Method for preparing ioversol

A technology of ioversol and chloroethanol, applied in the field of medicine, can solve problems such as the generation of impurity II that is difficult to avoid, and achieve the effects of improving quality, good process reproducibility and simple operation

Pending Publication Date: 2021-11-30
SHANGHAI ZAIQI BIO TECH
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Chinese patent CN187317 discloses another method for preparing ioversol, which adjusts the order of chlorine hydrolysis on the basis of US5648536, but it is still difficult to avoid the generation of impurity II
[0011] The currently disclosed ioversol preparation methods cannot effectively avoid the generation of impurity II, and the prepared finished product needs to be refined many times to meet the medicinal requirements.

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 ioversol
  • Method for preparing ioversol
  • Method for preparing ioversol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] first step:

[0041] (5-hydroxyacetamide) -N, N'-bis (2,3-dihydroxypropyl) -2,4,6-triiodine-1,3-phenylene terephthalamide (1) (1.0 g 1.31 mmol) and acetone (2.26 mg, 0.013 mmol) were added to acetone (163.78 mg, 1.57 mmol) / acetone (18 mL) solution, and the reaction reflux was heated to 0-5 ° C after cooling to 0-5 ° C. The solution of vinylmethyl ether (83 mg, 1.44 mmol) / acetone (2 mL) was slowly added to the reaction system, and then stirred at room temperature for 18 hours, aqueous sodium hydrogencarbonate solution was washed, dichloromethane extraction, and coated to obtain intermediate 2 ( 0.98g, yield: 84%).

[0042] Step 2:

[0043] Intermediate 2 (0.71 g, 0.79 mmol), chlorocanol (0.126 g, 1.58 mmol) was added with potassium carbonate (0.327 g, 2.37 mmol), and stirred at room temperature for 4 hours, saturated aqueous ammonium chloride solution, Extraction of dichloromethane. The organic layer is coated with intermediate 3 (0.74 g), which is directly used in the n...

Embodiment 2

[0047] first step:

[0048] (5-hydroxyacetamide) -N, N'-bis (2,3-dihydroxypropyl) -2,4,6-triiodine-1,3-phenylenediamide (1) (100g, 131.05 mmol) and ammonium chloride (83.9 mg, 1.57 mmol) were added to a solution of acetone (20.79 g, 157.26 mmol) and tetrahydrofuran (1.8L), and the reaction reflux was heated to 0-5 ° C after cooling to 0-5 ° C. Ethylene ether (11.34 g, 157.26 mmol) / tetrahydrofuran (0.2 L) solution was slowly added to the reaction system, then stirred at room temperature for 18 hours, add aqueous sodium hydrogencarbonate solution, dichloromethane extraction, and dry to dry the intermediate 2 (103.2g, yield: 86%).

[0049] Step 2:

[0050] Intermediate 2 (74.37 g, 81.25 mmol), chlorocyaxethanol (9.81 g, 121.88 mol) were added to N, N-dimethylformamide (1.5 L), and stirred at room temperature 4 at room temperature 4 Hour, saturated aqueous solution of ammonium chloride, extract of dichloromethane. The organic layer is coated with intermediate 3 (78g), which is direc...

Embodiment 3

[0054] first step:

[0055](5-hydroxyacetamide) -N, N'-bis (2,3-dihydroxypropyl) -2,4,6-triiodine-1,3-phenylenediamide (1) (1 kg, 1.31 mol) and acetone (2.71 g, 15.73 mmol) were added to the solution of acetone (252.02 g, 1.57 mol) / dichloromethane (18 L) solution, and the reaction was refluxed for 5 hours and then cooled to 0-5 EtOAc EtOAc EtOAc m. Dry from 0.95 kg of intermediate 2.

[0056] Step 2:

[0057] Intermediate 2 (0.71 kg, 787.78 mmol), chlorocol (63.43 g, 787.78 mmol) was added to potassium t-butoxide (88.9 mmol, 787.78 mmol), and stirred at room temperature for 4 hours, saturated ammonium chloride Aqueous solution, dichloromethane extraction. The organic layer is coated with intermediate 3 (0.74 kg), which is used directly in the next step;

[0058] third step:

[0059] The glacial acetic acid (70.51 g, 1.17 mol) was added to the intermediate 3 (0.74 kg, 0.78 mol) / tetrahydrofuran (3.7 L) solution at 0-5 ° C, stirred at room temperature for 2 hours, the solvent was...

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 a preparation method of a medicine namely ioversol, and belongs to the technical field of medical intermediates. The preparation method comprises the following steps: carrying out acetonylidene protection on (5-hydroxyacetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodine-1,3-benzene dicarboxamide (1) to obtain an intermediate (2), carrying out substitution reaction on the intermediate (2) and chlorohydrin to obtain an intermediate (3), and finally, carrying out acetonylidene removal protection reaction on the intermediate (3) to obtain ioversol. Through protection of different levels, no rearrangement isomer is generated even under a strong alkaline condition, the generation of an impurity II is avoided, the process reproducibility is good, and the method can be smoothly amplified to a kilogram-level reaction scale.

Description

Technical field [0001] The invention belongs to the field of medical technology, and more particularly to the preparation method of listing drug iodineols. Background technique [0002] Iodiol (English Name Ivoersol) is a new type of nonionic contrast agent developed by Mallinkrodt Medicalinc. In 1988, it was approved by the US FDA, which is currently in Japan, UK, France. Listed in China and other areas. After the iodo glycol injection, the X-ray attenuation is reduced due to the high power supply, which can make the vascular imaging of the path clearly. [0003] Iodol is alcoholized to N, N'-double (2,3-dihydroxypropyl) -5- [N- (2-hydroxyethyl) hydroxyacetamin] -2, 4, 6-triiod / 1 , 3-phenylene terephthalamide, chemical structural formula [0004] The preparation method of iodineol is reported more. Many 5-amino-2,4,6-triiodoside is a starting material to prepare an iodine alcohol through the side chain, and the literature report process is adjusted around the method. [0005]...

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): C07C231/12C07C237/46C07D317/28
CPCC07C231/12C07D317/28C07C237/46
Inventor 边奕澄黄成伟熊峰时秋燕魏菱
Owner SHANGHAI ZAIQI BIO TECH
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