Réaction #2355274

Équation de réaction

3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanoic acid

carbonyidiimidazole

formic hydrazide

→

2-[1-(3-Cyclopentyloxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]-5-methylisoindoline-1,3-dione

N-carbonylamino-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanamide

Rendement 174.5%

Solvants

ethyl acetate

Conditions de réaction

Mode opératoire

2-[1-(3-Cyclopentyloxy-4-methoxyphenyl)-2-(1,3,4-oxadiazol-2-yl)ethyl]-5-methylisoindoline-1,3-dione was prepared by the procedure of Example 1. Reaction of 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanoic acid (2.33 g, 5.5 mmol), carbonyidiimidazole (1.07 g, 6.59 mmol) and formic hydrazide (436 mg, 7.26 mmol) in ethyl acetate (20 mL) gave crude N-carbonylamino-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(5-methyl-1,3-dioxoisoindolin-2-yl)propanamide (2.24 g, 4.8 mmol), which was then treated with phosphorus oxychloride (0.9 mL, 9.6 mmol) in acetonitrile (10 mL). The product was obtained as a white solid (728 mg, 32% overall yield): mp, 184.0-186.5° C.; 1H NMR (CDCl3) δ 1.55-2.00 (m, 8H, C5H8), 2.48 (s, 3H, CH3), 3.81 (s, 3H, CH3), 3.82 (dd, J=6.1, 15.7 Hz, 1H, CHH), 4.36 (dd, J=10.3, 15.7 Hz, 1H, CHH), 4.74-4.81 (m, 1H, OCH), 5.79 (dd, J=5.9, 10.3 Hz, 1H, NCH), 6.80 (d, J=8.4 Hz, 1H, Ar), 7.10 (dd, J=2.0, 8.3 Hz, 1H, Ar), 7.18 (d, J=2.0 Hz, 1H, Ar), 7.47 (d, J=7.5 Hz, 1H, Ar), 7.59 (s, 1H, Ar), 7.67 (d, J=7.6 Hz, 1H, Ar), 8.28 (s, 1H, CH); 13C NMR (CDCl3) δ 21.95, 24.09, 27.75, 32.77, 51.79, 56.00, 80.48, 111.73, 114.51, 120.16, 123.34, 123.95, 129.05, 130.22, 132.03, 134.65, 145.44, 147.75, 150.03, 153.00, 164.08, 167.98, 168.11; Anal Calcd for C25H25N3O5+0.13 Et2O: C, 67.05; H, 5.80; N, 9.19. Found: C, 66.95; H, 5.88; N, 8.97. (HNMR showed the sample contained 0.13 equiv. of ether).

Source