Preparation and purification of iodixanol

Abstract

An improved synthesis method for preparation of iodixanol, and a purification process through macroporous adsorption resin chromatographic column and recrystallization are provided. The synthesis method relates to dimerization of 5-acetamido-N, N'-bis(2,3-dihydroxypropyl)-2,4,6- triiodo-isophthalamide (compound A) to prepare iodixanol, wherein excessive side reactions such as alkylation are effectively inhibited by controlling the pH of the reaction mixture with a boron-containing acidic substance or salts thereof such as boric acid. In this way, the conversion rate of compound A to iodixanol is 85-90%. The iodixanol crude product is purified by a macroporous adsorption resin chromatographic column, obtaining iodixanol product with recovery of 90-95% and purity of 96-98%. The iodixanol crude product is recrystallized in mixed solvent containing 2-methoxyethanol, obtaining iodixanol product with recovery of 90-95% and purity of greater than 99%.

Description

technical field

[0001] The invention belongs to the field of chemical medicine and relates to iodixanol (1,3-bis(acetylamino)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2 , 4,6-triiodo-phenyl]-2-hydroxypropane) preparation and purification method. Background technique

[0002] Iodixanol, brand name Developed by Nycomed as a non-ionic X-ray contrast agent. Iodixanol was introduced in 1993 and is produced in large quantities.

[0003] The production of this non-ionic X-ray contrast agent includes chemical manufacturing (primary production (primary production)) and pharmaceutical preparation manufacturing (secondary production (secondary production)); iodixanol The primary production of methionin involves multi-step chemical synthesis and is completed by a purification process.

[0004] Iodixanol for injection is injected directly into human blood vessels in very high doses, which means that the iodixanol used as raw material in secondary production needs to be of ...

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