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

Preparation method of candesartan cilexetil

A technology of candesartan cilexetil and sartan cilexetil, which is applied in the field of drug synthesis, can solve the problems of high production risk factor and cumbersome operation, and achieve the effects of optimizing reaction conditions, simple operation, and simplified post-reaction treatment operations

Pending Publication Date: 2020-11-10
珠海润都制药股份有限公司
View PDF11 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] In the prior art, after the deprotection reaction of the trityl candesartan cilexetil is complete, the high-purity candesartan cilexetil is obtained through refining, and then the candesartan cilexetil of crystal form I is prepared by crystallization. However, the operation is cumbersome, or the solvent used has a high risk factor in industrial production. It is of great significance to study the reaction and post-treatment in order to obtain a safe and low-cost process.

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 candesartan cilexetil
  • Preparation method of candesartan cilexetil
  • Preparation method of candesartan cilexetil

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1 Preparation of candesartan cilexetil

[0060] Add 210g methanol and 140g trityl candesartan cilexetil into the reaction flask, reduce the temperature to 0-5°C, add 340g sulfuric acid methanol solution (315g methanol, 25g concentrated sulfuric acid), and continue the reaction after dropping the temperature at 0-5°C 4h, after the completion of the reaction, add 200 g of dichloromethane to the reaction solution, adjust pH>5 with saturated sodium bicarbonate solution, separate the liquids to obtain the dichloromethane layer, and concentrate to obtain an oily substance. Add 300g of acetone to the oil, slowly add 220g of drinking water at 50°C, and precipitate solids. Control the temperature at 45°C-50°C and stir and crystallize for 3h, cool to 20°C, crystallize for 2h, filter and dry to obtain 95g candesartan Ester, the yield is 95%, the purity is 99.29%, and the trityl alcohol is 0.19%.

Embodiment 2

[0061] Example 2 Preparation of candesartan cilexetil

[0062] Refer to the preparation method of Example 1, in which 500 g of sulfuric acid solution (440 g of methanol, 30 g of concentrated sulfuric acid), 285 g of acetone, 215 g of water, 93% yield, 99.52% purity, and 0.22% trityl alcohol.

Embodiment 3

[0063] Example 3 Preparation of candesartan cilexetil

[0064] With reference to the preparation method of Example 1, the sodium bicarbonate solution was replaced with potassium carbonate solution, the amount of acetone was 300 g, the amount of water was 250 g, the yield was 96%, the purity was 99.47%, and the trityl alcohol was 0.30%.

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 candesartan cilexetil. The preparation method comprises the following steps: dissolving triphenylmethyl candesartan cilexetil in an alcohol solvent, adding a sulfuric acid-methanol solution at low temperature, adding halogenated hydrocarbon into a reaction solution after the reaction is finished, regulating the pH value of the reaction solution by using an aqueous alkaline solution, separating an organic layer, and conducting concentrating; and adding acetone into a concentrate obtained in the previous step, adding water, and conducting crystallizing; According to the method, reaction conditions and post-treatment conditions are optimized, operation is simplified, impurities can be effectively removed, and the method is low in cost, safe tooperate and suitable for industrial production.

Description

Technical field [0001] The invention belongs to the field of drug synthesis, and relates to a preparation method of candesartan cilexetil, in particular to the preparation of candesartan cilexetil from triphenyl candesartan cilexetil. Background technique [0002] Candesartan cilexetil is a good active ingredient of antihypertensive drugs. Candesartan medoxomil, as a prodrug form, is absorbed in the body through the intestine, and is completely hydrolyzed into the active metabolite of Candesartan, which binds to the angiotensin II subtype I receptor (AT1) with high selectivity. Produce anti-hypertensive effect, and its structure is shown in formula I below. [0003] [0004] The method of patent EP459136 is widely used. This method takes 2-tert-butoxycarbonylamino-3-nitrobenzoic acid ethyl ester as raw material, and forms 2-ethoxybenzimidazole through N-alkylation, de-tert-butoxycarbonyl protective group, reduction and cyclization. The ring is tetrazolyzed, hydrolyzed, trityl-pr...

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): C07D403/10A61P9/12
CPCC07D403/10A61P9/12
Inventor 张榕芳蔡强李厚俭覃志俊
Owner 珠海润都制药股份有限公司
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