Method for preparing calcobutrol

A production method and the technology of butol, which are applied in the field of producing high-purity calcobutrol

Pending Publication Date: 2021-08-17
东国生命科学株式会社
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] However, the above method also has a disadvantage that in order to synthesize high-purity butanol

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 calcobutrol
  • Method for preparing calcobutrol
  • Method for preparing calcobutrol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Crude Butanol (2,2',2"-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10) - Production of tetraazacyclododecane-1,4,7-triyl)triacetic acid)

[0050] Dissolve 100 grams of rotenin (1,4,7,10-tetraazacyclododecane) in 500 milliliters of purified water and heat to a temperature of 40-45° C., slowly drop 84 grams of 4,4-Dimethyl-3,5,8-trioxabicyclo[5,1,0]octane. After reacting for 24 hours, 408 ml of hydrochloric acid was added dropwise to the reaction solution, followed by stirring at 75°C for 2 hours. The reaction solution was concentrated in vacuo, and 500 ml of ethanol was added thereto. The resulting solution was stirred and cooled at reflux, and the crystals formed were filtered.

[0051] The formed crystals were dissolved in 500 ml of purified water, and 170 g of chloroacetic acid was added thereto. The pH of the resulting solution was adjusted to 9-10 using 45% sodium hydroxide (NaOH), heated to 70°C, and stirred for 12 hours while maintaining the pH...

Embodiment 2

[0055] Example 2: Butanol (2,2',2"-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazole Purification of heterocyclododecane-1,4,7-triyl)triacetic acid)

[0056] Concentrated butanol was dissolved in 500 ml of purified water and passed through a column containing a mixture of 100 ml of anion (IRA-67) and 100 ml of cation (IR-120). The passing butanol eluate was recycled to the column containing the mixture, and this operation was repeated several times. Wash the resin, combine the eluent and washing solution, adjust the pH value to 3.5-4.5 with cations, filter, and then concentrate. 100 ml of purified water was added to the concentrated solution, and after it was completely dissolved, it was heated to 80° C., and then 500 ml of methanol was added thereto. The resulting solution was cooled slowly to room temperature, and a small amount of seed crystals were added thereto. After stirring for 2 days, the crystals formed were filtered. The crystals were vacuum-dried ...

Embodiment 3

[0062] Embodiment 3: the production of calbutril calcium

[0063] 10 g of high-purity butanol (purity: 99.5% or higher) produced in Example 2 was dissolved in 100 ml of purified water, and 2.22 g of calcium carbonate (CaCO 3 ). The mixture was stirred at room temperature for 1 hour, filtered through a 0.2 micron filter, concentrated, and then freeze-dried to obtain 10.7 g of Calcobutrol (yield: 99%, purity: 99.5% or higher).

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 present invention relates to a preparation method for synthesizing highly pure calcobutrol without using highly pure gadobutrol, via the preparation of highly pure butrol through a purification step of butrol which is an intermediate of gadobutrol synthesis.

Description

technical field [0001] The invention relates to a method for producing high-purity butrol with a purity greater than 99% through an efficient purification process of low-purity butrol and using the high-purity butrol to produce high-purity calcobutrol. Background technique [0002] Gadobutrol is a gadolinium-containing contrast agent used in nuclear spin tomography. In the field of gadolinium-containing magnetic resonance imaging (MRI) contrast agents, gadobutrol is sold globally under the trade names Gadovist or Gadavist. [0003] It has been found that for most gadolinium-containing contrast agents it is advantageous to employ an excess of the complex-forming ligand in the formulation in the form of the calcium complex. The role of the calcium complex is to prevent the release of free gadolinium from the formulation (eg, recomplexation with foreign ions in glass vials through storage for several years). [0004] That is, calcobutrol in Gadovist is an additive in gadobutr...

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): C07D257/02
CPCC07D257/02
Inventor 权赫哲金京俊文宝贤林大圣
Owner 东国生命科学株式会社
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