Improved method for preparing valsartan

A valsartan and solvent technology, applied in the field of improved preparation of valsartan, can solve the problems of difficult large-scale industrial production, high content of optical isomers, long diazo reaction time, etc., to reduce pollution and produce The effect of high purity and short reaction time

Inactive Publication Date: 2012-07-18
安徽现代天然生物有限公司
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the preparation method of U.S. Patent No. 5,399,578A, in the step of diazotization, the catalyst it uses is tributyltin chloride, and the reaction time is more than 40 hours. Since the catalyst contains tin, the residual tin will be brought to the final products, and the content exceeds the requirements of ICH, and organotin is a highly toxic compound, which is very difficult to control;
[0004] In Chinese Patent Publication Nos. CN101270096A and CN101817795A, the diazotization has been optimized and improved respectively, not only canceling the use of organotin compounds...

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

example 1

[0025] An improved method for preparing valsartan,

[0026] 1. Synthesis of crude valsartan: Add 13 grams of (N-(1-pentanoyl)-N-[4-[2-(5-cyano)-phenyl]benzyl]-L - Methyl valine, 1.2 grams of triethylamine hydrochloride, 23 grams of sodium azide and 200 milliliters of xylene, the oil bath is heated to 100°C-120°C, and the reaction is kept for 2-3 hours, and the reaction is controlled by thin-layer chromatography At the end point, the compound N-(1-pentanoyl)-N-[4-[2-(1H-tetrazol-5-yl)phenyl]benzyl]-L-valine methyl ester can be obtained after the reaction , lower the temperature to 30°C-35°C, add 200 ml of 13-14% sodium hydroxide aqueous solution, and keep the reaction at 60°C-65°C for 3 hours, control the end point of the reaction by thin-layer chromatography, adjust the reactant with an appropriate amount of concentrated hydrochloric acid PH = 1-2, a large amount of solids precipitated, add 130 ml of dichloromethane to dissolve the solids, let stand to separate layers, take t...

example 2

[0028] Example two: An improved method for preparing valsartan,

[0029] 1. Synthesis of crude valsartan:

[0030] Add 130 grams of (N-(1-pentanoyl)-N-[4-[2-(5-cyano)-phenyl]benzyl]-L-valine methyl ester in a three-necked glass bottle, 12 gram of triethylamine hydrochloride, 230 grams of sodium azide and 2000 milliliters of toluene, the temperature of the oil bath is raised to 100°C-110°C, and the reaction is kept for 2-3 hours. The end point of the reaction is controlled by thin-layer chromatography, and the compound N can be obtained after the reaction is completed. -(1-pentanoyl)-N-[4-[2-(1H-tetrazol-5-yl)phenyl]benzyl]-L-valine methyl ester, cool to 30°C-35°C, Add 2,000 ml of 13%-14% sodium hydroxide aqueous solution to the reaction system, keep the reaction at 60°C-65°C for 2.5 hours, control the end point of the reaction by thin-layer chromatography, adjust the pH of the reactant to 1 with an appropriate amount of concentrated hydrochloric acid -2, a large amount of ...

example 3

[0032] Example three: an improved method for preparing valsartan,

[0033] 1. Synthesis of crude valsartan:

[0034] Add 500 grams of (N-(1-pentanoyl)-N-[4-[2-(5-cyano)-phenyl]benzyl]-L-valine methyl ester, 46.2 gram of triethylamine hydrochloride, 885 grams of sodium azide and 7692 milliliters of toluene, the temperature of the oil bath is raised to 110°C-120°C, and the reaction is kept for 2-3 hours. The end point of the reaction is controlled by thin-layer chromatography, and the compound N can be obtained after the reaction is completed. -(1-pentanoyl)-N-[4-[2-(1H-tetrazol-5-yl)phenyl]benzyl]-L-valine methyl ester, cool to 60°C-65°C, Add 7692 ml of 13%-14% sodium hydroxide aqueous solution, keep the temperature at 60°C-65°C for 3 hours, control the end point of the reaction by thin-layer chromatography, adjust the pH of the reactant to 1-2 with an appropriate amount of concentrated hydrochloric acid, when When a large amount of solids are precipitated in the solution, ...

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 an improved method for preparing valsartan. According to the invention, certain steps required for preparing the valsartan in certain patents in the past are improved. The improved method comprises the following steps of: adding (N-(1-valeryl)-N-[4-[2-(5-cyan)-phenyl]benzyl]-L-valine methyl ester valsartan, sodium azide, triethylamine hydrochloride and a solvent into a reactor, and directly performing diazotization reaction; adding a sodium hydroxide solvent for saponification reaction after the diazotization reaction; and purifying the obtained product to finally obtain the valsartan product with high purity. According to the method, the diazotization reaction time is short, the loss of energy is reduced, the reaction process is environment-friendly, the yield and the purity of the product are high, the industrial production cost is greatly reduced, and the industrial production is easily realized.

Description

technical field [0001] The invention relates to the field of fine chemicals, in particular to an improved method for preparing valsartan. Background technique [0002] Valsartan is an orally effective and specific angiotensin II (AT1) receptor antagonist that selectively acts on AT1 receptor subtypes, blocking the combination of Ang II and AT1 receptors to inhibit vasoconstriction and the release of aldosterone, resulting in a hypotensive effect. It was successfully developed by the Swiss Novartis company, first listed in Germany, approved by the US FDA in 1996, and listed in the US in 1997. [0003] In the preparation method of U.S. Patent No. 5,399,578A, in the step of diazotization, the catalyst it uses is tributyltin chloride, and the reaction time is more than 40 hours. Since the catalyst contains tin, the residual tin will be brought to the final products, and the content exceeds the requirements of ICH, and organotin is a highly toxic compound, which is very difficu...

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): C07D257/04
Inventor 沈仕群
Owner 安徽现代天然生物有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap