78649-41-9

Basic information

• Product Name: IOMEPROL
• Synonyms: IOMEPROL;1,3-Benzenedicarboxamide, N,N'-bis(2,3-dihydroxypropyl)-5-[(hydroxyacetyl)methylamino]-2,4,6-triiodo-;Imeron;Iomeron 350;Iomeron;N,N'-bis(2,3-dihydroxypropyl)-5-[(hydroxyacetyl)methylamino]-2,4,6-triiodo-1,3-benzenedicarboxamide;N,N'-Bis(2,3-dihydroxypropyl)-5-[methyl(hydroxyacetyl)amino]-2,4,6-triiodoisophthalamide;N,N'-bis(2,3-dihydroxypropyl)-5-[(hydroxyacetyl)MethylaMino]-2,4,6-triiodo -
• CAS NO: 78649-41-9
• Molecular Formula: C₁₇H₂₂I₃N₃O₈
• Molecular Weight: 777.09
• EINECS: 1533716-785-6
• Product Categories: pharmacetical;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 78649-41-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 263-265?C
• Boiling Point: 813.185 °C at 760 mmHg
• Flash Point: 445.599 °C
• Appearance: White Solid
• Density: d420 1.166; d437 1.161; d420 1.334; d437 1.329; d420 1.446; d437
• Vapor Pressure: 5.95E-28mmHg at 25°C
• Refractive Index: nD20 1.3828; nD20 1.4327; nD20 1.4660
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 11.36±0.46(Predicted)
• CAS DataBase Reference: IOMEPROL(CAS DataBase Reference)
• NIST Chemistry Reference: IOMEPROL(78649-41-9)
• EPA Substance Registry System: IOMEPROL(78649-41-9)

Safety Data

• Hazardous Substances Data: 78649-41-9(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Diagnostic aid (radiopaque medium).

Definition

ChEBI: A benzenedicarboxamide compound having N-substituted carbamoyl groups at the 1- and 3-positions, iodo substituents at the 2-, 4- and 6-positions and a glycoloyl(methyl)amino group at the 5-position.

InChI:InChI=1/C17H22I3N3O8/c1-23(9(29)6-26)15-13(19)10(16(30)21-2-7(27)4-24)12(18)11(14(15)20)17(31)22-3-8(28)5-25/h7-8,24-28H,2-6H2,1H3,(H,21,30)(H,22,31)

Synthetic route

N1,N3-bis(2,3-dihydroxypropyl)-5-(2-hydroxyacetamido)-2,4,6-triiodobenzene-1,3-dicarboxamide (77868-40-7) + methyl iodide (74-88-4) → iomeprol (78649-41-9)

Conditions	Yield
With sodium hydroxide In N,N-dimethyl acetamide at 10 - 60℃; for 16h;	95%
With sodium hydroxide In N,N-dimethyl acetamide at 10 - 60℃;	95%

2-((3,5-bis((2,3-dihydroxypropyl)carbamoyl)-2,4,6-triiodophenyl)(methyl)amino)-2-oxoethylacetate → iomeprol (78649-41-9)

Conditions	Yield
With sodium hydroxide In water at 20℃; for 3h; Reagent/catalyst; Temperature;	90%
Multi-step reaction with 2 steps 1: pyridine / 20.5 h / 5 - 20 °C 2: calcium hydroxide / water / 4 h / 20 °C View Scheme

5-[N-methyl-2-chloroacetamido]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide → iomeprol (78649-41-9)

Conditions	Yield
With sodium acetate In water for 17h; Time; Reflux; Large scale;	88%

3-(3-((2-acetoxy-3-acetoxypropyl)carbamoyl)-5-(2-acetoxy-N-methylacetamido)-2,4,6-triiodobenzamido)propane-1,2-diyl diacetate → iomeprol (78649-41-9)

Conditions	Yield
With calcium hydroxide In water at 20℃; for 4h; Reagent/catalyst; Temperature;	84%
With sulfuric acid In methanol for 3h; Solvent; Reflux;	65%

N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodo-5-methylcarbamoylmethoxy-isophthalamide → iomeprol (78649-41-9)

Conditions	Yield
With sodium hydroxide In water at 50℃; Smiles rearrangement;	81%

5-aminoisophthalic acid (99-31-0) → iomeprol (78649-41-9)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: sulfuric acid / chloroform / 7 h / 50 - 60 °C / Large scale 2.1: sulfuric acid / 9 h / Reflux; Large scale 3.1: sodium methylate / methanol / 12 h / 5 °C / Reflux 4.1: Iodine monochloride / water / 5 h / 64 - 90 °C / Large scale 4.2: 36 h / 5 - 50 °C / pH 2 / Large scale 5.1: N,N-dimethyl acetamide / 2 h / 10 - 70 °C / Large scale 5.2: 4 h / 30 - 50 °C / Large scale 6.1: sodium acetate / water / 17 h / Reflux; Large scale View Scheme

5-methylaminoisophthalic acid → iomeprol (78649-41-9)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sulfuric acid / 9 h / Reflux; Large scale 2.1: sodium methylate / methanol / 12 h / 5 °C / Reflux 3.1: Iodine monochloride / water / 5 h / 64 - 90 °C / Large scale 3.2: 36 h / 5 - 50 °C / pH 2 / Large scale 4.1: N,N-dimethyl acetamide / 2 h / 10 - 70 °C / Large scale 4.2: 4 h / 30 - 50 °C / Large scale 5.1: sodium acetate / water / 17 h / Reflux; Large scale View Scheme

5-methylaminoisophthalic acid dimethyl ester (55648-31-2) → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium methylate / methanol / 12 h / 5 °C / Reflux 2.1: Iodine monochloride / water / 5 h / 64 - 90 °C / Large scale 2.2: 36 h / 5 - 50 °C / pH 2 / Large scale 3.1: N,N-dimethyl acetamide / 2 h / 10 - 70 °C / Large scale 3.2: 4 h / 30 - 50 °C / Large scale 4.1: sodium acetate / water / 17 h / Reflux; Large scale View Scheme

5-methylamino-N, N'-bis(2,3-dihydroxypropyl)-1,3-benzenedicarboxamide → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: Iodine monochloride / water / 5 h / 64 - 90 °C / Large scale 1.2: 36 h / 5 - 50 °C / pH 2 / Large scale 2.1: N,N-dimethyl acetamide / 2 h / 10 - 70 °C / Large scale 2.2: 4 h / 30 - 50 °C / Large scale 3.1: sodium acetate / water / 17 h / Reflux; Large scale View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: dmap / ethyl acetate / 2 h / Reflux 2: N,N-dimethyl-formamide / 4 h / 40 °C 3: potassium carbonate / acetone / 12 h / -5 - 20 °C 4: sulfuric acid / methanol / 3 h / Reflux View Scheme
Multi-step reaction with 4 steps 1: dmap / ethyl acetate / 2 h / Reflux 2: N,N-dimethyl-formamide / 4 h / 40 °C 3: potassium carbonate / acetone / 5 h / 20 °C 4: sulfuric acid / methanol / 3 h / Reflux View Scheme

5-amino-N,N'-bis[2,3-bis(acetyloxy)propyl]2,4,6-triiodo-1,3-benzenedicarboxamide (76801-94-0) → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 4 h / 40 °C 2: potassium carbonate / acetone / 12 h / -5 - 20 °C 3: sulfuric acid / methanol / 3 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 4 h / 40 °C 2: potassium carbonate / acetone / 5 h / 20 °C 3: sulfuric acid / methanol / 3 h / Reflux View Scheme

5-(acetoxyacetylamino)-N,N'-bis(2,3-diacetoxypropyl)-2,4,6-triiodoisophthalamide → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / 12 h / -5 - 20 °C 2: sulfuric acid / methanol / 3 h / Reflux View Scheme

N1,N3-bis(2,3-dihydroxypropyl)-5-(2-hydroxyacetamido)-2,4,6-triiodobenzene-1,3-dicarboxamide (77868-40-7) + dimethyl sulfate (77-78-1) → iomeprol (78649-41-9)

Conditions	Yield
Stage #1: N,N'-bis-(2,3-dihydroxypropyl)-5-(2-hydroxyacetylamino)-2,4,6-triiodoisophthalamide With calcium chloride In methanol at 70℃; for 3h; Stage #2: With calcium hydroxide In methanol at 0 - 5℃; for 1h; Stage #3: dimethyl sulfate In methanol at 0 - 5℃; for 7h; Temperature;	4.21 g

2-((3,5-bis (chlorocarbonyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate (78314-12-2) → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl acetamide / 15 h / 15 - 30 °C 2: sodium hydroxide / water / 8 h / 25 - 30 °C 3: sodium hydroxide / N,N-dimethyl acetamide / 16 h / 10 - 60 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl acetamide / 15 h / 15 - 30 °C 2: water; sodium hydroxide / 8 h / 25 - 30 °C 3: sodium hydroxide / N,N-dimethyl acetamide / 10 - 60 °C View Scheme

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: N,N-dimethyl acetamide / 20.5 h / 20 - 25 °C 2: triethylamine / N,N-dimethyl acetamide / 15 h / 15 - 30 °C 3: sodium hydroxide / water / 8 h / 25 - 30 °C 4: sodium hydroxide / N,N-dimethyl acetamide / 16 h / 10 - 60 °C View Scheme
Multi-step reaction with 4 steps 1: N,N-dimethyl acetamide / 2.5 h / 20 - 25 °C 2: triethylamine / N,N-dimethyl acetamide / 15 h / 15 - 30 °C 3: water; sodium hydroxide / 8 h / 25 - 30 °C 4: sodium hydroxide / N,N-dimethyl acetamide / 10 - 60 °C View Scheme

2-((3,5-bis((2,3-dihydroxypropyl)carbamoyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate → iomeprol (78649-41-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / water / 8 h / 25 - 30 °C 2: sodium hydroxide / N,N-dimethyl acetamide / 16 h / 10 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: water; sodium hydroxide / 8 h / 25 - 30 °C 2: sodium hydroxide / N,N-dimethyl acetamide / 10 - 60 °C View Scheme

Upstream product

• 155887-14-2 N,N'-bis[2,3-di(2-chloroacetoxy)propyl]-5-(2-chloroacetamido)-2,4,6-triiodoisophthalamide 
• 37441-29-5 5-amino-2,4,6-triiodoisophthalic acid dichloride 
• 78314-12-2 2-((3,5-bis (chlorocarbonyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate 
• 77868-40-7 N₁,N₃-bis(2,3-dihydroxypropyl)-5-(2-hydroxyacetamido)-2,4,6-triiodobenzene-1,3-dicarboxamide 
• 74-88-4 methyl iodide 
• 77-78-1 dimethyl sulfate 
• 87785-51-1 5-(acetoxyacetylamino)-N,N'-bis(2,3-diacetoxypropyl)-2,4,6-triiodoisophthalamide 
• 76801-94-0 5-amino-N,N'-bis[2,3-bis(acetyloxy)propyl]2,4,6-triiodo-1,3-benzenedicarboxamide 
• 76801-93-9 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 
• 55648-31-2 5-methylaminoisophthalic acid dimethyl ester 
• 99-31-0 5-aminoisophthalic acid 

Relevant articles and documents

Synthesis method of iomeprol

The invention relates to a preparation method of iomeprol. The iomeprol is a non-ionic X-ray contrast agent with excellent safety and contrast effect. The invention relates to a synthesis method of iomeprol, which is characterized in that 5-amino-N, N '-bis (2, 3-dihydroxy propyl)-2, 4, 6-triiodo-1, 3-benzene dicarboxamide (compound II) is used as an initial raw material, chloroacetylation, methylation, hydrolysis and hydroxylation reactions are sequentially carried out to synthesize an iomeprol product, and the synthesis route is as follows. The chemical method for preparing iomeprol is realized through the following steps: acylation reaction, methylation reaction, hydrolysis reaction and hydroxylation reaction. The preparation method disclosed by the invention is stable in quality, high in yield, low in cost, small in pollution and easy to realize industrial production.

New Methods for Preparing an Intermediate of Contrast Medium and Methods for Preparing Contrast Medium

The present invention relates to a method for preparing an intermediate of contrast agent or contrast agent. Also, the manufacturing cost can be significantly reduced. , The manufacturing method of the present invention can greatly reduce the production cost of contrast agents and is suitable for mass production. (by machine translation)

preparation method of contrast agent

The present invention relates to a method for producing a contrast medium with high purity and high efficiency, and since no methyl iodide and the like are used in a production process, no salt is generated or only a very small amount thereof is generated, and a high purity and high efficiency contrast medium can be produced without complicated purification and washing steps. In addition, a small amount of salt can be easily removed by washing with water.COPYRIGHT KIPO 2018