Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Manufacture of a triiodinated contrast agent

A technology of contrast agent and iodination, which is applied in the production field of tri-iodinated contrast agent, can solve problems such as being unfavorable to the environment, uneconomical and the like, and achieve the effect of high purity

Inactive Publication Date: 2017-12-08
霍维奥恩联合有限公司
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These methods generate large amounts of by-products, making them atomically less economical and less environmentally friendly

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
  • Manufacture of a triiodinated contrast agent
  • Manufacture of a triiodinated contrast agent
  • Manufacture of a triiodinated contrast agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Preparation of (S)-5-(2-acetoxypropionylamino)-2,4,6-triiodoisophthalic acid

[0051] To a solution of 5-amino-2,4,6-triiodoisophthalic acid (1.0 g, 1.79 mmol) in DMA (5 ml) was added dropwise (S)-1-chloro-1-oxopropane-2- Glycolacetate (0.75ml, 5.91mmol). The resulting mixture was stirred at about 50°C for 5 hours and 20 minutes. 80 ml of water are added to the reaction mixture at room temperature, after which the resulting suspension is cooled to a temperature between 0° C. and 5° C. and stirred at this temperature for 25 minutes. The suspension was filtered and the solid was washed with water. The product was dried in a vacuum oven at 40°C to obtain (S)-5-(2-acetoxypropionylamino)-2,4,6-triiodoisophthalic acid (0.695g, 1.03mmol). MS, 1 H-NMR and 13 C-NMR data is consistent with the structure of (S)-5-(2-acetoxypropionylamino)-2,4,6-triiodoisophthalic acid.

[0052] Yield: 57.5%

[0053] HPLC purity: 99.91%

[0054] (Chromatographic column: μPorasil 125A 10 μm ...

Embodiment 2

[0058] Preparation of (S)-5-(2-acetoxypropionylamino)-2,4,6-triiodoisophthalic acid

[0059] To a suspension of 5-amino-2,4,6-triiodoisophthalic acid (50.0 g, 89.5 mmol) in DMA (100 ml) was slowly added (S)-1 at a temperature between 25 °C and 29 °C -Chloro-1-oxopropan-2-yl acetate (37.4ml, 295.4mmol). The resulting mixture was heated to about 50°C and stirred at this temperature for about 8 hours, after which time the heat was removed and the mixture was stirred at room temperature for about 14 hours. The reaction mixture was slowly added to water (500ml) at a temperature between 22°C and 30°C with vigorous stirring. After the addition, 300 ml of water were added to the suspension. The suspension was stirred for a further 5 hours at about 22°C, after which the white solid was filtered off and washed twice (30 ml each) with water previously cooled at about 5°C. The product was dried in a vacuum oven at about 50°C to obtain (S)-5-(2-acetoxypropionylamino)-2,4,6-triiodoisopht...

Embodiment 3

[0065] Preparation of (S)-1-((3,5-bis(chlorocarbonyl)-2,4,6-triiodophenyl)amino)-1-oxopropan-2-yl acetate

[0066] Phosphorus pentachloride (37.1g, 178.3mmol) was added in batches to (S)-5-(2-acetoxypropionylamino)-2,4,6-triiodoisophthalic acid obtained in Example 2 Formic acid (40.0 g, 59.4 mmol) in DMA (200 ml). The reaction mixture was stirred at about 40°C for 6 hours, after which it was added dropwise over 1 hour to water (400 ml) cooled to a temperature between 0°C and 5°C with vigorous stirring. The resulting suspension was stirred for a further hour at a temperature between 0°C and 5°C and the white precipitate was filtered off. The white solid was washed with water (80ml) previously cooled to a temperature between 0°C and 5°C. The solid was resuspended in a mixture of water (103ml) and isopropanol (80ml) and stirred at this temperature for 15 minutes. The suspension was warmed to a temperature between 20°C and 25°C and stirred at this temperature for 30 minutes, th...

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

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to manufacture of a triiodinated contrast agent. The invention further relates to a new compound, (S)-5-(2-acetoxypropanamido)-2,4,6-triiodoisophthalic acid, of formula II (S)-5-(2-acetoxypropanamido)-2,4,6-triiodoisophthalic acid. Said new compound is of use for the production of triiodinated contrast agent, especially lopamidol, with low content of acetyl and hydroxyacetyl analogs. The new compound may be formed from 5-amino-2,4,6-triiodoisophtalic acid by acylating with (S)-1-chloro-1-oxopropan-2-yl acetate. The new compound may then be converted to the respective acid dichloride by reacting with a chlorinating reagent, which is a further object of the present invention, followed by the amidation with 2-amino-1,3-propanediol and acetate hydrolysis.

Description

[0001] This application is a divisional application of the application dated February 2, 2012, the application number is 201280041065.X, and the invention name is "production of tri-iodinated contrast medium". technical field [0002] The present invention relates to the field of production of triiodinated contrast agents. The present invention relates to a process for the production of triiodinated contrast agents such as iopamidol via novel chemical compounds. Background technique [0003] Iopamidol is one of the most commonly used nonionic iodinated X-ray contrast agents. A multi-step synthesis is involved in the production of iopamidol. [0004] Several methods for the synthesis of iopamidol have been published in the literature. The process originally described for the preparation of iopamidol, as disclosed in GB1472050 and US4001323, by reacting 5-amino-2,4,6-triiodoisophthaloyl dichloride with (S)-1-chloro -1-Oxopropan-2-yl acetate reacts to introduce a chiral cent...

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): C07C235/16C07C231/12C07C231/02
CPCC07C231/02C07C231/12C07C235/16C07C231/18C07C237/46C07C231/24
Inventor J·M·加林德罗阿纳·克里斯蒂安·克鲁斯J·J·班达拉W·赫吉
Owner 霍维奥恩联合有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com