NCH), 6.84 (d, J=8.7 Hz, 1H, Ar), 7.18-7.27 (m, 2H, Ar), 7.64-7.75 (m, 2H, Ar), 7.81 (d, J=8.3 Hz, 1H, Ar), 7.94 (d, J=7.6 Hz, 1H, Ar), 8.14 (d, J=8.2 Hz, 1H, Ar), 8.29 (s, 1H, CH), 8.90 (d, J=7.5 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.63, 27.79, 51.69, 55.84, 64.39, 111.34, 112.53, 118.41, 121.22, 124.83, 126.88, 127.93, 128.62, 128.74, 129.44, 130.31, 130.87, 135.06, 136.59, 148.37, 149.36, 152.95, 164.04,168.51, 169.07; Anal Calcd for C25H21N3O5: C, 67.71; H, 4.77; N, 9.48. Found: C, 67.80; H, 4.95; N, 9.20.
