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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 affecting the industrialization effect, difficult to purify, and reduced yield, so as to promote economic and technological development, obtain raw materials easily, Quality and reliable results

Inactive Publication Date: 2015-05-20
南京广祺医药科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chinese patent No. CN101044155 research points out, because basic catalyst 2,6-di-tert-butyl-4-methylpyridine (DTBMP) is used in the preparation process of triflate, the elimination reaction of acetyl group easily occurs, making The yield is reduced and it is difficult to purify, which affects the industrialization effect of the process
[0016] In summary, although the synthetic route of abiraterone acetate involved in the current published literature reports has been optimized and improved in the reaction sequence, coupling mode, hydroxyl protection and deprotection, its preparation cost, yield There are still many deficiencies in aspects such as waste discharge and three wastes, especially how to reduce reaction steps, improve chemical selectivity and reduce side reactions, which have important practical significance for the economic and technological development of abiraterone acetate raw materials

Method used

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

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Experimental program
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Effect test

Embodiment 1

[0032] Under a nitrogen atmosphere, add 3-bromopyridine (1.88g, 12mmol) and 15mL of anhydrous diethyl ether into a dry reaction flask, cool down to -78°C, add n-butyl lithium in n-hexane solution (2.5M, 5mL) dropwise, and stir React for 45 minutes. Keeping at -78°C, add DHEA (3.3 g, 10 mmol) in 25 mL of tetrahydrofuran solution dropwise to the system for about 30 minutes, then continue the reaction for 30 minutes. Naturally raised to room temperature, the reaction was stirred for 24 hours. At 0°C, the reaction was quenched with saturated ammonium chloride solution, stirred and extracted three times with dichloromethane, the organic phases were combined, washed with water and saturated brine successively, and dried over anhydrous magnesium sulfate. Dichloromethane was recovered under reduced pressure, and the residue was recrystallized from ethyl acetate / n-hexane to obtain 1.74 g of 17-(3-pyridine)-17-hydroxy-androst-5-en-3β-ol acetate (II). The rate is 87.2%.

Embodiment 2

[0034] Under a nitrogen atmosphere, add 17-(3-pyridine)-17-hydroxyl-androst-5-en-3β-ol acetate (II) (2.05g, 5mmol) and toluene 25mL in a dry reaction flask, stir Add methyl N-(triethylammoniumsulfonyl)carbamate (Burgess reagent) (1.28 g, 5 mmol), react at room temperature for 1 hour, raise the temperature to 85° C., and continue the reaction for 1 hour. Add Burgess reagent (1.28 g, 5 mmol), react at room temperature for 1 hour, and continue to react for 1 hour after raising the temperature to 85°C. TLC detects that the reaction is complete. Cool and quench the reaction with ice water. The organic phase was separated, and the aqueous phase was extracted twice with toluene. The organic phases were combined, washed with water and brine in turn, and dried over anhydrous sodium sulfate. Toluene was recovered under reduced pressure, and the residue was recrystallized from methanol / water to obtain 3.0 g of abiraterone acetate (I), with a yield of 90.4%.

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Abstract

The invention discloses a preparation method of abiraterone acetate (I). The preparation method comprises the following steps of: based on dehydroepiandrosterone acetate as a raw material, performing addition reaction with 3-pyridyllithium to generate 17-(3-pyridyl)-17-hydroxy-androst-5-ene-3 beta-ol acetate (II); performing elimination reaction on the intermediate (II) under the action of a Burgess reagent to get abiraterone acetate (I). The preparation method has the advantages of simple process, easiness in obtainment of raw materials and controllable quality, and 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 is 17-(3-pyridyl)-androst-5,16-dien-3β-alcohol acetate, I) is an oral effective drug developed by the U.S. Centocor Oftho company. An androgen biosynthesis inhibitor; in 2011, it was approved for marketing by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA), with the trade name Zytiga. The drug is clinically used in combination with prednisone (Prednisone) to treat metastatic advanced prostate cancer that has developed resistance to traditional hormone therapy. patient's life. Recently, the US Food and Drug Administration and the European Medicines Evaluation Agency also approved the addition of abiraterone acetate indi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J43/00
Inventor 许学农
Owner 南京广祺医药科技有限公司
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