Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for separating and purifying abiraterone and dimer of the abiraterone

A technology of abiraterone and dimer, which is applied in the field of biomedicine, can solve the problems of the uncertainty of the purity of the final product, the absence of high-purity abiraterone dimer, and the unsatisfactory removal effect of abiraterone dimer. To achieve the effect of reducing the difficulty of refining

Active Publication Date: 2020-11-03
济南立德医药技术有限公司
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The main impurity produced in the reaction process is abiraterone dimer. The purification method described in the patent US5604213 is not ideal for removing abiraterone dimer. The content of abiraterone dimer is purified to the standard requirements, resulting in many uncertainties in the purity of the final product, which in turn affects the safety of the drug
[0006] In addition, as abiraterone dimer is a main impurity in the synthesis process of abiraterone, the acquisition and purity of its standard substance are of great significance for the synthesis research of abiraterone. At present, there is almost no information on how to obtain high-purity abiraterone Research Report on Dragon Dimer

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for separating and purifying abiraterone and dimer of the abiraterone
  • Method for separating and purifying abiraterone and dimer of the abiraterone
  • Method for separating and purifying abiraterone and dimer of the abiraterone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] A method for separating and purifying abiraterone and dimers thereof, comprising the following steps:

[0024] (1) Dissolve 98g (0.246mol) 17-iodo-androst-5,16-diene-3β-ol in 1.1LTHF in a 2L reaction flask, add 1.73g (0.0025mol) bistriphenylphosphine dichloride Palladium chloride and 43.35g (0.295mol) diethyl (3-pyridyl) borane, then in this reaction solution, add the K of 2M 2 CO 3 500ml of aqueous solution was heated to reflux for 4 days, the residual amount of 17-iodo-androst-5,16-dien-3β-ol was monitored by HPLC <0.5%, and the reaction was stopped to obtain the abiraterone reaction solution.

[0025] (2) Cool down to 15°C, continue to stir for 2h at this temperature, filter to obtain wet product filter cake I3.2g

[0026] (3) Put filter cake I and 0.32g gac into 32ml tetrahydrofuran and heat up and reflux for 30min, heat filter to obtain filtrate II and filter cake II;

[0027] (4) The filtrate II was concentrated to dryness under reduced pressure to obtain a res...

Embodiment 2

[0030] A method for separating and purifying abiraterone and dimers thereof, comprising the following steps:

[0031] (1) The process of obtaining the abiraterone reaction solution is the same as in Example 1.

[0032] (2) Cool down to 20°C, continue to stir for 2h at this temperature, filter to obtain wet product filter cake I2.9g

[0033] (3) Put filter cake I and 0.29g activated carbon into 32ml THF and heat up to reflux for 30min, heat filter to obtain filtrate II and filter cake II;

[0034] (4) The filtrate II was concentrated to dryness under reduced pressure to obtain 2.3 g of residue.

[0035] (5) Add 4.6ml of tetrahydrofuran to the obtained residue, raise the temperature to reflux, stir to dissolve, drop to 10°C, stir and crystallize for 3h, and filter to obtain 1.9g of the target product abiraterone dimer with a purity of 99.38%.

Embodiment 3

[0037] A method for separating and purifying abiraterone and dimers thereof, comprising the following steps:

[0038] (1) The process of obtaining the abiraterone reaction solution is the same as in Example 1.

[0039] (2) Cool down to 18°C, continue to stir for 3h at this temperature, filter to obtain wet product filter cake I2.7g

[0040] (3) Put filter cake I and 0.27g gac into 274ml tetrahydrofuran, heat up and reflux for 30min, heat filter, get filtrate II and filter cake II;

[0041] (4) The filtrate II was concentrated to dryness under reduced pressure to obtain 2.3 g of residue.

[0042] (5) Add 11.5ml of tetrahydrofuran to the obtained residue and raise the temperature to reflux, stir to dissolve, drop to 5°C, stir and crystallize for 2.5h, and filter to obtain 1.86g of the target product abiraterone dimer with a purity of 99.56%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to a method for separating and purifying abiraterone and a dimer of the abiraterone, which is characterized in that impurities are directly separated from a reaction solution at a specific crystallization temperature by utilizing different solubility properties of the impurities and a product, and the impurities are purified to obtain high-purity dimer impurities. Meanwhile, impurities in the reaction mother liquor are separated, so that the content of related substances in a subsequently obtained crude product is greatly reduced, a powerful support is provided for a subsequent refining process, the refining difficulty is reduced to a great extent, and a foundation is laid for obtaining high-purity abiraterone.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a method for separating and purifying abiraterone and its dimer. Background technique [0002] Abiraterone acetate, chemically named 3β-acetoxy-17-(3-pyridyl)-androsta-5,16-diene, inhibits steroid (class) 17α-hydroxylase / C17 -20 lyase (P450c17) to prevent testosterone production. An orally effective irreversible inhibitor of CYP17 enzyme developed by Cancer Research UK and BTG for the treatment of prostate cancer and other testosterone-related diseases. The global development and commercialization rights of this product have been transferred to Cougar Biotechnology. In April 2011, it was approved by the US FDA for marketing, and it is clinically used in combination with prednisone to treat castration-resistant prostate cancer (CRPC). This product is a selective oral inhibitor of the key enzyme 17α-hydroxylase-C17, 20-lyase in testosterone synthesis, which can r...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07J43/00
CPCC07J43/003
Inventor 苏广礼陈祝功
Owner 济南立德医药技术有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com