Method for preparing cardiotonic drug LCZ696

A biphenyl, solid technology, applied in the field of preparation of pharmaceutical compounds, can solve the problems of high content, low purity of LCZ696, difficult to remove, etc.

Active Publication Date: 2015-08-26
BEIJING BOQUANJIAN PHARMA TECH CO LTD
View PDF9 Cites 35 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0025] The disadvantage of the above preparation method is that the obtained LCZ696 has low purity, and the impurities include (2R,4S)-5-biphenyl-4-yl-4-(3-carboxypropionylamino)-2-methyl-pentane Acid, ethyl (2R,4S)-5-biphenyl-4-yl-4-(2,5-dioxopyrrolidin-1-yl)-2-methylpentanoate, the content of both is high, And it is difficult to remove. Although the content of LCZ696 obtained by the above-mentioned prior art can be greater than 98.5%, the content of the above-mentioned two related impurities is greater than 0.3%, which affects the quality of the product. improvement of

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 preparing cardiotonic drug LCZ696
  • Method for preparing cardiotonic drug LCZ696
  • Method for preparing cardiotonic drug LCZ696

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Preparation of LCZ696

[0059] step 1,

[0060] Add 10g (2R,4S)-5-([1,1'-biphenyl]-4-yl)-4-amino-2-methylpentanoic acid hydrochloride and 60ml absolute ethanol into the reaction flask, stir Raise the temperature to 65-70°C; keep at 65-70°C, drop 5.6g of thionyl chloride into the reaction bottle under stirring; after the addition, keep stirring at 65-70°C for 3 hours; check the reaction with TCL (if the reaction is not complete, then Add an appropriate amount of thionyl chloride); after the reaction is completed, the solvent is evaporated under reduced pressure, and the temperature is 50°C, and steamed until no liquid flows out; 100ml of n-heptane is added to the residue, stirred and crystallized at room temperature for 1 hour; the temperature is lowered to 0~ Stir and crystallize at 10°C for 2 hours; filter, rinse the filter cake with 50ml of n-heptane, and dry in vacuum for 4 hours at a temperature of 50-55°C; obtain 10.8g of (2R,4S)-5-([1,1'- Biphenyl]-4-yl)-4-amino...

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 relates to a preparation method of a pharmaceutical compound and particularly relates to a method for preparing a cardiotonic drug LCZ696. Particularly the synthetic route of the compound is as shown in the specification.

Description

technical field [0001] The invention relates to a preparation of a pharmaceutical compound, in particular to a preparation method of an anti-heart failure drug LCZ696. Background technique [0002] LCZ696, the chemical structure is as follows [0003] [0004] LCZ696 is a dual angiotensin receptor type 2 (AT II) and neprilysin inhibitor, consisting of valsartan and the NEP inhibitor drug sacubitril in a 1:1 ratio. The chemical name is as follows: [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propanoic acid-(S)-3'- Methyl-2'-(pentanoyl{2"-(tetrazole-5-ylate)biphenyl-4'-ylmethyl}amino)butanoic acid]trisodium hemipentahydrate. [0005] As a combined substance, valsartan is an angiotensin receptor antagonist, which can be used for various types of hypertension, and has a better protective effect on the heart, brain and kidney. Hypertensive patients such as myocardial infarction, heart failure, proteinuria, and diabetes can be used routinely, and can b...

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): C07D257/04C07C233/51C07C231/24C07C231/02C07C229/34
CPCC07C227/18C07C231/02C07C231/24C07D257/04C07C233/51C07C229/34
Inventor 王浩宇
Owner BEIJING BOQUANJIAN PHARMA TECH CO LTD
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