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

17-(3-pyridyl)-androstane-5,16-diene-3 beta-ol synthetic method

A synthetic method and pyridyl-based technology, applied in the direction of steroids, organic chemistry, etc., can solve the problems of harsh conditions, long reaction time, and high activity of iodides, and achieve the effects of mild reaction conditions, low production costs, and cheap raw materials

Inactive Publication Date: 2017-11-07
李建恒
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] This route has the following disadvantages: (1) the reaction time is long and the yield is low; (2) it is easy to generate polymer impurities that are difficult to remove during the coupling reaction
[0005] The second is to change diethyl-(3-pyridyl)borane to be 3-pyridine zinc bromide, and carry out coupling condensation with 17-iododehydroepiandrosterone under the action of a catalyst. Disadvantages of high resulting in difficult-to-remove polymer impurities
[0006] The third route is to change diethyl-(3-pyridyl) borane as a Grignard reagent, directly react with dehydroepiandrosterone at low temperature, and then obtain abiraterone by elimination reaction, which produces The rate is high, but the conditions are relatively harsh, requiring a low temperature of -78°C, and has certain dangers, so it is not suitable for industrial mass production

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] A kind of synthetic method of 17-(3-pyridyl)-androst-5,16-dien-3β-alcohol, comprises the steps:

[0022] A. Add 0.95g (5mmol) p-toluenesulfonyl chloride and 15mL toluene to a 100ml round-bottomed flask in turn, stir and dissolve thoroughly to obtain solution X, slowly add the amount according to the substance at 15°C (solution X is cooled to 15°C) Add 1.5mL (10mmol) 80% hydrazine hydrate to solution X at a ratio of 1:2, drop it within 5 minutes; continue to react for 30 minutes, and a white precipitate appears in the flask. TLC analysis confirmed the reaction endpoint. After completion of the reaction, add 30ml of cold water at 10°C, stir, filter with suction, wash the filter cake 3-5 times with purified water, and dry to obtain 0.82g of white p-toluenesulfonyl hydrazide crystals, with a yield of 86.3% (document value: yield rate of 92%).

[0023] B, the synthesis of dehydroepiandrosterone-17-p-toluenesulfonylhydrazone

[0024] Add 0.75g (3mmol) dehydroepiandrosteron...

Embodiment 2

[0028] A. Add 1.02g (5.3mmol) p-toluenesulfonyl chloride and 15mL toluene to a 100ml round-bottomed flask in sequence, stir and dissolve thoroughly to obtain solution X, slowly add 1.7mL (12mmol) 80% hydrazine hydrate dropwise to the solution at 15°C In X, the dripping was completed within 5 minutes; the reaction was continued for 30 minutes, and a white precipitate appeared in the flask. TLC analysis confirmed the reaction endpoint. After completion of the reaction, add 30ml of 10°C water to stir, filter with suction, wash the filter cake 3-5 times with purified water, and dry to obtain 0.93g of white p-toluenesulfonyl hydrazide crystals, with a yield of 86.7% (literature value: yield 92%).

[0029] B, the synthesis of dehydroepiandrosterone-17-p-toluenesulfonylhydrazone

[0030] Add 0.97g (3mmol) dehydroepiandrosterone, 25mL methanol, and 1.08g p-toluenesulfonylhydrazide to a 100ml round-bottomed flask in sequence, stir and dissolve at room temperature, add 0.1mL 0.2mol·L ...

Embodiment 3

[0034]A. Add 1.08g (5.7mmol) p-toluenesulfonyl chloride and 15mL toluene to a 100ml round-bottomed flask in turn, stir and dissolve thoroughly to obtain solution X, slowly add 1.8mL (13mmol) 80% hydrazine hydrate dropwise to the solution at 15°C In X, the dripping was completed within 5 minutes; the reaction was continued for 30 minutes, and a white precipitate appeared in the flask. TLC analysis confirmed the reaction endpoint. After completion of the reaction, add 30ml of 10°C water to stir, filter with suction, wash the filter cake 3-5 times with purified water, and dry to obtain 0.94g of white p-toluenesulfonyl hydrazide crystals, with a yield of 85.6% (literature value: yield 92%).

[0035] B, the synthesis of dehydroepiandrosterone-17-p-toluenesulfonylhydrazone

[0036] Add 1.18g (3.3mmol) dehydroepiandrosterone, 25mL methanol, and 1.28g p-toluenesulfonyl hydrazide to a 100ml round-bottomed flask in turn, stir and dissolve at room temperature, add 0.1mL 0.2mol·L -1 Su...

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 discloses a 17-(3-pyridyl)-androstane-5,16-diene-3 beta-ol synthetic method. According to the synthetic method, dehydroepiandrosterone is utilized as a raw material to be condensed with p-toluenesulfonhydrazide and generate coupling reaction with 3-bromopyridine to synthesize a target product of 17-(3-pyridyl)-androstane-5,16-diene-3 beta-ol (abiraterone). The synthetic method has the advantages of moderate reaction condition, low-price and easily available raw material and lower production cost.

Description

technical field [0001] The invention relates to a synthesis method of 17-(3-pyridyl)-androst-5,16-dien-3β-ol. Background technique [0002] Abiraterone is an oral inhibitor of cytochrome oxidase P450 (CYP450) c17, which reduces androgen levels by inhibiting the key enzyme in androgen synthesis - CYP450c17, and has effects on androgen in the testis and other parts of the body Inhibition, used for the treatment of advanced prostate cancer, it can significantly reduce the level of prostate specific antigen in patients with prostate cancer, and will not appear symptoms such as adrenal insufficiency. For patients with prostate cancer, the hormone testosterone can stimulate tumor growth, drugs Or surgery to reduce testosterone production or block the effects of testosterone. But even with low testosterone levels, prostate cancer can continue to grow. Abiraterone targets and inhibits the activity of the enzyme cytochrome P45017A1, which regulates testosterone production, reducing...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07J43/00
CPCC07J43/003
Inventor 李建恒马思跃
Owner 李建恒
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