37441-29-5

Usage

Chemical Properties

Yellow Solid

Uses

5-Amino-2,4,6- triiodisophthaloyl acid dichloride is used in the preparation of trimeric X-ray contrast agents.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C8H2Cl2I3NO2/c9-7(15)1-3(11)2(8(10)16)5(13)6(14)4(1)12/h14H2

Synthetic route

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
With pyridine; thionyl chloride In 1,2-dichloro-ethane at 70 - 85℃; for 8.5h;	100%
With pyridine; thionyl chloride In 1,2-dichloro-ethane at 70 - 85℃; for 7.5 - 8h;	100%
With pyridine; thionyl chloride In 1,2-dichloro-ethane at 70 - 85℃; for 7.5 - 8h;	100%

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + 2-chloro-1,3-dimethylimidazolinium chloride (37091-73-9) → 5-amino-2,4,6-triodoisophthaloyl dichloride + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
In hexane; toluene	A 95% B n/a

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + 2-chloro-1,3-dimethylimidazolinium chloride (37091-73-9) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
	93%

5-sulfinylamino-2,4,6-triiodoisophthalic acid chloride → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
With water In acetone for 26h;	85.5%

5-aminoisophthalic acid (99-31-0) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 73 percent / ICl; KCl / H2O / 24 h / 55 °C 2: 89.3 percent / SOCl2 / 6 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 74 percent / aq. potassium iododichloride / H2O / 18 h / 55 - 60 °C 2: 92 percent / thionyl chloride View Scheme

5-nitrobenzene-1,3-dicarboxylic acid (618-88-2) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Iodine monochloride / 5 h / 70 °C / Inert atmosphere 2.1: phosphorus pentachloride / 0.67 h / 30 °C 2.2: 0.17 h View Scheme

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) + Acetoxyacetyl chloride (13831-31-7) → 2-((3,5-bis (chlorocarbonyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate (78314-12-2)

Conditions	Yield
In water	99%
In N,N-dimethyl acetamide at 20℃; for 15h; Cooling;	92%
In tetrahydrofuran; n-heptane at 20℃; Product distribution / selectivity; Heating / reflux;	35%

acetyl chloride (75-36-5) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5)

Conditions	Yield
In water	99%
In ISOPROPYLAMIDE at 0℃; for 12h;	81%
In N,N-dimethyl acetamide at 0 - 20℃; for 4h;	50%
In N,N-dimethyl acetamide at 20℃; Inert atmosphere; Cooling with ice;

acetic anhydride (108-24-7) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5)

Conditions	Yield
sulfuric acid In acetonitrile Product distribution / selectivity;	97%
sulfuric acid for 1h; Product distribution / selectivity;	76%

TFA-Gly (383-70-0) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride (752253-20-6)

Conditions	Yield
Stage #1: TFA-Gly With thionyl chloride In ISOPROPYLAMIDE at 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride In ISOPROPYLAMIDE at 0 - 20℃; for 96h;	97%

glycinium trifluoroacetate (677-30-5) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride (752253-20-6)

Conditions	Yield
Stage #1: glycinium trifluoroacetate With thionyl chloride In ISOPROPYLAMIDE at 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride In ISOPROPYLAMIDE at 0 - 20℃; for 96h;	97%

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5)

Conditions	Yield
With thionyl chloride In acetic acid	93.4%
With sulfuric acid; acetic anhydride
With thionyl chloride In acetic acid

Methoxyacetyl chloride (38870-89-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-Methoxyacetamido-2,4,6-triiodoisophthaloyl chloride (76350-03-3)

Conditions	Yield
In 1,4-dioxane at 80 - 90℃;	93%
In N,N-dimethyl acetamide at 10 - 20℃; for 24h;	90.2%
In N,N-dimethyl acetamide at 20℃; for 20h; Cooling with ice;	86%

(S)-2-acetoxypropanoyl chloride (36394-75-9) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → S-(-)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride (60166-91-8)

Conditions	Yield
In N,N-dimethyl acetamide at 0 - 20℃; Inert atmosphere;	92.3%
In N,N-dimethyl acetamide at 0 - 20℃; for 38h; Inert atmosphere;	91.4%
Stage #1: (S)-2-acetoxypropanoyl chloride In N,N-dimethyl acetamide at -2 - 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride; metanol at 12℃; for 6h; Stage #3: With 2-ethoxy-ethanol more than 3 stages;	90%
Stage #1: (S)-2-acetoxypropanoyl chloride In N,N-dimethyl acetamide at -2 - 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride; metanol In N,N-dimethyl acetamide at 12℃; for 6h; Stage #3: With 2-ethoxy-ethanol more than 3 stages;	89%
With N,N-dimethylacetamide hydrochloride In ISOPROPYLAMIDE at 10 - 25℃;

2-acetoxypropionyl chloride (38939-83-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → L-5-(2-acetoxy-propionylamino)-2,4,6-triiodo-isophthalic acid dichloride

Conditions	Yield
Zinc chloride In dichloromethane	90.6%
In ISOPROPYLAMIDE; water; acetone

2-methoxyacetic acid (625-45-6) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-Methoxyacetamido-2,4,6-triiodoisophthaloyl chloride (76350-03-3)

Conditions	Yield
Stage #1: 2-methoxyacetic acid With bis(trichloromethyl) carbonate In dichloromethane for 3h; Reflux; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride In dichloromethane; N,N-dimethyl acetamide; water for 5.5h;	90%
With thionyl chloride In water; N,N-dimethyl-formamide

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) + malonoyl dichloride (1663-67-8) → 5,5′-[malonylbis(azanediyl)]bis(2,4,6-triiodoisophthaloyl dichloride) (79944-44-8)

Conditions	Yield
In tetrahydrofuran at 20 - 50℃; Inert atmosphere;	89.4%
In tetrahydrofuran for 6h; Heating;	83%
In 1,4-dioxane	81%

[(4-aminophenyl)ethoxycarbonylmethylamino]acetic acid ethyl ester (112335-76-9) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → C36H40I3N5O10 (915228-76-1)

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide at 20℃; for 24h;	85%

tetrahydrofuran-2-carbonyl chloride (52449-98-6) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → N-[3,5-Bis(chlorocarbonyl)-2,4,6-triiodo-phenyl]tetrahydro-2-furancarboxamide (153714-17-1)

Conditions	Yield
In tetrahydrofuran; n-heptane for 6.5h; Heating;	81%
In tetrahydrofuran

ethylenediamine (107-15-3) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-N,N'-bis-(2-aminoethyl)-2,4,6-triiodoisophthalamide (869339-38-8)

Conditions	Yield
Stage #1: ethylenediamine; 5-amino-2,4,6-triiodoisophthalic acid dichloride In tetrahydrofuran at 20℃; for 15h; Stage #2: With lithium hydroxide In ethanol; water pH=8.0;	77%

1-amino-2-propene (107-11-9) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-3-allylcarbamoyl-2,4,6-triiodobenzoyl chloride (1071506-72-3)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 12h; Solvent; Cooling with ice;	63%
In tetrahydrofuran at 0℃; for 10h;	60%

N-methyl-N-allylamine (627-37-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 3-(allyl-methyl-carbamoyl)-5-amino-2,4,6-triiodo-benzoyl chloride (946506-01-0)

Conditions	Yield
In tetrahydrofuran at 50℃; for 18h;	59%
In tetrahydrofuran at 50℃;

3-Amino-1,2-propanediol (616-30-8, 13552-31-3) + serinol (534-03-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-N1-(1,3-dihydroxypropan-2-yl)-N3-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (1096689-22-3)

Conditions	Yield
Stage #1: 3-Amino-1,2-propanediol; 5-amino-2,4,6-triiodoisophthalic acid dichloride With triethylamine In N,N-dimethyl acetamide at -24 - 2℃; for 24h; Stage #2: serinol In N,N-dimethyl acetamide at 0 - 40℃; for 44h;	57%
Stage #1: 3-Amino-1,2-propanediol; 5-amino-2,4,6-triiodoisophthalic acid dichloride With triethylamine In ISOPROPYLAMIDE at -24 - 2℃; Stage #2: serinol In ISOPROPYLAMIDE at 0 - 40℃;
With triethylamine In water; 2,4-dichlorophenoxyacetic acid dimethylamine

phosgene (75-44-5) + ethylenediamine (107-15-3) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride

Conditions	Yield
Stage #1: phosgene; 5-amino-2,4,6-triiodoisophthalic acid dichloride In 1,4-dioxane; toluene at 60℃; for 24h; Stage #2: ethylenediamine In tetrahydrofuran at 20℃; for 25h; Stage #3: With lithium hydroxide In water pH=8.0;	53%
Stage #1: phosgene; 5-amino-2,4,6-triiodoisophthalic acid dichloride In 1,4-dioxane; toluene at 60℃; for 24h; Stage #2: ethylenediamine In tetrahydrofuran at 20℃; for 25h; Stage #3: With lithium hydroxide In water pH=8.0;	53%

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) + methylamine (74-89-5) → 5-amino-2,4,6-triiodo-3-N-methylaminocarbonylbenzoic acid chloride (51935-29-6)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 48h;	52%

serinol (534-03-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → S-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide (60166-98-5)

Conditions	Yield
for 0.5h; Milling;	47%
In N,N-dimethyl acetamide for 16h; Ambient temperature;

3-Amino-1,2-propanediol (616-30-8, 13552-31-3) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
In N,N-dimethyl acetamide for 16h; Ambient temperature;
With triethylamine In N,N-dimethyl acetamide at 50℃; for 3.5h; Cooling with ice;

morpholine (110-91-8) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → [3-amino-2,4,6-triiodo-5-(morpholine-4-carbonyl)-phenyl]-morpholin-4-yl-methanone (956914-71-9)

Conditions	Yield
In tetrahydrofuran at 20℃;

N-methyl-N-allylamine (627-37-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → N,N'-diallyl-5-amino-2,4,6-triiodo-N,N'-dimethyl-isophthalamide (946506-02-1)

Conditions	Yield
In tetrahydrofuran at 20℃;

Upstream product

• 35453-19-1 2,4,6-triiodo-5-aminoisophthalic acid 
• 99-31-0 5-aminoisophthalic acid 
• 37091-73-9 2-chloro-1,3-dimethylimidazolinium chloride 
• 618-88-2 5-nitrobenzene-1,3-dicarboxylic acid 

Downstream Products

• 76801-93-9 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 
• 60166-98-5 S-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide 
• 153714-17-1 N-[3,5-Bis(chlorocarbonyl)-2,4,6-triiodo-phenyl]tetrahydro-2-furancarboxamide 
• 79944-44-8 5,5′-[malonylbis(azanediyl)]bis(2,4,6-triiodoisophthaloyl dichloride) 
• 956914-71-9 [3-amino-2,4,6-triiodo-5-(morpholine-4-carbonyl)-phenyl]-morpholin-4-yl-methanone 
• 946506-02-1 N,N'-diallyl-5-amino-2,4,6-triiodo-N,N'-dimethyl-isophthalamide 
• 77203-02-2 5-chloroacetylamino-2,4,6-triiodoisophthaloyl chloride 
• 869339-38-8 5-amino-N,N'-bis-(2-aminoethyl)-2,4,6-triiodoisophthalamide 
• 31122-75-5 5-acetamido-2,4,6-triiodoisophthaloyl dichloride 
• 99139-32-9 5-aminodiallylamino-2,4,6-triiodoisophthalamide 
• 173772-55-9 5-[(5-Methoxy-1,5-dioxopentyl)amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid, Diacid chloride 
• 31127-80-7 N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide 
• 128286-13-5 5-[2-isopropyl-1,3-dioxane-5-carboxamido]-2,4,6-triiodo-isophthaloyl dichloride 
• 78314-12-2 2-((3,5-bis (chlorocarbonyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate 

Relevant academic research and scientific papers

Optimisation of the preparation and isolation of 5-amino-2,4,6-triiodoisophthalic acid dichloride

A scaleable process for the chlorination of 5-amino-2,4,6-triiodoisophthalic acid to the corresponding acid chloride, a building block for the synthesis of iodinated X-ray contrast agents, has been developed. Two dimeric byproducts have been isolated and assigned structures consistent with an amide and an anhydride. Hydrolysis of the N-sulfinyl intermediate and simultaneous crystallisation of the phthalic acid chloride have been optimised by applying fractional factorial design.

Iopamidol synthesis and preparation of iopamidol synthesis intermediate

The invention relates to the technical field of chemical synthesis processes, particularly to iopamidol synthesis and preparation of an iopamidol synthesis intermediate. According to the present invention, by adjusting the feeding weight ratio, optimizing the reaction conditions and improving the iopamidol synthesis route, the requirements on the compound reaction conditions are low, the control of the reaction is simple, and the yield is increased while the quality of the intermediate product is greatly improved so as to reduce the process control difficulty in the iopamidol production process and improve the quality and the qualification rate of iopamidol; and various steps of the preparation process are simple, the solvents and the process conditions are safe and easy to perform, the environmental protection production is achieved, and the method has broad application prospects.

9 - Azabicyclo [3.3.1] nonane coupling [...] compound and its preparation method and use thereof (by machine translation)

The invention discloses a 9 - azabicyclo [3.3.1] nonane coupling [...] compound, its preparation method comprises the following steps: in the organic solvent, the 9 - nitrogen (6' - amino) oneself amidogen - 9 - 9 - azabicyclo [3.3.1] nonane - 3 α - alkyl amino formic acid benzene and chloro acetyl three iodo aniline derivatives in accordance with the 1: 1.0 - 1.5 molar ratio, for the catalysis of cesium hydroxide at room temperature reaction in the 20 - 30 the H, obtained as the product of the 9 - azabicyclo [3.3.1] nonane coupling [...] compound. The invention also discloses the use thereof: a contrast agent for early diagnosis of breast cancer. (by machine translation)

Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

BIODEGRADABLE COMPUTED TOMOGRAPHY CONTRAST AGENTS

Biodegradable computed tomography (CT) contrast agents comprising a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide are described herein. The contrast agents can be used to image a tissue region by administering an effective amount of the biodegradable CT contrast agent to a subject, allowing a sufficient amount of time for the biodegradable CT contrast agent to enter the tissue region, and performing x-ray computed tomography imaging of the tissue region of the subject.

The synthesis and evaluation of trimeric X-ray contrast agents

Novel trimeric iodinated contrast agents with low osmolality have been prepared and evaluated with the aim of improving the already good safety profile of such agents. While the aim of low osmolality was achieved, the viscosity of the trimeric agents was found to be generally higher than current dimeric agents in clinical use.

CONTRAST AGENTS

The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a triamine alkyl central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

CONTRAST AGENTS

The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a tris(aminoalkyl)amine group allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.

Effect of contrast agent charge on visualization of articular cartilage using computed tomography: Exploiting electrostatic interactions for improved sensitivity

(Chemical Equation Presented) The synthesis and evaluation of a new class of cationic iodinated contrast agents for the imaging of cartilage using computed tomography (CT) are described. In direct comparisons with anionic contrast agents, the cationic contrast agents afforded higher equilibrium concentrations in the articular cartilage of ex vivo rabbit femurs and thus greater imaging sensitivity. Variations in CT intensity across the sample reflected the inhomogeneous distribution of glycosaminoglycans in the tissue as confirmed by histological analysis. We anticipate that this work represents the first step in the development of sensitive, nondestructive CT-based methods to characterize the biochemical properties of cartilage using cationic contrast agents.

TRISUBSTITUTED TRIAZAMACROCYCLI C COMPOUNDS AND THEIR USE AS CONTRAST AGENTS

The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a saturated triaza cyclic central moiety containing carbonyl functions allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.