Preparation method of X-ray contrast agent ioversol intermediate

A technology of contrast agent and ioversol, applied in the field of organic compound preparation, can solve the problems of increasing the amount of chloroacetyl chloride, increasing production costs and the like, and achieve the effects of shortened reaction steps, low cost and mild reaction conditions

Inactive Publication Date: 2012-06-20
JIANGSU INST OF NUCLEAR MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because there are 4 hydroxyl groups in the molecular structure of 5-amino-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide, they will also React with chloroacetyl chloride to form an ester group. After the reaction, the ester group must be hydrolyzed with alkali, which will greatly increase the amount of chloroacetyl chloride and increase the production cost.

Method used

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  • Preparation method of X-ray contrast agent ioversol intermediate
  • Preparation method of X-ray contrast agent ioversol intermediate
  • Preparation method of X-ray contrast agent ioversol intermediate

Examples

Experimental program
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Effect test

Embodiment 1

[0015] Synthesis of 5-amino-2,4,6-triiodo-1,3-phthaloyl chloride:

Embodiment 2

[0018] Synthesis of 5-chloroacetamido-2,4,6-triiodo-1,3-phthaloyl chloride:

[0019] Dissolve the 5-amino-2,4,6-triiodo-1,3-phthaloyl chloride obtained in the previous step (Example 1) in 125 mL of N,N-dimethylacetamide at room temperature, and stir until uniform Then, cool to 10°C. 16 g (0.15 mol) of chloroacetyl chloride was added dropwise within 30 minutes, then the temperature was raised to 50° C., and the reaction was completed with stirring for 3 hours. After cooling to room temperature, the reaction solution was added dropwise to 300 mL of ice water, during which the temperature was lower than 5 ° C. After stirring for 1 hour, it was filtered, washed with distilled water, and dried to obtain 60 g of the product with a yield of 89% (using 5-amino-2, 4,6-triiodo-1,3-phthalic acid), m.p.>300°C.

Embodiment 3

[0021] Synthesis of 5-chloroacetamido-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide:

[0022] Dissolve 67g (0.1mol) of 5-chloroacetamido-2,4,6-triiodo-1,3-phthaloyl chloride in N,N-dimethylacetamide at room temperature, and cool to below 10°C Finally, 20g (0.2mol) triethylamine and 19g (0.21mol) 3-amino-1,2-propanediol were added, then heated to a reaction temperature of 50°C, stirred for 12 hours to complete the reaction, cooled to below 10°C and filtered. After the filtrate was evaporated under reduced pressure, the residue was dissolved in 60mL (2.5mol / L) sodium hydroxide aqueous solution, and then the pH value was adjusted to 3 with dilute hydrochloric acid, and the precipitated solid was filtered, washed with water, and dried to obtain 71g of the product, which was collected The rate is 91%, m.p.>300°C. 1 H-NMR (DMSO-d 6 , 500MHz) δ (ppm): 3.42 ~ 3.76 (m, 8H), 3.85 (s, 2H), 3.93 ~ 3.96 (m, 2H); MS (FAB) m / z (%): 786 (M + + Na, 100).

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Abstract

The invention discloses a preparation method of X-ray contrast agent ioversol intermediate, belonging to the technical field of organic compound preparation. The chemical name of the intermediate is 5-chloroacetamide-N,N'-bi(2,3-dyhydroxyl propyl)-2,4,6-triiodo-1,3-benzenedicarboxamide. The method utilizes 5-amino-2,4,6-triiodo-1,3-phthalic acid to react with thionyl chloride, and then reacts with chloroacetic chloride to obtain 5-chloroacetamide-2,4,6-triiodo-1,3-benzenedicarbonyl dichloride, finally reacts with 3- amino-1,2- propylene glycol to obtain the 5-chloroacetamide-N,N'-bi(2,3-dyhydroxyl propyl)-2,4,6-triiodo-1,3-benzenedicarboxamide. The method has simple synthesis process route, shortened reaction steps, mild reaction condition, security and reliability, stable quality, high yield, low cost and less equipment investment, thereby being applicable to large-scale industrial production.

Description

technical field [0001] The invention discloses a preparation method of a non-ionic X-ray contrast agent ioversol intermediate, which belongs to the technical field of organic compound preparation. Background technique [0002] In 1982, the U.S. Wanlingke Company successfully developed the non-ionic X-ray contrast agent Ioversol (Ioversol, the product name is Ansheli, Optiray), and the chemical name is N, N'-bis(2,3-dihydroxypropane). base)-5-[N-(2-hydroxyethyl)-glycolamido]-2,4,6-triiodo-1,3-benzenedicarboxamide. Ioversol has good water solubility, low osmotic pressure, relatively stable chemical properties, and can withstand high temperature sterilization. It can be made into an injection solution for the market, and can be widely used in intravascular applications, subarachnoid applications, and body cavities. application and gastrointestinal examination, etc. 5-Chloroacetamido-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide is the key intermediate ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C237/46C07C231/02
Inventor 邹霈罗世能谢敏浩刘娅灵何拥军王洪勇吴军
Owner JIANGSU INST OF NUCLEAR MEDICINE
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