92339-11-2

Usage

InChI:InChI=1/C35H44I6N6O15/c1-13(52)46(30-26(38)20(32(59)42-3-15(54)9-48)24(36)21(27(30)39)33(60)43-4-16(55)10-49)7-19(58)8-47(14(2)53)31-28(40)22(34(61)44-5-17(56)11-50)25(37)23(29(31)41)35(62)45-6-18(57)12-51/h15-19,48-51,54-58H,3-12H2,1-2H3,(H,42,59)(H,43,60)(H,44,61)(H,45,62)

Upstream product

• 31127-80-7 N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide 
• 106-89-8 epichlorohydrin 
• 96-23-1 1,3-Dichloro-2-propanol 
• 28659-12-3 1,3-dichloro-2-(6-(3,4,5,6-tetrahydro-2H-pyranoxy))propane 
• 616-30-8 3-Amino-1,2-propanediol 
• 13290-96-5 dimethyl 5-nitroisophthalate 
• 76820-34-3 5-nitro-N,N'-bis-(2,3-dihydroxypropyl)isophthalamide 
• 76820-35-4 5-Amino-N,N'-bis[2,3-dihydroxypropyl]-1,3-benzenedicarboxamide 

Relevant academic research and scientific papers

An intermediate of iodoxanol and a method for preparing iodixanol thereof

The present invention provides a method for preparing iodoxasol intermediates of iodoxaol, the intermediate formula VI of iodkesarol VI: 5,5'-[(2-hydroxy-1,3-propanedioxy)bis (acetylimino)] bis [N,N'-bis(2,3-dihydroxypropyl)-1,3-benzenedicarboxamide], iodized by formula VI to obtain iodoxaol finished products; the present invention provides a new synthetic idea of first forming a dimer and then iodizing, The prepared iodoxaol finished product: the total impurity content ≤ 1.0%, the impurity G content ≤0.5%; the method of the present invention has mild reaction conditions, low damage to the equipment, simple process, green environmental protection and low cost, can ensure the continuous production of high-quality products, has a high application value, suitable for industrial production.

Preparation method of iodixanol

The invention provides a preparation method of iodixanol, which comprises the following steps: (1) reacting 5-amino-2,4,6-triiodoisophthalate (I) with acetic anhydride to obtain 5-acetamido-2,4,6-triiodoisophthalate (II), and reacting the 5-acetamido-2,4,6-triiodoisophthalate (II) with acetic anhydride to obtain iodoxanol (II); (2) reacting the 5-acetamido-2,4,6-triiodoisophthalate (II) with 1,3-dichloro-2-propanol (or 1,3-dibromo-2-propanol and epichlorohydrin) to generate 5,5'-((2-hydroxypropane-1,3-diyl)bis(acetamido))bis(2,4,6-triiodoisophthalate ethyl ester); and (3) carrying out ammonolysis reaction on the 5,5'-((2-hydroxypropane-1,3-diyl)bis(acetamido))bis(2,4,6-triiodoisophthalate ethyl ester) and 1-amino-2,3-propylene glycol to obtain the iodixanol (IV). The purity of the crude iodixanol product is greater than 95%, the highest content of single impurity is lower than 1.5%, and the content of other single impurities in the product is lower than 1%, so that the difficulty of purifying the product is reduced, the requirement on production equipment is reduced, and the method is suitable for large-scale production and is beneficial to improving the industrial production efficiency.

Iodixanol and synthesis method thereof

The invention belongs to the technical field of macromolecules, and discloses iodixanol and a synthesis method thereof. With a compound 5-acetamido-N, N'-bis(2, 3-dihydroxypropyl)-2, 4, 6-triiodo-isophthalamide as a raw material, an intermediate compound 5-acetamido-N, N'-bis(2, 3-dimethyl-1, 3-dioxolan-4-yl)methyl)-2, 4, 6-triiodo-isophthalamide is produced through addition of acetic acid and concentrated sulfuric acid. In allusion to the defects of the existing methods for preparing the iodixanol, through production of the novel intermediate compound, production of difficultly removed O-alkylated impurities during a reaction is avoided. The invention provides a method for synthesizing the iodixanol, which is more reasonable, higher in yield and higher in purity. By the method, the reaction cost is lower.

DESALINATION OF A COMPOSITION COMPRISING A CONTRAST AGENT

The invention relates to industrial preparation of contrast agents, and further to an improved process for the purification of contrast agents. In particular, it relates to a process for reducing the salt content of compositions comprising an MR contrast agent or an X-ray contrast agent, such as a non-ionic iodinated monomeric compound or a non-ionic iodinated dimeric compound.

DESALINATION OF A COMPOSITION COMPRISING A CONTRAST AGENT

The invention relates to industrial preparation of contrast agents, and further to an improved process for the purification of contrast agents. In particular, it relates to a process for reducing the salt content of compositions comprising an MR contrast agent or an X-ray contrast agent, such as a non-ionic iodinated monomeric compound or a non-ionic iodinated dimeric compound.

Preparation and Purification of Iodixanol

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%.

SYTNHESIS OF IODIXANOL IN METHANOL

This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N′-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with methanol as solvent.

PREPARATION AND PURIFICATION OF IODIXANOL

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%.

Synthesis of iodixanol in 1-methoxy-2-propanol and water or methanol

This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with a solvent mixture comprising 1-methoxy-2-propanol and water or methanol.

Synthesis of iodixanol in methanol

This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with methanol as solvent.