Preparation method for crystal form II of sorafenib tosylate
A technology of fennel crystal form and toluenesulfonic acid, which is applied in the field of medicinal chemistry, can solve the problems of inconvenient operation, crystal form purity of only 96%, and high drying temperature
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Embodiment 1
[0025] Embodiment 1: WO2006034797 patent method reproduction
[0026] Add 5.00 g of Sorafenib free base to 150 ml of ethanol, add dropwise a solvent of 3.10 g of p-toluenesulfonic acid monohydrate dissolved in 9 ml of ethanol at room temperature, stir and crystallize at room temperature for 1 hour, filter with suction, and filter the cake with ethanol Wash three times, 5ml each time. Drying under reduced pressure at 50°C yielded 5.11 g of sorafenib tosylate crystal form I with a purity of 100%. No other crystalline forms were detected.
Embodiment 2
[0027] Example 2: Effect of Temperature on Sorafenib Mesylate Form II
[0028] The experiment was divided into three groups. In each group, 5.00 g of sorafenib free base was added to 100 ml of ethanol, the temperature was raised to 60°C, 0.60 g of p-methanesulfonic acid monohydrate was added, and stirred until it was dissolved. Afterwards, the temperature of the three groups was lowered to 10°C, -15°C, and -30°C, respectively, and 5ml of ethanol was added dropwise to dissolve 2.50g of p-toluenesulfonic acid monohydrate. After the dropping, stirred and crystallized at 0°C for 6 hours. All three groups were filtered, and the filter cake was washed with ethanol and left for 1 hour. After testing, the obtained crystal forms were all type II. After drying under reduced pressure at 40°C for 8 hours, the three groups obtained 4.86g, 4.63g, and 4.53g of stable crystal form II, respectively.
Embodiment 3
[0029] Example 3: Preparation of Sorafenib Tosylate Form II
[0030] Add 3.00 g of sorafenib free base to 60 ml of ethanol, raise the temperature to 80° C., add 0.36 g of p-toluenesulfonic acid monohydrate, stir until clear, and obtain a solution. Another 1.50 g of p-toluenesulfonic acid monohydrate was added into 3 ml of ethanol to obtain p-toluenesulfonic acid monohydrate ethanol solution. Cool the solution to -30°C, add p-toluenesulfonic acid monohydrate ethanol solution, continue to stir, control the temperature, stir and crystallize to obtain 2.75 g of sorafenib tosylate crystal form II with a purity of 100%.
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