Kinase inhibitors
a kinase inhibitor and inhibitor technology, applied in the field of kinase inhibitors, can solve problems such as malignant tumor growth, uncontrolled cell proliferation, or defects in key developmental processes
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example 426
5-Fluoro-3-{5-[2-(4-hydroxy-piperidin-1-yl)-ethyl]-3,3-dimethyl-3H-isobenzofuran-1-ylidene}-1,3-dihydro-indol-2-one
To a stirred solution of 5-fluorooxindole (7.86 g, 52 mmol) in anhydrous THF (60 ml) under nitrogen was added 1.0M LiHMDS / THF solution (104 ml, 104 mmol). The mixture was stirred at room temperature for 15 minutes, and then 5-[2-(4-hydroxy-piperidin-1-yl)-ethyl]-3,3-dimethyl-3H-isobenzofuran-1-one (5.0 g, 17.3 mmol) was added. After stirring at room temperature for 2 hours, the mixture was quenched with 50 ml of 2.5M H2SO4, heated at 65° C. for 30 minutes and poured into 500 ml of water. The mixture was basified with 5M NaOH to about pH=9 and continuously stirred at room temperature for 16 hours. The resulting solids were filtered, rinsed with water, dried under vacuum to give the title compound as a yellow solid (4.74 g, 65%).
1H NMR (500 MHz, DMSO-d6) δ ppm 1.34-1.43 (m, 2H) 1.69-1.76 (m, 8H) 2.10 (br. s., 2H) 2.57 (t, J=7.32 Hz, 2H) 2.76-2.83 (m, 2H) 2.87 (t, J=7.32 H...
example 474
3-[5-(3-Diethylamino-propyl)-3,3-dimethyl-3H-isobenzofuran-1-ylidene]-5-fluoro-1,3-dihydro-indol-2-one
A solution of methanesulfonic acid 3-[1-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidene)-3,3-dimethyl-1,3-dihydro-isobenzofuran-5-yl]-propyl ester (170 mg, 0.39 mmol) and diethylamine (0.30 ml, 2.92 mmol) in dioxane (1.6 ml) was heated at 75° C. in a pressure tube for 36 hours. The mixture was evaporated, dissolved in EtOAc, and the EtOAc washed with H2O and brine. The aqueous layer was also extracted with CHCl3. The organic layers were combined, dried over anhydrous Na2SO4, and then evaporated to a yellow film. The sample was passed through a plug of silica gel eluting with 10% methanol in CHCl3 to give a yellow-orange solid. The solid was dissolved in EtOAc, washed with saturated aqueous NaHCO3, brine, dried over anhydrous Na2SO4, and evaporated to a yellow solid. The solid was chromatographed eluting with CHCl3 / MeOH to give the title compound as a yellow solid (88 mg, 54%).
1H NMR (50...
example 481
3-[5-(3-Diethylamino-propyl)-3-methyl-3H-isobenzofuran-1-ylidene]-5-fluoro-1,3-dihydro-indol-2-one
Experimental procedure similar to Example 474.
1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.08 Hz, 6H) 1.73 (d, J=6.83 Hz, 3H) 1.87 (dt, J=14.16, 7.08 Hz, 2H) 2.51 (t, J=7.32 Hz, 2H) 2.54-2.61 (m, 4H) 2.77 (t, J=7.81 Hz, 2H) 5.88 (q, J=6.83 Hz, 1H) 6.76 (dd, J=8.79, 4.39 Hz, 1H) 6.84 (td, J=8.91, 2.69 Hz, 1H) 7.22 (s, 1H) 7.38 (d, J=8.30 Hz, 1H) 7.70 (dd, J=9.52, 2.68 Hz, 1 H) 7.73 (s, 1H) 9.58 (d, J=8.30 Hz, 1H).
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