Indolinone compounds and uses thereof
A technology of compounds and solvates, applied in the field of indolinone compounds and their uses, can solve problems such as toxicity and poor patient condition
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[0130] Preparation of Compounds of Formula (I)
[0131]
[0132] Compounds of formula (I) are prepared according to the synthetic schemes set forth herein. In methanol (5 mL), in the presence of diethylamine (10 drops), the ketone of formula (II) (4.0 equivalents) was condensed with the isatin derivative of formula (III) (1.0 equivalents), and the mixture was incubated at room temperature Stir for 24 hours. The reaction mixture was concentrated and purified by flash chromatography using dichloromethane / methanol as eluent to give pure product. Further purification was performed by recrystallization from methanol. The substituents on the ketones and on the isatin derivatives are chosen to give compounds of formula (I) labeled as Example 1 to Example 23 below. To the compound of embodiment 1 to embodiment 26 thus obtained, use Varian-400 spectrometer (400MHz) to record 1 H NMR spectrum. Chemical shifts are given in ppm downfield with tetramethylsilane as an internal sta...
Embodiment 2
[0150]
[0151] To a solution of 4,7-dichloroindole-2,3-dione (A) (300 mg, 1.39 mmol) in 15 mL of methanol was added 1-(4-((aziridine-1-yl)phenyl) Ethanone (B) (0.9g, 5.5mmol) and 10 drops of diethylamine (2). The reactant was stirred at 50°C for 24 hours. The solvent was removed, and the residue was subjected to flash chromatography (0-5% methanol / CH 2 Cl 2 ) to obtain off-white solid. 3-(2-(4-(aziridine-1-yl)phenyl)-2-oxoethyl)-4,7-dichloro-3-oxindol-2-one (Example 2 ): off-white solid; 1 H NMR (DMSO-d6, 400MHz) δ2.16(s, 4H), 3.64(d, 1H, J=16Hz), 4.32(d, 1H, J=16Hz), 6.41(s, 1H), 6.89(d , 1H, J=8Hz), 7.05(d, 2H, J=8Hz), 7.30(d, 1H, J=8Hz), 7.80(d, 2H, J=8Hz), 10.95(s, 1H).
[0152] 4,7-dichloro-3-hydroxy-3-(2-(4-isopropylphenyl)-2-oxoethyl)indol-2-one (Example 3): off-white solid; 1 H NMR (DMSO-d6, 400MHz) δ1.21(d, 6H, J=4Hz), 2.95(m, 1H), 3.69(d, 1H, J=16Hz), 4.39(d, 1H, J=16Hz) , 6.45(s, 1H), 6.90(d, 1H, J=8Hz), 7.29(d, 1H, J=8Hz), 7.38(d, 2H, J=8Hz), 7.85(d, 2H...
Embodiment 7
[0155]
[0156] 1-(4-Cyclopropylphenyl)ethanone (B) (0.9 g , 5.5mmol) and 10 drops of diethylamine (2). The reaction was stirred at 50°C for 24 hours. The solvent was removed and the residue was subjected to flash chromatography (0-5% methanol / CH 2 Cl 2 ) to obtain off-white solid. 4,7-dichloro-3-(2-(4-cyclopropylphenyl)-2-oxoethyl)-3-oxindol-2-one (Example 7): off-white solid; 1 H NMR (DMSO-d6, 400MHz) δ0.76(m, 2H), 1.06(m, 2H), 2.0(m, 1H), 3.65(d, 1H, J=16Hz), 4.35(d, 1H, J =16Hz), 6.43(s, 1H), 6.89(d, 1H, J=8Hz), 7.19(d, 2H, J=8Hz), 7.30(d, 1H, J=8Hz), 7.79(d, 2H, J=8Hz), 10.97(s, 1H).
[0157] 3-(2-(4-(1H-pyrazol-1-yl)phenyl)-2-oxoethyl)-4,7-dichloro-3-oxindol-2-one (Example 8 ): off-white solid; 1 H NMR (DMSO-d6, 400MHz) δ3.72(d, 1H, J=16Hz), 4.41(d, 1H, J=16Hz), 6.47(s, 1H), 6.62(d, 1H, J=4Hz) , 6.90(d, 1H, J=8Hz), 7.31(d, 1H, J=8Hz), 7.84(d, 1H, J=4H), 7.99(d, 2H, J=8Hz), 8.06(d, 2H , J=8Hz), 8.66(d, 1H, J=4Hz), 10.98(s, 1H).
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