Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation method of ranolazine

A technology of ranolazine and piperazine, applied in the field of preparation of ranolazine, can solve the problems of complicated processing, high risk, waste of piperazine and the like, and achieve the effects of simplifying process steps, reducing costs and improving yields

Active Publication Date: 2013-04-17
QILU PHARMA HAINAN +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above two methods all have the disadvantages of complex post-reaction treatment, low yield, waste of piperazine, etc.
At present, the first method is more researched at home and abroad, but in the first method, an excessive amount of piperazine is used to synthesize the intermediate to prevent the generation of too many by-products. Not only that, but the post-treatment process in this step In the process, the low boiling point solvent of diethyl ether (CN200810070833; CN200610152726) is used, which is risky and not suitable for industrial 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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of ranolazine
  • Preparation method of ranolazine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Add 37g piperazine hydrochloride salt in the reaction bottle that 150ml 95% ethanol is housed, add dropwise 8mol / L sodium hydroxide solution 40ml while stirring, add 20g 2-chloro-N-(2,6- Xylyl)acetamide was heated to reflux, and after 1.5 hours of reaction, TLC monitored that the reaction was complete, and the heating was stopped. After cooling down to room temperature, add 35ml of concentrated hydrochloric acid dropwise to adjust the pH to 3-4, filter with suction, add 200ml of dichloromethane to the filtrate, add 60ml of 4mol / L sodium hydroxide solution dropwise while stirring, adjust the pH to 11-12, and separate the liquids , the aqueous layer was extracted twice with 100ml of dichloromethane respectively, the organic phases were combined, and the organic phase was washed twice with 80ml of water respectively, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure to obtain 21.4g of off-white granular intermediates, Yield 85.6%.

[00...

Embodiment 2

[0024] Add 39g of piperazine hydrochloride salt into the reaction flask containing 150ml of 95% ethanol, add dropwise 55ml of 6mol / L sodium hydroxide solution while stirring, and add 20g of 2-chloro-N-(2,6- Xylyl)acetamide was heated to reflux, and after 1.5 hours of reaction, TLC monitored that the reaction was complete, and the heating was stopped. After cooling down to room temperature, add 35ml of concentrated hydrochloric acid dropwise to adjust the pH to 3-4, filter with suction, add 200ml of dichloromethane to the filtrate, add 60ml of 4mol / L sodium hydroxide solution dropwise while stirring, adjust the pH to 11-12, and separate the liquids , the aqueous layer was extracted twice with 100ml of dichloromethane, the organic phases were combined, and the organic phase was washed twice with 80ml of water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure to obtain 21.2 g of off-white granular intermediates. Yield 84.8%

[0025] After dis...

Embodiment 3

[0027] Add 35g of piperazine hydrochloride salt into the reaction flask containing 150ml of 95% ethanol, add 70ml of 4mol / L sodium hydroxide solution dropwise while stirring, and add 20g of 2-chloro-N-(2,6- Xylyl)acetamide was heated to reflux, and after 2 hours of reaction, TLC monitored that the reaction was complete, and the heating was stopped. After cooling down to room temperature, add 35ml of concentrated hydrochloric acid dropwise to adjust the pH to 3-4, filter with suction, add 200ml of dichloromethane to the filtrate, add 60ml of 4mol / L sodium hydroxide solution dropwise while stirring, adjust the pH to 11-12, and separate the liquids , the aqueous layer was extracted twice with 100ml dichloromethane respectively, the organic phases were combined, and the organic phase was washed twice with 80ml water respectively, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure to obtain 21.0 g of off-white granular intermediates, Yield 84.1%. ...

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 preparation method of ranolazine. The method comprises the following steps: adding piperazine hydrochloride in 95% ethanol used as the solvent, dropping a sodium hydroxide solution under stirring, adding 2-chloro-N-(2,6-dimethylphenyl)acetamide after the feed liquid is clear, and then heating to react in a refluxing state and generate an intermediate 2-piperazine-N-(2,6-dimethylphenyl)acetamide; and then adding hydrochloric acid to adjust the pH value, performing suction filtering, adjusting the pH value back with an inorganic alkali, extracting with an extraction solvent, rinsing, drying, evaporating the solvent under reduced pressure to obtain an off-white solid granular intermediate, and then reacting with 1-(2-methoxyphenoxy)-2,3-propylene oxide to generate ranolazine. The preparation method has fewer steps and higher yield; the content of ranolazine is up to more than 99.9% without further refining after the synthesis of ranolazine; and the cost is reduced.

Description

technical field [0001] The invention relates to a preparation method of ranolazine, which belongs to the technical field of medicine. Background technique [0002] Ranolazine, Chinese chemical name: N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazinyl}B amides. [0003] Structural formula: [0004] [0005] Ranolazine is a new type of drug for the treatment of angina-type coronary heart disease developed by CV Therapeutics of the United States. It is a pFOX (partial fatty acid oxidase) inhibitor, which reduces the oxygen demand of the heart by changing the way of heart metabolism. Cardiac metabolism is the production of fatty acids or glucose using oxygen. Under normal physiological conditions, cardiomyocytes mainly use fatty acid oxidation energy, and less use of glucose. pFOX inhibitors can reduce fatty acid oxidation and thereby increase glucose oxidation. Since per unit of oxygen utilizes more glucose metabolic capacity than fatty acid me...

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 Patents(China)
IPC IPC(8): C07D295/15
Inventor 常宝磊秦春霞李卓华李保勇吴柯张兆珍董廷华
Owner QILU PHARMA HAINAN
Features
  • R&D
  • 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