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A kind of purification method of abiraterone acetate

A technology of abiraterone acetate and a purification method, which is applied in the field of purification of raw material drug abiraterone acetate, can solve the problems of high production cost, difficult filtration, sticky filter cake, etc., achieve low cost, simple operation, and simplified purification process Effect

Active Publication Date: 2016-04-13
LUNAN PHARMA GROUP CORPORATION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] However, there are certain disadvantages in the purification method of this process: when methanesulfonic acid and abiraterone acetate form a salt, a thick suspension is formed, which is difficult to filter, and the filtered cake is viscous, and it is easy to leave wrapped impurities
The purity of abiraterone acetate mesylate obtained by filtration is relatively low, and it must be neutralized with alkali to obtain abiraterone acetate after recrystallization and purification, which increases the time and difficulty of operation, and is also unfavorable for large-scale industrial production
[0010] CN201010597372.9 improves the above-mentioned purification method, forms a salt with trifluoromethanesulfonic acid and abiraterone acetate, and then precipitates from a suitable solvent, and the obtained abiraterone acetate trifluoromethanesulfonate is dry and easy to filter, and the purity reaches More than 97%, but, because trifluoromethanesulfonic acid is expensive, make the production cost of technology higher, now urgently need to find a kind of acid, both will be cheap, can form dry and easy filterable salt with abiraterone acetate again urgently, and The purity is high, no need for recrystallization and purification, neutralized with alkali, and the target product Abiraterone acetate can be obtained

Method used

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  • A kind of purification method of abiraterone acetate
  • A kind of purification method of abiraterone acetate
  • A kind of purification method of abiraterone acetate

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Embodiment 1

[0024] The preparation of embodiment 1 Abiraterone acetate crude product

[0025] Add 300g (0.91mol) of dehydroepiandrosterone acetate into 2.5L of dichloromethane, stir to dissolve and cool down to 0-10°C, slowly add 183mL (1.08mol) of trifluoromethanesulfonic anhydride dropwise, and stir after the addition is complete After 10 min, 158.6 mL (0.91 mol) of diisopropylethylamine (DIEA) was added dropwise. Insulate and stir for 4 hours, add 2 L and stir thoroughly, separate the layers, extract the aqueous layer with 200 mL of dichloromethane, combine the organic layers and wash with 600 mL×2 water, concentrate to dryness under reduced pressure, add 2.5 L of tetrahydrofuran to dissolve and set aside.

[0026] Add 4.5g (6.4mmol) bistriphenylphosphine palladium dichloride, 120g (0.82mol) diethyl (3-pyridyl) borane, 356g (3.36mol) sodium carbonate and 1600mL water successively to the above tetrahydrofuran solution , stirred and refluxed for 2 hours. Then add 1.5 L of water and 1.8...

Embodiment 2

[0027] The purification of embodiment 2 Abiraterone acetate crude product (phosphoric acid is a salt-forming reagent)

[0028] Add 496.5g of abiraterone acetate crude oil to 2.5L tetrahydrofuran, stir to dissolve, slowly add dropwise 90mL (1.55mol) of phosphoric acid, after the dropwise addition, stir for 10min, stand at room temperature for crystallization for 12h, suction filter, use for filter cake A small amount of tetrahydrofuran was washed and dried to obtain 226.3 g of light yellow crystals, namely abiraterone acetate phosphate, with a yield of 50.9%. HPLC showed that the purity was 98.24%, and there were no impurities greater than 1%.

Embodiment 3

[0029] The preparation of embodiment 3 Abiraterone acetate (with Abiraterone acetate phosphate as raw material)

[0030] Add 226.3g (0.46mol) of abiraterone acetate phosphate into 2.5L of dichloromethane, stir evenly, then add 285g (3.4mol) of sodium bicarbonate and 2L of water, after stirring for 2 hours, let it stand for liquid separation, and water the organic phase Wash, dry over anhydrous magnesium sulfate, decolorize with activated carbon, filter, and concentrate to obtain 146.2 g of a white solid, which is abiraterone acetate, with a yield of 79.2%. HPLC shows that the purity is 98.71%, and there are no impurities greater than 1%.

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Abstract

The present invention provides a purifying method for abiraterone acetate. According to the method, phosphoric acid is adopted as a salt forming reagent to react with a abiraterone acetate crude product to obtain a light yellow crystal, wherein the light yellow crystal is the abiraterone acetate phosphate, is easily filtered, and has the purity more than 98%, the abiraterone acetate phosphate can be used for the next reaction without further purification to prepare the abiraterone acetate, and the purity of the abiraterone acetate prepared by freeing can be more than 98%; the purification process is simplified, the production cost is reduced, and the method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, and further relates to a method for purifying a raw drug abiraterone acetate. Background technique [0002] Abiraterone acetate was invented by researchers at the Royal Marsden Hospital (a world-renowned cancer research and treatment center) in southwest London. The drug is a cytochrome oxidase CYP450c17 inhibitor, which reduces androgen levels by inhibiting the key enzyme in androgen synthesis-CYP450c17, and has inhibitory effects on androgen in the testis and other parts of the body. At present, it has been proved that abiraterone acetate can inhibit androgen in prostate cancer patients. A phase II trial shows that the drug can not only reduce the prostate specific antigen by more than 50%, but also shrink the tumors of 41% of patients. Another phase III clinical trial results show that this product can significantly prolong the life of patients with advanced prostate cancer, including patie...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J43/00
Inventor 王红波赵荐飞张俭
Owner LUNAN PHARMA GROUP CORPORATION
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