Preparation method of glasdegib intermediate
An intermediate, the technology of Grajib, which is applied in the field of preparation of Grajib intermediates, can solve the problems of difficult acquisition and complicated raw materials, and achieve the goals of reducing production costs, cheap and easy starting raw materials, good industrialization potential and commercial value Effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0057] The present embodiment provides a kind of preparation method of Grajib intermediate, comprises the steps:
[0058] S1: Add 55.5 g (500 mmol) of compound 2 to a 1000 ml single-necked flask with a magnetic stirrer, then add 500 ml of toluene to dissolve compound 2, and then add 10 mmol of p-toluenesulfonic acid Pyridinium salt, and 60.6 g (500 mmol) (S)-tert-butylsulfinamide, connect the water separator, and carry out reflux water separation at 110°C; after 18 hours of reflux water separation reaction, the reaction is complete, remove the water separation After the reaction solution was cooled to room temperature, the toluene solvent was removed by concentrating under reduced pressure (toluene can be recovered and re-distilled, dried and reused); the remaining crude product solid was dissolved with 500 milliliters of dichloromethane, and the organic phase was washed twice with water; The organic phase was dried over anhydrous sodium sulfate, and the solvent was removed un...
Embodiment 2
[0078] The present embodiment provides a kind of preparation method of Grajib intermediate, comprises the steps:
[0079] S1: Add 28 g (250 mmol) of compound 2 into a 1000 ml single-necked flask with a magnetic stirrer, then add 500 ml of toluene to dissolve compound 2, and then add 10 mmol of p-toluenesulfonic acid Pyridinium salt, and 60.6 g (500 mmol) (S)-tert-butylsulfinamide, connect the water separator, and carry out reflux water separation at 120 °C; after 20 hours of reflux water separation reaction, the reaction is complete, remove the water separation After the reaction solution was cooled to room temperature, the toluene solvent was removed by concentrating under reduced pressure (toluene can be recovered and re-distilled, dried and reused); the remaining crude product solid was dissolved with 500 milliliters of dichloromethane, and the organic phase was washed twice with water; The organic phase was dried over anhydrous sodium sulfate, and the solvent was removed u...
Embodiment 3
[0090] The present embodiment provides a kind of preparation method of Grajib intermediate, comprises the steps:
[0091] S1: Add 83.3 g (750 mmol) of compound 2 to a 1000 ml single-necked flask with a magnetic stirrer, then add 500 ml of toluene to dissolve compound 2, and then add 10 mmol of p-toluenesulfonic acid Pyridinium salt, and 60.6 g (500 mmol) (S)-tert-butylsulfinamide, connect the water separator, and carry out reflux and water separation at 130 ° C; after 15 hours of reflux and water separation reaction, the reaction is complete, and the water separation is removed After the reaction solution was cooled to room temperature, the toluene solvent was removed by concentrating under reduced pressure (toluene can be recovered and re-distilled, dried and reused); the remaining crude product solid was dissolved with 500 milliliters of dichloromethane, and the organic phase was washed twice with water; The organic phase was dried over anhydrous sodium sulfate, and the solv...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More