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Preparation method of abiraterone acetate

A technology of abiraterone acetate and abiraterone, which is applied in the directions of steroids, chemical recovery, organic chemistry, etc., can solve the problems of cumbersome operation, inability to realize large-scale production, etc., achieves optimized reaction operating conditions, and is suitable for industrial scale-up The effect of production and reaction cost saving

Inactive Publication Date: 2016-04-20
JIANGSU LIANHUAN PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0027] The first object of the present invention is to provide a preparation method of abiraterone acetate. In the method of the present invention, there is no need for cumbersome chromatographic purification or additional addition of inorganic salts to precipitate crystals, thus solving the problem of complex operations in the prior art and the inability to Technical Issues Achieving Mass Production

Method used

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  • Preparation method of abiraterone acetate
  • Preparation method of abiraterone acetate
  • Preparation method of abiraterone acetate

Examples

Experimental program
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Effect test

Embodiment 1

[0087]1. Preparation of crude abiraterone: In a 100L reaction kettle, add KOH (3.36kg, 60.0mol) and 32kg water to stir to dissolve, then add THF32L, 17-iodo-androster-5,16-diene-3β in sequence -Alcohol acetate (7.96kg, 20.0mol), bis(triphenylphosphine) palladium chloride [Pd(PPh 3 ) 2 Cl 2 ] (140g, 0.2mol), diethyl (3-pyridyl) borane (2.94kg, 20.0mol) was heated to reflux, and the reaction was stirred for 24 hours. The reaction solution was concentrated under reduced pressure to remove THF, and a large amount of solid was precipitated. Add 80L of water to the reaction kettle again, and continue to stir for 20 minutes. A large amount of light gray solid was obtained by centrifugation. The solid was rinsed with a large amount of water to pH 7-8, and the obtained solid was dried at 50-60° C. to obtain 7.23 kg of crude abiraterone.

[0088] 2. Preparation of Abiraterone Acetate:

[0089] 2.1 Purification of Abiraterone

[0090] Add the crude abiraterone obtained in step 1 in...

Embodiment 2

[0098] Add 50 g of the crude abiraterone acetate product prepared in step 2.2 of Example 1 into 500 ml of ethanol, heat and stir, and after it is completely dissolved, add 2.5 g of activated carbon, reflux for 0.5 h, and filter while it is hot. Add 500ml of purified water to the obtained filtrate, stir to precipitate crystals for 2 hours, and after the system reaches room temperature, cool to 0-5°C, and continue to stir to precipitate crystals for 12 hours. The white solid obtained by filtration was dried at 50-60° C., and dried to a constant weight to obtain 37.3 g of white crystals, with a mass yield of 74.5%.

[0099] The HPLC test purity is 99.79%, the largest single impurity is 0.058%, the specific test chart is shown in the attached picture image 3 .

Embodiment 3

[0101] Add 50 g of the crude abiraterone acetate product prepared in step 2.2 of Example 1 into 400 ml of methanol, heat and stir, and after it is completely dissolved, add 2.5 g of activated carbon to reflux for 0.5 h, and filter while it is hot. Add 400ml of purified water to the obtained filtrate, stir to precipitate crystals for 2 hours, and after the system reaches room temperature, cool to 0-5°C, and continue to stir to precipitate crystals for 12 hours. The white solid was filtered and dried at 50-60° C., and dried to a constant weight to obtain 31.6 g of white crystals, with a mass yield of 63.2%.

[0102] The HPLC test purity is 99.89%, the largest single impurity is 0.03%, and the specific test chart is shown in the attached picture Figure 4 .

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Abstract

The invention provides a preparation method of abiraterone acetate. According to the method, firstly an intermediate product, namely coarse abiraterone is purified and refined, then a purified product of abiraterone is acetylated, the abiraterone acetate is directly prepared, accordingly the coarse abiraterone product which is in an off-white color, relatively high in purity and less in impurity is obtained directly, the coarse abiraterone product is further simply crystallized, the abiraterone acetate which is high in purity and meets the medicinal requirement can be obtained, and therefore the step of chromatography or tedious purification of an inorganic salt-precipitated crystal in a traditional method can be avoided. The method has the advantages of being more convenient and faster in operation and purification treatment step, more suitable for industrialized amplification production and the like.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of abiraterone acetate. Background technique [0002] Abiraterone acetate is a kind of androgen synthesis inhibitor, which can inhibit the generation of the enzyme complex of CYP17, thereby reducing the production of androgen in the body, and then can be used as a drug for treating advanced prostate cancer. Its structure is shown in formula 1 below: [0003] [0004] On April 28, 2011, the U.S. Food and Drug Administration (FDA) approved the application of abiraterone acetate (trade name: Zytiga) as a drug for the treatment of advanced prostate cancer. After it is used in combination with prednisone, it can be used For the treatment of metastatic prostate cancer patients who have received paclitaxel chemotherapy regimens but have not responded. At the same time, the combination of Zytiga and prednisone showed a 35% reduction in patient mortality compared wit...

Claims

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Application Information

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IPC IPC(8): C07J43/00
CPCY02P20/582C07J43/003
Inventor 扈田进田宗勇何秋范庆玉俞波秦雄剑
Owner JIANGSU LIANHUAN PHARMA
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