Compounds adopted as cMet inhibitor, preparation method and uses thereof
A compound and solvate technology, which is applied in the preparation of hydroxyl compounds, organic compounds, carboxylic acids by oxidation, etc., can solve the problems of patient intolerance and high toxicity
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0328] Example 1: 3-[(2,6-dichloro-3-fluorophenyl)sulfinyl]-5-(1-(piperidin-4-yl)-1H-(pyrazol-4-yl) -1H-Pyrrolo[2,3-b]pyridine
[0329]
[0330] Step 1: Synthesis of 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine
[0331] Add 5-bromo-1H-pyrrolo[2,3-b]pyridine (2.0g, 10.2mmol) into 20mL acetone, stir to dissolve, then add N-iodosuccinimide (2.7g, 12.0mmol ), stirred at room temperature for 1 h. After the reaction was completed, the solvent was evaporated under reduced pressure, dissolved in ethyl acetate (20mL), then washed successively with saturated sodium thiosulfate solution (2×30mL) and saturated brine (2×30mL), and the organic phase was washed with anhydrous sodium sulfate Dry and concentrate to obtain off-white solid (2.9g, 88.0%). 1HNMR(400MHz, CDCl3)δ9.27(s,1H),8.37(d,J=2.0Hz,1H),7.93(d,J=1.6Hz,1H),7.45(d,J=2.5Hz,1H) .
[0332] Step 2: Synthesis of 5-bromo-3-iodo-1-(4-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine
[0333] Add 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (2...
Embodiment 2
[0342] Example 2: 3-(2,6-dichloro-3-fluorophenylsulfoxide)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H- Synthesis of Pyrazolo[3,4-b]pyridine
[0343]
[0344] Step 1: Synthesis of 5-bromo-3-iodo-1H-pyrazolo[3,4-b]pyridine
[0345] Add 5-bromo-1H-pyrazolo[3,4-b]pyridine (2.0g, 10.1mmol) into 20mL N,N-dimethylformamide, stir to dissolve, then add flake potassium hydroxide (1.2 g, 21.4mmol), stirred and reacted at room temperature for 10 minutes, then added solid iodine (2.8g, 11.1mmol), stirred and reacted for 4 small experiments at room temperature, then diluted with water (30mL), extracted with ethyl acetate (3×20mL), Then it was washed successively with saturated sodium thiosulfate solution (2×30 mL) and saturated brine (2×30 mL), and the organic phase was dried over anhydrous sodium sulfate and concentrated. Then the solid was dissolved with dioxane (30 mL), potassium hydroxide (1.2 g, 21.4 mmol) was added, and the reaction was stirred at room temperature for 10 minutes...
Embodiment 3
[0356] Example 3: 3-(1-(2,6-dichloro-3-fluorophenyl)cyclopropyl)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl Synthesis of )-1H-pyrazolo[3,4-b]pyridine
[0357]
[0358] Step 1: Synthesis of 2,6-dichloro-3-fluoro-phenylethanol
[0359]Add 2,4-dichlorofluorobenzene (165.0g, 1000.0mmol) into 500mL of anhydrous tetrahydrofuran, then cool down to -78°C, add n-butyl lithium (42.0mL, 2.5M, 1050.0mmol) dropwise, and -78°C The reaction was stirred for 1 hour, then ethylene oxide (44.0 g, 1000.0 mmol) was added, and the reaction was stirred for another 2 hours at -78°C. After the reaction was completed, it was quenched with saturated ammonium chloride solution, extracted with ethyl acetate (3×200mL), the organic phase was washed with water (2×100mL) and saturated brine (2×100mL), dried over anhydrous sodium sulfate, and concentrated A colorless liquid (156.7g, 75.0%) was obtained. 1HNMR (400MHz, CDCl3) δ7.25(m,1H),7.03(m,1H),3.89(m,2H),3.29(m,2H).
[0360] Step 2: Synthesis of 2,6-di...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More