Method for preparing abiraterone acetate without heavy-metal residue

A technology of abiraterone acetate and acid-binding agent, which is applied in the production of steroids, bulk chemicals, organic chemistry, etc., can solve the problems of unsuitability for large-scale production, harsh operation methods, unfavorable material preparation and operation, etc., and achieve good Prospect of industrial application and effect of cost reduction

Active Publication Date: 2013-04-24
SUZHOU LEINA PHARMA RES DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0013] However, the reaction time is long, the energy consumption is high, and the requirements for the reaction vessel are relatively high. At the same time, the raw material diethyl (3-pyridyl) borane is very expensive, and column chromatographic separation is required in the reaction process, which is not suitable for large-scale production.
[0014] Chinese patent CN101044155A discloses abiraterone-3-ester methanesulfonate and its preparation method, but the method is still in the laboratory scale, and the operation method is harsh, which is not conducive to the preparation and operation of industrial production

Method used

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  • Method for preparing abiraterone acetate without heavy-metal residue
  • Method for preparing abiraterone acetate without heavy-metal residue
  • Method for preparing abiraterone acetate without heavy-metal residue

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] The synthesis of embodiment 1 abiraterone acetate

[0046] (1) Hydroxyl protection

[0047] Dissolve 10.0 g of dehydroepiandrosterone in 80 ml of THF, add 3.5 g of 3,4-dihydro-2H-pyran (DHP) under stirring at room temperature, and add 0.5 ml of trifluoroacetic acid as a catalyst, and stir the reaction solution at room temperature for 10- 12h.

[0048] The reaction solution was desolvated under reduced pressure, the residue was dissolved in 100ml of water and 100ml of ethyl acetate, separated, the water phase was extracted twice with 50ml of ethyl acetate each time, the ethyl acetate phase was combined, washed once with 150ml of water, 150ml of saturated brine was washed once, dried with anhydrous sodium sulfate, and then precipitated to obtain 11.5g of the product (yield 89%), which can be directly used in the next step without purification.

[0049] (2) Aldol reaction

[0050] 10.0 g of THP-protected dehydroepiandrosterone was dissolved in 50 ml of THF after anhydro...

Embodiment 2

[0061] The synthesis of embodiment 2 abiraterone acetate

[0062] (1) Hydroxyl protection

[0063] Dissolve 10.0 g of dehydroepiandrosterone in 80 ml of THF, add 4.5 g of trimethylchlorosilane (TMSCl) while stirring at room temperature, and add 7.5 ml of triethylamine as an acid-binding agent, and stir the reaction solution at room temperature for 10-12 hours.

[0064] The reaction solution was desolvated under reduced pressure, the residue was dissolved in 100ml of water and 100ml of ethyl acetate, separated, the water phase was extracted twice with 50ml of ethyl acetate each time, the ethyl acetate phase was combined, washed once with 150ml of water, Wash once with 150ml of saturated saline, dry with anhydrous sodium sulfate, and remove the solvent to obtain 12.1g of the product (yield: 97%), which can be directly used in the next step without purification.

[0065] (2) Aldol reaction

[0066] 10.0 g of THP-protected dehydroepiandrosterone was dissolved in 50 ml of THF aft...

Embodiment 3

[0077] The synthesis of embodiment 3 abiraterone acetate

[0078] (1) Hydroxyl protection

[0079] Dissolve 10.0 g of dehydroepiandrosterone in 80 ml of DMF, add 6.3 g of trimethylchlorosilane (TBSCl) while stirring at room temperature, and add 3.3 g of imidazole as an acid-binding agent, and stir the reaction solution at room temperature for 10-12 hours.

[0080] The reaction solution was poured into 100ml of water, the phases were extracted three times with 50ml of ethyl acetate each time, the ethyl acetate phases were combined, washed once with 150ml of water, once with 150ml of saturated brine, dried with anhydrous sodium sulfate, and desolvated to obtain The crude product was 13.5g, which was quickly purified by thin-layer silica gel cake to obtain 12.8g (yield 92%), which could be used in the next reaction.

[0081] (2) Aldol reaction

[0082] 12.0 g of THP-protected dehydroepiandrosterone was dissolved in 50 ml of THF after anhydrous treatment, and pre-cooled for use....

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Abstract

The invention discloses a novel method for preparing abiraterone acetate. The method comprises the following steps of: hydroxyl protection, Aldol reaction, dehydration reaction, deprotection and acetylation. According to the method, the heavy-metal reagent, the strict anhydrous and anaerobic equipment and the expensive alkyl boron reagent are not used, thus the cost is reduced greatly. The method is suitable for mass industrial production.

Description

technical field [0001] The invention relates to a preparation method of chemicals, in particular to a preparation method of abiraterone acetate. Background technique [0002] Abiraterone acetate, the chemical name is 17-(3-pyridyl)androst-5,16-diene-3beta-ethanol ester, the molecular structure is shown in the following formula: [0003] [0004] Abiraterone acetate is converted into abiraterone in the body. Abiraterone is an androgen synthesis inhibitor that can inhibit 17α-hydroxylase / C17,20-lyase (CYP17), which is expressed in testis, adrenal gland and prostate tumor tissue It is expressed in and is necessary for the biosynthesis of androgens. [0005] The growth of prostate cancer cells requires the supply of male hormones, and patients can be removed by surgery or radiotherapy. The goal of treatment is to prevent the testicles from making testosterone and other male hormones, and one option is surgical removal of the testicles. Another treatment option is to use dr...

Claims

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Application Information

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IPC IPC(8): C07J43/00
CPCY02P20/55
Inventor 刘珂牟英波郎跃武
Owner SUZHOU LEINA PHARMA RES DEV
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