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

Method for synthesizing anastrozole intermediate-2,2'-(5-methyl-1,3-phenylene)-bis-(2-methyl propionitrile)

A technology of anastrozole and methylpropionitrile, applied in the field of compound synthesis, can solve the problems of difficult synthesis of starting materials and low yield of intermediates, and achieve the effect of easy synthesis, high yield, and cheap and easy-to-obtain raw materials

Active Publication Date: 2011-02-16
UNIV OF SCI & TECH OF CHINA
View PDF7 Cites 16 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The use of highly toxic cyanide is inevitable in both methods, and the synthesis of starting materials is difficult, and the yield of the final intermediate is not high, and side reactions will occur to generate impurities.

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 synthesizing anastrozole intermediate-2,2'-(5-methyl-1,3-phenylene)-bis-(2-methyl propionitrile)
  • Method for synthesizing anastrozole intermediate-2,2'-(5-methyl-1,3-phenylene)-bis-(2-methyl propionitrile)
  • Method for synthesizing anastrozole intermediate-2,2'-(5-methyl-1,3-phenylene)-bis-(2-methyl propionitrile)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] (1) Preparation of ethyl 2-cyano-2-methylpropionate

[0057] Add ethyl cyanoacetate (4.52g, 40mmol), DBU (22.07g, 88mmol) and 50mL DMF to a 150ml round bottom flask equipped with a magnet. After stirring in an ice-water bath for 10 minutes, iodomethane (12.49 g, 88 mmol) was slowly added dropwise. After the dropwise addition, the round-bottomed flask was covered with a lid, the ice-water bath was removed, and the reaction was stirred at room temperature for 2 h. After the reaction, the solution in the round bottom flask was transferred to a 250mL separatory funnel, 80mL of ethyl acetate was added, the organic phase was extracted twice with 80mL of water, and once with 80mL of saturated saline. After the extraction, the organic phase was dried with anhydrous magnesium sulfate for 20 minutes, filtered, and the solvent ethyl acetate was removed by a vacuum rotary evaporator, and then separated by a simple chromatographic column to obtain a light yellow liquid with a yield...

Embodiment 2

[0064] (1) Preparation of sodium cyanoacetate

[0065] method 1:

[0066] Sodium hydroxide (1.60 g, 40 mmol) and 50 mL of ethanol were added to a 150 mL round bottom flask equipped with a magnet, and cyanoacetic acid (3.40, 40 mmol) and 30 mL of ethanol were added to another 100 mL round bottom flask. Add the ethanol solution of cyanoacetic acid dropwise to the ethanol solution of sodium hydroxide under stirring, and continue stirring for 20 minutes after the dropwise addition is completed. After the reaction was completed, ethanol and a small amount of water produced were removed by a vacuum rotary evaporator, filtered, and washed three times with a small amount of ether to obtain a white solid with a yield of 98%.

[0067] Method 2:

[0068] Sodium hydroxide (1.60 g, 40 mmol) and 50 mL of ethanol were added to a 150 mL round bottom flask equipped with a magnet, and ethyl cyanoacetate (4.52 g, 40 mmol) and 30 mL of ethanol were added to another 100 mL round bottom flask. ...

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 provides a method for synthesizing an anastrozole intermediate-2,2'-(5-methyl-1,3-phenylene)-bis-(2-methyl propionitrile), which comprises the following steps: dissolving a cyanoacetate derivative and 3,5-dihalogenated toluene in a solvent, carrying out decarboxylation cyanomethylation reaction under the action of a palladium catalyst and an organic phosphorus ligand, obtaining a target product, or obtaining 2,2'-(5-methyl-1,3-phenylene)-bis-(acetonitrile), and further being reacted with halogenated methane or methane which is ready to be halogenated in the presence of a strong base hydride, and generating the target product. The method for synthesizing the intermediate can avoid the use of highly toxic cyanide, and has the advantages of cheap price and easy obtainment of raw materials, easy synthesis, no side reactions and high yield.

Description

technical field [0001] The invention relates to the field of compound synthesis, in particular to a method for synthesizing an anticancer drug anastrozole intermediate 2,2'-(5-methyl-1,3-phenylene)bis(2-methylpropionitrile) . Background technique [0002] The chemical name of Anastrozole is: 2,2'-[5-(1H-1,2,4-triazol-1-yl-methyl)-1,3-phenylene]bis(2 -methylpropionitrile) or a,a,a',a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-diethylcyanobenzene . Its chemical formula is: [0003] [0004] The chemical formula of its synthetic intermediate 2,2'-(5-methyl-1,3-phenylene)bis(2-methylpropionitrile) is: [0005] [0006] Anastrozole is a potent and selective non-steroidal aromatase inhibitor developed by AstraZeneca (AstraZeneca). It is suitable for advanced breast cancer in postmenopausal women who cannot be controlled by tamoxifen and other anti-estrogen therapy, and has high medicinal value. The drug was launched in the UK in September 1995, and the US FDA has...

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): C07C255/33C07C253/30
Inventor 尚睿黄铮傅尧郭庆祥刘磊
Owner UNIV OF SCI & TECH OF CHINA
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com