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

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

Uses

Used in Medical Imaging:
Iomeprol is used as a radiopaque medium for various diagnostic imaging procedures, such as X-ray computed tomography (CT) and angiography. It enhances the visibility of blood vessels and internal organs by increasing the contrast between different tissues, allowing for more accurate diagnosis and assessment of various conditions.
Used in Pharmaceutical Industry:
Iomeprol is also used in the pharmaceutical industry as an active pharmaceutical ingredient (API) for the development of contrast agents. These agents are essential for improving the quality and accuracy of medical imaging, which is crucial for early detection and treatment of various diseases and conditions.

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

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

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

A manufacturing method of the present invention reduces treatment processes when manufacturing a contrast medium or an intermediate thereof, and thus generates less waste solvent, thereby being eco-friendly and capable of significantly reducing a manufacturing cost. Therefore, the manufacturing method of the present invention is economical and suitable for mass production since the production cost of the contrast medium can be greatly reduced.

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)

PROCESS FOR THE PROPARATION OF CONTRAST MEDIUM IOMEPROL

The present invention relates to a method for preparing an X-ray contrast agent iomeprol and, more specifically, to a method for preparing iomeprol by adding an inorganic base, an inorganic chloride, a solvent, etc. to 5-(2-hydroxyacetamido)-N,Nandprime;-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (1b) to induce N-methylation reaction, thereby enabling easy separation and removal of inorganic salts generated during the reaction, without treatment with an ion exchange resin, while reducing the conventional production time, and minimization of the amount of reaction impurities.COPYRIGHT KIPO 2020

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

NOVEL INTERMEDIATE COMPOUND AND PREPARATION PROCESS OF IOMEPROL USING THEREOF

The present invention relates to a novel intermediate compound of iomeprol, a production method thereof, and a method for producing iomeprol using the same. More specifically, the present invention relates to a method for producing iomeprol used as X-ray vascular contrast agents in an economically feasible way with high purity using a novel intermediate N,Nandprime;-bis(2,3-diacetylatepropyl)-5-(2-acetoxy-N-methylacetoamide)-2,4,6-triiodoisophthalamide. The present invention further relates to a purification method thereof.COPYRIGHT KIPO 2017

Novel method for preparing iomeprol

The invention belongs to the technical field of non-ionic X-ray contrast agents, and discloses a novel method for preparing iomeprol. The preparation method comprises the steps of carrying out N-methylation reaction by employing a compound 5-aminoisophthalic acid as a raw material; carrying out esterification reaction; carrying out amidation reaction; carrying out iodination reaction; carrying out chloroacetylation reaction; and finally carrying out hydroxylation reaction to prepare the iomeprol. The preparation method is stable in quality, high in yield, low in cost, environmentally friendly, and easy for realization of industrial mass production.

A PROCESS FOR THE RECOVERY OF IODINE FROM AQUEOUS SOLUTIONS CONTAINING IODINATED ORGANIC COMPOUNDS

A process for the recovery of iodine from mother liquors or wastes containing iodinated organic compounds, by mineralisation of organic iodine and subsequent transformation of the formed iodide into elementary iodine, characterized in that the aqueous solution is concentrated to a suitable volume before the mineralisation step, under atmospheric pressure and at the boiling temperature, and said solution is purified by nanofiltration.

Smiles rearrangement as a tool for the preparation of 5-[(2-hydroxyacyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamides: Main pathway and side reactions

In the preparation of 5-[(2-hydroxyacyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxamides 1a-h from 2a-h two conditions using stoichiometric amounts of base (method A - aq NaOH at 50°C; method B - MeONa in DMF at r, t.) were used. Yields are good to excellent provided that the right conditions are chosen. Primary amides 2a,b give 1a,b with method B only, whereas with method A extensive hydrolysis of the CONH2 moiety is observed. N-Methyl derivatives 2c,d afford 1c,d with either method. However, with method B long reaction times lead to the formation of large amounts of benzoxazinones, 4c,d. Under the same conditions, the pattern of side products which are formed from N-(hydroxyalkyl)phenoxyacetamides 2e-g is further complicated by: i) intramolecular cyclizations leading to bicyclic (7f,g) and tricyclic structures (5) ii) N-deacylation; iii) double Smiles rearrangement reactions.