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Preparation method of abiraterone acetate

A technology of abiraterone acetate and alcohol acetate, which is applied in the field of preparation of abiraterone acetate, can solve the problems of production cost, reaction yield and insufficient discharge of three wastes, and achieve the promotion of economic and technological development, easy post-processing and purification, The effect of high chemoselectivity

Active Publication Date: 2013-08-14
临沂经开财金投资发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] In summary, although the preparation method of abiraterone acetate involved in the current published literature reports has been optimized and improved in the reaction sequence, coupling reaction catalyst, 3-pyridyl side chain selection and activation method, However, these synthetic routes still have deficiencies in terms of production cost, reaction yield and waste discharge.

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Add 17-halogen-androst-5,16-dien-3β-alcohol acetate (II) (4.4g, 10mmol), 3-pyridineboronic acid pinacacate (III) (2.25g, 11mmol) into the reaction flask , Potassium acetate (1.2g, 12mmol), 50mL of dimethyl sulfoxide, heated up to 40°C, and stirred until the system was dissolved uniformly. Under the protection of nitrogen, 1,1'-bis(diphenylphosphino)ferrocene nickel chloride (0.18g, 2.5%eq) was added, the temperature was raised to 80°C, and the reaction was continued for 5 hours, and the reaction was detected by TLC. The solvent was recovered under reduced pressure. The residue was dissolved in dichloromethane and water, and the aqueous layer was separated, washed successively with 10% sodium carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. Dichloromethane was recovered under reduced pressure, and the residue was recrystallized from ethyl acetate and n-hexane to obtain 3.64 g of abiraterone acetate (I), with a yield of 93.1%.

Embodiment 2

[0036]Add 17-halogen-androst-5,16-dien-3β-alcohol acetate (II) (4.4g, 10mmol), 3-pyridineboronic acid pinacacate (III) (2.25g, 11mmol) into the reaction flask , potassium carbonate (1.66g, 12mmol), N,N-dimethylformamide 50mL and water 10mL, warm up to 40°C, and stir until the system is uniformly dissolved. Under nitrogen protection, bis(triphenylphosphine)palladium chloride (0.19 g, 2.5% eq) was added, the temperature was raised to 80° C., and the reaction was continued for 8 hours, and the reaction was detected by TLC. The solvent was recovered under reduced pressure. The residue was dissolved in dichloromethane and water, and the aqueous layer was separated, washed successively with 10% sodium carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. Dichloromethane was recovered under reduced pressure, and the residue was recrystallized from ethyl acetate and n-hexane to obtain 3.33 g of abiraterone acetate (I), with a yield of 85.2%.

Embodiment 3

[0038] Add 17-halogen-androst-5,16-dien-3β-alcohol acetate (II) (4.4g, 10mmol), 3-pyridineboronic acid pinacacate (III) (2.25g, 11mmol) into the reaction flask , potassium phosphate (2.5g, 12mmol), 50mL of dioxane and 10mL of water, heated up to 40°C, and stirred until the system was dissolved uniformly. Under the protection of nitrogen, tetrakis(triphenylphosphine)palladium (0.29 g, 2.5% eq) was added, the temperature was raised to 80° C., and the reaction was continued for 8 hours, and the reaction was detected by TLC. The solvent was recovered under reduced pressure. The residue was dissolved in dichloromethane and water, and the aqueous layer was separated, washed successively with 10% sodium carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. Dichloromethane was recovered under reduced pressure, and the residue was recrystallized from ethyl acetate and n-hexane to obtain 3.25 g of abiraterone acetate (I), with a yield of 83.1%.

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Abstract

The invention discloses a preparation method of abiraterone acetate (I) having a chemical name of 17-(3-pyridyl)-androstane-5,16-diene-3beta-alcohol acetate. The preparation method comprises the following steps of: taking 17-halogen-androstane-diene-3beta-alcohol acetate (II) and 3-pyridine boronic acid pinacol ester (III) as raw materials, and obtaining the abiraterone acetate (I) through a coupling reaction under the action of a catalyst. The preparation method has the advantages that the process is simple, raw materials are easily available, and quality is controllable; and therefore the preparation method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis method design and preparation of raw materials and intermediates, and in particular relates to a preparation method of abiraterone acetate. Background technique [0002] Abiraterone acetate ((Abiraterone acetate, chemical name 17-(3-pyridyl)-androsta-5,16-dien-3β-alcohol acetate, I) is a kind of oral An effective androgen biosynthesis inhibitor. In 2011, it was approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA), and its trade name is Zytiga. This drug is clinically combined with prednisone (Prednisone) The treatment of metastatic advanced prostate cancer that has developed resistance to traditional hormone therapy can not only reduce the level of prostate specific antigen, but also help shrink tumors and prolong the life of patients with advanced prostate. From the perspective of mechanism of action, this drug also It can be used ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J43/00
Inventor 许学农
Owner 临沂经开财金投资发展有限公司
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