Reaction Steps
To a solution of 4-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]benzonitrile (0.41 g, 1.0 mmol) in dimethylsulfoxide (20 mL) was added hydroxylamine (50% w/w solution in water, 2.0 mL, 33 mmol). The mixture was heated at 80° C. for 16 h, allowed to cool to ambient temperature and diluted with water (50 mL), causing a precipitate to be deposited. The solid was collected by filtration and combined with pyridine (2.0 mL) and acetic anhydride (0.2 g, 2.0 mmol) in a 10 mL microwave reaction vessel. The mixture was heated at 170° C. for 15 min under microwave irradiation, allowed to cool to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexanes to afford 1′-[4-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.52 g, 85%) as a colorless solid: mp 174-175° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 8.06-8.00 (m, 2H), 7.42 (d, J=8.3 Hz, 2H), 7.22-7.13 (m, 2H), 7.04-6.97 (m, 1H), 6.75 (d, J=7.7 Hz, 1H), 6.50 (s, 1H), 6.23 (s, 1H), 5.12 (d, J=15.8 Hz, 1H), 4.94 (d, J=8.9 Hz, 1H), 4.85 (d, J=15.8 Hz, 1H), 4.66 (d, J=8.9 Hz, 1H), 4.21-4.07 (m, 4H), 2.63 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 177.6, 176.6, 168.0, 155.3, 144.7, 141.9, 138.4, 132.2, 128.9, 128.0, 127.8, 126.5, 124.0, 123.6, 120.9, 111.5, 109.2, 99.5, 80.1, 58.1, 43.9, 12.4; MS (ES+) m/z 467.9 (M+1).
