Preparation method of iohexol impurity

A technology of iohexol and compounds, applied in the field of medicinal chemistry, can solve the problems of low yield, shortage of reference substances, high price, etc.

Active Publication Date: 2012-12-12
ZHEJIANG STARRY PHARMA +1
View PDF2 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Since the prior art uses relatively expensive raw materials and processes when preparing the compound of formula (1), and the operation is difficult and the yield is low, the present invention finds a more effective synthetic method after research and solves the problem of the reference substance shortage problem

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 iohexol impurity
  • Preparation method of iohexol impurity
  • Preparation method of iohexol impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1: Preparation of Formula (7) Compound 5-amino-3-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide

[0048] Add formula (8) compound 3-amino-5-(2,3-diacetoxy n-propylcarbamoyl)-2,4,6-triiodobenzoic acid (100g) and 5 times the amount ( V / W) thionyl chloride (500ml), heated to reflux until dissolved, the reaction was completed, concentrated under reduced pressure to recover thionyl chloride, added 3 times the amount (V / W) of chloroform (300ml) into the reaction bottle, cooled to 10-20°C, add water to wash and separate the layers, separate the organic layer, concentrate to dryness under reduced pressure, add 3 times the amount (V / W) of THF (300ml), and pass through excess dry ammonia to make the pH of the reaction solution 10- 12. After the reaction is completed, add an appropriate amount of sodium hydroxide aqueous solution to adjust the pH=14. After hydrolysis at room temperature, cool to 10-20°C to precipitate crystals, filter, and dry to obtain the...

Embodiment 2

[0049] Example 2: Formula (5) compound 5-acetamido-3-N-(2,3-diacetoxypropyl)-2,4,6-triiodo-1,3-phthalamide preparation

[0050] Starting from the compound 5-amino-3-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide of formula (7), the compound Add 30g (47.55mmol) into a 250ml reaction flask, add 120ml of acetic anhydride dropwise, add 0.1g of concentrated sulfuric acid dropwise, and raise the temperature to 65°C-70°C for 26 hours. TLC monitors the complete reaction of the raw materials. Concentrate under reduced pressure to dry to obtain sticky substance formula (5) compound 5-acetamido-3-N-(2,3-diacetoxypropyl)-2,4,6-triiodo-1,3-benzene Diformamide. Without purification, the next reaction was carried out directly.

Embodiment 3

[0051] Example 3: Preparation of Formula (6) Compound 5-acetamido-3-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-phthalamide

[0052] Reduce the temperature of the viscous compound (5) prepared in Example 2 to 25°C-30°C, slowly add 20% sodium hydroxide solution dropwise under stirring until the reaction liquid is dissolved and adjust the pH value to 13-14, Insulate the reaction for 3 hours, and monitor the complete reaction of the raw materials in the liquid phase. Use concentrated hydrochloric acid to adjust the pH value to neutral, stir at room temperature for 12 hours until a large amount of white solids precipitate, filter the solids out and rinse with water three times, and dry to obtain the hydrolyzate of formula (6) compound 5-acetamido-3-N-(2 ,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide (22g, 62.5% / two-step yield).

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 an iohexol impurity shown in Formula (1) 5-[N-(2, 3-dihydroxy-propyl) acetamido]-3-N-(2, 3-dihydroxy-propyl)-2, 4, 6-triiodo-1, 3-benzenedicarboxamide. Due to synthesis of the iohexol impurity, a reference substance can be provided for qualitative and quantitative analysis of iohexol impurities, the quality standards of iohexol can be improved, andimportant guiding significance can be achieved for safe use of the iohexol.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and more specifically relates to an impurity component 5-[N-(2,3-dihydroxypropyl)acetamido]-3-N-(2, A preparation method of 3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide. Background technique [0002] Iohexol belongs to the second generation of non-ionic monomeric contrast agent, and its trade name is "Omnipaque". It was developed and marketed by Nycomed company in Norway in the early 1980s. In 1982, Omnipaque was first launched in Norway and Sweden. In 1985, it was approved by the US FDA to be launched in the United States. With the rapid development of imaging diagnostic equipment in the world, X-CT contrast agents based on iodine contrast agents have achieved unprecedented development. Iohexol has many advantages such as high safety, high contrast, low osmotic pressure and low human toxicity. It has become the best-selling contrast agent in the international market, and has bec...

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): C07C237/46C07C231/12G01N30/02
Inventor 徐川龙沙琦方钦虎陈骁鹏林勇利王均明陈为飞
Owner ZHEJIANG STARRY PHARMA
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