Method for purifying abiraterone acetate

A technology of abiraterone acetate and a purification method is applied in the field of purification of abiraterone acetate to achieve the effects of simplifying purification process, simple operation and time saving

Active Publication Date: 2015-03-25
SHENZHEN KEXING PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there is a certain effect on purification, the obtained product still has more than 1% impurities

Method used

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  • Method for purifying abiraterone acetate
  • Method for purifying abiraterone acetate
  • Method for purifying abiraterone acetate

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preparation example Construction

[0033] For the preparation of crude abiraterone acetate, please refer to patents WO9509178, CN102030798, WO 2006021777, WO 2006021777, WO2006021776, J.Med.Chem.38, 2463-2471, 1995, or refer to patent GB 2282377, Org.Prep.Proced.Int, 1997, 29(l), 123-134, Prep.

[0034] For the salt formation of abiraterone acetate, please refer to the preparation method of WO2006021777 to obtain abiraterone acetate mesylate, abiraterone acetate hydrochloride and abiraterone acetate sulfate; refer to the preparation method of CN201010597372 to obtain abiraterone acetate trifluoromethane Sulfonate; refer to the preparation method of CN201110318824 to obtain abiraterone acetate oxalate, refer to CN201210039644 to obtain abiraterone acetate trifluoroacetate, and refer to CN201210201917 to obtain abiraterone acetate phosphate. These salt-forming methods can all obtain abiraterone acetate salt with better purity.

Embodiment 1

[0035] The selection of the acid used for the salification of abiraterone acetate in embodiment 1

[0036] In WO9320097, each step of column chromatography is used for purification. Since industrial production cannot be realized, some documents (WO2006021776, CN101044155, etc.) mention that the purification can be carried out by salt formation and crystallization, and then the product can be obtained by desalting. With reference to the description of CN102030798, we selected several acids, investigated and selected a suitable acid through the yield of salt formation and the situation of the thin layer chromatography (TLC) plate.

[0037] Table 1 Acid selection

[0038] acid Salt character Yield% oxalic acid Abiraterone Acetate Oxalate White solid 49.7％ phosphoric acid Abiraterone Acetate Phosphate pale yellow solid 50.9％ Methanesulfonic acid Abiraterone Acetate Mesylate yellow solid 52.3 Trifluoromethanesulfonic acid Abirate...

Embodiment 2

[0040] The preparation of embodiment 2 abiraterone acetate hydrochloride

[0041] Add 2.6 kg of crude abiraterone acetate, 11 L of ethyl acetate and 11 L of methyl tert-butyl ether into the reaction kettle, and stir to dissolve. Stir and cool down to 5°C, and add 0.22 kg of concentrated hydrochloric acid dropwise. Stir and crystallize at 0~5°C for 2h. After warming up to room temperature, stir for 1 hour, filter with suction, and rinse the filter cake with methyl tert-butyl ether to obtain a yellow solid. The filter cake was air-dried at 35-40°C for 4 hours to obtain 2.5 kg of off-white solid. Yield: 86.7%, HPLC: 98.3%.

[0042] The high-performance liquid chromatography (HPLC) condition that purity detection is used: get sample appropriate amount, accurately weighed, add acetonitrile to dissolve and dilute to make the solution that contains about 3mg in every 1ml, as need testing solution; According to high-performance liquid chromatography (Chinese Pharmacopoeia 2010 edi...

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Abstract

The invention belongs to the technical field of medicine synthesis, and provides a method for purifying abiraterone acetate. The method comprises the following steps: in the presence of acetic anhydride and organic bases, dissociating abiraterone acetate salt into free abiraterone acetate, wherein the high-performance liquid chromatography (HPLC) purity of dissociated abiraterone acetate is more than 99%; and then refining abiraterone acetate by virtue of acetonitrile recrystallization to obtain abiraterone acetate which has the HPLC purity of more than 99.7% and can meet the medical standards, and ensuring that the content of hydrolysis impurity abiraterone is less than 0.02%. By adopting the method provided by the invention, the problem that inevitable hydrolysis impurity abiraterone exists in a salt dissociation process of abiraterone acetate can be solved, a purification process can be simplified, and reagents can be saved; and moreover, the method is easy to operate, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a method for purifying abiraterone acetate. Background technique [0002] Prostate cancer is a malignant tumor that occurs in male prostate tissue. It is the result of abnormal and disordered growth of prostate acinar cells. European countries have a high incidence of prostate cancer, and the mortality rate is second only to lung cancer. The incidence of prostate cancer in Asian countries is rising rapidly. The incidence rate of prostate cancer has leapt to the third place in male urinary and reproductive system malignancies in my country. Abiraterone acetate is an inhibitor targeting cytochrome CYP17 (17α-hydroxylase / C17,20-lyase), which plays an important role in testosterone production. Abiraterone acetate works by inhibiting cytochrome CYP17 and reducing testosterone production. On April 28, 2011, the U.S. Food and Drug Administration approved abirater...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J43/00
CPCC07J43/003
Inventor 何社辉张水华马鸿杰张英
Owner SHENZHEN KEXING PHARM CO LTD
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