76801-93-9

Usage

Uses

Used in Pharmaceutical Industry:
5-Amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide is used as an intermediate for the industrial preparation of non-ionic X-ray contrast agents. These agents, such as Iohexol, Ioversol, Ioxilan, and Iopamidol, are essential in medical imaging, particularly in X-ray and computed tomography (CT) scans, to enhance the visibility of internal structures and facilitate the diagnosis of various conditions.
5-Amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide's role as an intermediate in the synthesis of these contrast agents is crucial, as it contributes to the development of safer and more effective imaging tools that minimize the risk of adverse reactions and improve patient outcomes. Its unique structure allows for the creation of non-ionic agents with reduced osmotic pressure, making them more tolerable for patients and reducing the likelihood of side effects during medical imaging procedures.

Synthetic route

5-Amino-N,N'-bis[2,3-dihydroxypropyl]-1,3-benzenedicarboxamide (76820-35-4) + sodium phosphate → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
In water	86%

5-Amino-N,N'-bis[2,3-dihydroxypropyl]-1,3-benzenedicarboxamide (76820-35-4) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
With potassium iodate; sulfuric acid; iodine; sodium sulfate In water at 65 - 80℃; for 47h;	86%
With Iodine monochloride In water Product distribution / selectivity; Industry scale;
With Iodine monochloride In water Product distribution / selectivity; Industry scale;
With Iodine monochloride at 50℃; for 6h;

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;

5-aminoisophthalic acid (99-31-0) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 74 percent / aq. potassium iododichloride / H2O / 18 h / 55 - 60 °C 2: 92 percent / thionyl chloride 3: N,N-dimethyl-acetamide / 16 h / Ambient temperature View Scheme

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 92 percent / thionyl chloride 2: N,N-dimethyl-acetamide / 16 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / ethyl acetate / 20 h / 70 - 80 °C 2: triethylamine / N,N-dimethyl acetamide / 3.5 h / 50 °C / Cooling with ice View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)isophthalamide hydrochloride (203515-86-0) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
With Iodine monochloride at 60 - 85℃; pH=3 - 0.5;
With Iodine monochloride; sodium hydroxide In water at 65 - 80℃; pH=2 - 3;
With Iodine monochloride; sodium hydroxide In water at 20 - 80℃; pH=2 - 3;

5-nitro-N,N'-bis-(2,3-dihydroxypropyl)isophthalamide (76820-34-3) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
	9.3 g (76%)
Multi-step reaction with 2 steps 1: 5%-palladium/activated carbon; hydrogen / 70 °C / 9000.9 Torr / Autoclave 2: Iodine monochloride / 6 h / 50 °C View Scheme

dimethyl 5-nitroisophthalate (13290-96-5) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium methylate / methanol / 80 h 2: hydrogen / water / 10 h / 11251.1 Torr 3: iodine; potassium iodate; sodium sulfate; sulfuric acid / water / 47 h / 65 - 80 °C View Scheme
Multi-step reaction with 3 steps 1: sodium methylate / methanol / 20 - 50 °C 2: 5%-palladium/activated carbon; hydrogen / 70 °C / 9000.9 Torr / Autoclave 3: Iodine monochloride / 6 h / 50 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + acetic anhydride (108-24-7) → 5-amino-N,N'-bis[2,3-bis(acetyloxy)propyl]2,4,6-triiodo-1,3-benzenedicarboxamide (76801-94-0)

Conditions	Yield
With pyridine at 0 - 20℃;	100%
With dmap In ethyl acetate for 2h; Reflux;	90%
With pyridine for 6h; Ambient temperature; Yield given;
70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h;
With pyridine

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + chloroacetyl chloride (79-04-9) → 5-chloroacetamido-N,N'-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide (77203-11-3)

Conditions	Yield
Stage #1: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide; chloroacetyl chloride; 1-methyl-pyrrolidin-2-one at 35 - 50℃; for 6h; Stage #2: With water Product distribution / selectivity;	97%
In N,N-dimethyl acetamide at 10 - 50℃; for 3.5h;	90%
In N,N-dimethyl acetamide at 10 - 50℃; for 3.5h;	90%

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + trifluoroacetic anhydride (407-25-0) → N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-(2,2,2-trifluoroacetamido)isophthalamide (167630-07-1)

Conditions	Yield
With dmap In toluene at 40℃; for 24h;	94%

formic acid (64-18-6) + 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N,N'-bis(2,3-dihydroxypropyl)-5-formylamino-2,4,6-triiodoisophthalamide (186753-11-7)

Conditions	Yield
With acetic anhydride at 2.5 - 20℃; Inert atmosphere;	81.5%

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + acetic anhydride (108-24-7) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-(3-acetamido-5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylcarbamoyl)-2,4,6-triiodobenzamido)-propane-1,2-diyl diacetate + 5-acetamido-N,N′-bis-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl-2,4,6-triiodoisophthaldiamide + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide

Conditions	Yield
Stage #1: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide; acetic anhydride With toluene-4-sulfonic acid In acetone for 0.25h; Reflux; Stage #2: With sodium hydroxide In water; acetone	A 70% B 32% C 17% D n/a E n/a

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + acetic anhydride (108-24-7) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide

Conditions	Yield
Stage #1: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide; acetic anhydride With toluene-4-sulfonic acid In acetone for 0.25h; Reflux; Stage #2: With sodium hydroxide In water; acetone Stage #3: With sulfuric acid In water; acetone pH=0;	A 70% B n/a C n/a

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → 5-amino-N-(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide

Conditions	Yield
With sulfuric acid; iodine; iodic acid In water at 85℃; for 24h; Temperature;	45%

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + acetic anhydride (108-24-7) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-(3-acetamido-5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylcarbamoyl)-2,4,6-triiodobenzamido)-propane-1,2-diyl diacetate + 5-acetamido-N,N′-bis-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl-2,4,6-triiodoisophthaldiamide

Conditions	Yield
Stage #1: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide; acetic anhydride With toluene-4-sulfonic acid In acetone for 0.25h; Reflux; Stage #2: With sodium hydroxide In water; acetone pH=Ca. 14;	A 38% B 39% C 17%

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N-[3,5-bis-(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodo-phenyl]-succinamic acid (188655-32-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h 2: N,N-dimethyl-acetamide / 50 h / Ambient temperature 3: 62.9 g / NaOH / methanol; H2O / 5 h / 50 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → {3-[3,5-bis-(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodo-phenylcarbamoyl]-propionylamino}acetic acid

Conditions	Yield
Multi-step reaction with 5 steps 1: 70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h 2: N,N-dimethyl-acetamide / 50 h / Ambient temperature 3: 62.9 g / NaOH / methanol; H2O / 5 h / 50 °C 4: EDC / dimethylformamide / 23 h / Ambient temperature 5: 3.97 g / RP-18 / methanol; H2O View Scheme
Multi-step reaction with 4 steps 1: 70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h 2: N,N-dimethyl-acetamide / 50 h / Ambient temperature 3: 62.9 g / NaOH / methanol; H2O / 5 h / 50 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → 3-{3-[3,5-Bis-(2,3-dihydroxy-propylcarbamoyl)-2,4,6-triiodo-phenylcarbamoyl]-propionylamino}-propionic acid

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h 2: N,N-dimethyl-acetamide / 50 h / Ambient temperature 3: 62.9 g / NaOH / methanol; H2O / 5 h / 50 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → {3-[3,5-Bis-(2,3-dihydroxy-propylcarbamoyl)-2,4,6-triiodo-phenylcarbamoyl]-propionylamino}-acetic acid tert-butyl ester

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h 2: N,N-dimethyl-acetamide / 50 h / Ambient temperature 3: 62.9 g / NaOH / methanol; H2O / 5 h / 50 °C 4: EDC / dimethylformamide / 23 h / Ambient temperature View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N-[3,5-Bis-(2,3-diacetoxy-propylcarbamoyl)-2,4,6-triiodo-phenyl]-succinamic acid methyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 deg C, 2 h; 80 deg C, 3 h; rt, 15 h 2: N,N-dimethyl-acetamide / 50 h / Ambient temperature View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → 5-(N-allyl-2,2,2-trifluoroacetamido)-N,N'-bis-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (171897-75-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 94 percent / DMAP / toluene / 24 h / 40 °C 2: 84 percent / K2CO3 / N,N-dimethyl-acetamide / 24 h / Ambient temperature View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → 5--N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (171897-76-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / DMAP / toluene / 24 h / 40 °C 2: 84 percent / K2CO3 / N,N-dimethyl-acetamide / 24 h / Ambient temperature 3: 94 percent / aq. Br2, Amberlite IRA-68 / 0 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → 5,5'-(N-acetyl-2-hydroxypropane-1,3-diyldiamino)bis

Conditions	Yield
Multi-step reaction with 4 steps 1: 94 percent / DMAP / toluene / 24 h / 40 °C 2: 84 percent / K2CO3 / N,N-dimethyl-acetamide / 24 h / Ambient temperature 3: 94 percent / aq. Br2, Amberlite IRA-68 / 0 °C 4: H2O / 48 h / Ambient temperature; pH=12.0 View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → acetic acid 2-acetoxy-3-[3-(2,3-diacetoxy-propylcarbamoyl)-2,4,6-triiodo-5-isocyanato-benzoylamino]-propyl-1-ester (136452-99-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → <3,5-bis<<<2,3-bis(acetyloxy)propyl>amino>carbonyl>-2,4,6-triiodophenyl>carbamic acid, oxyranylmethyl ester (136453-00-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h / Ambient temperature View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → <3,5-bis<<<2,3-bis(acetyloxy)propyl>amino>carbonyl>-2,4,6-triiodophenyl>carbamic acid, (S)-oxyranylmethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → <3,5-bis<<<2,3-bis(acetyloxy)propyl>amino>carbonyl>-2,4,6-triiodophenyl>carbamic acid, (R)-oxiranylmethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N,N'-bis<2,3-bis(acetyloxy)propyl>-5-<4-(hydroxymethyl)-2-oxo-3-oxazolidinyl>-2,4,6-triiodo-1,3-benzenedicarboxamide (136453-01-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h / Ambient temperature 4: 75 percent / pyridine / 2 h / 75 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N,N'-bis<2,3-bis(acetyloxy)propyl>-5-<4(R)-(hydroxymethyl)-2-oxo-3-oxazolidinyl>-2,4,6-triiodo-1,3-benzenedicarboxamide

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h / Ambient temperature 4: pyridine / 2 h / 75 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N,N'-bis<2,3-bis(acetyloxy)propyl>-5-<4(S)-(hydroxymethyl)-2-oxo-3-oxazolidinyl>-2,4,6-triiodo-1,3-benzenedicarboxamide

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h / Ambient temperature 4: pyridine / 2 h / 75 °C View Scheme

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) → N,N'-bis(2,3-dihydroxypropyl)-5-<4-(hydroxymethyl)-2-oxo-3-oxazolidinyl>-2,4,6-triiodo-1,3-benzenedicarboxamide

Conditions	Yield
Multi-step reaction with 5 steps 1: pyridine / 6 h / Ambient temperature 2: dioxane; toluene / 15 h / 60 °C 3: phenylmercuric acetate / dioxane / 4 h / Ambient temperature 4: 75 percent / pyridine / 2 h / 75 °C 5: 73 percent / MeONa / methanol / 1 h View Scheme

Upstream product

• 76820-35-4 5-Amino-N,N'-bis[2,3-dihydroxypropyl]-1,3-benzenedicarboxamide 
• 13290-96-5 dimethyl 5-nitroisophthalate 
• 76820-34-3 5-nitro-N,N'-bis-(2,3-dihydroxypropyl)isophthalamide 
• 203515-86-0 5-amino-N,N'-bis(2,3-dihydroxypropyl)isophthalamide hydrochloride 
• 35453-19-1 2,4,6-triiodo-5-aminoisophthalic acid 
• 99-31-0 5-aminoisophthalic acid 
• 616-30-8 3-Amino-1,2-propanediol 
• 37441-29-5 5-amino-2,4,6-triiodoisophthalic acid dichloride 

Downstream Products

• 31127-80-7 N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide 
• 174416-65-0 C₂₄H₂₈I₃N₃O₁₁ 
• 66108-95-0 iohexol 
• 87785-51-1 5-(acetoxyacetylamino)-N,N'-bis(2,3-diacetoxypropyl)-2,4,6-triiodoisophthalamide 
• 78649-41-9 iomeprol 
• 87771-40-2 ioversol 
• 186753-11-7 N,N'-bis(2,3-dihydroxypropyl)-5-formylamino-2,4,6-triiodoisophthalamide 
• 77203-11-3 5-chloroacetamido-N,N'-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide 

Relevant academic research and scientific papers

Contrast medium of the impurity F synthetic method and its impurity G contrast medium, impurity H and impurity M application in the synthesis of

The invention relates to a synthesis method of contrast medium impurities, in particular to a contrast medium impurity F synthetic method and its in the contrast medium impurity G, impurity H and M application in the synthesis of the impurity, which belongs to the field of medical technology. The method is to 5 - nitro - 1, 3 - benzene dicarboxylic acid dimethyl ester (formula 2 compound) and 2, 3 - dihydroxy propylamine as raw materials of formula 3 compound, type 3 compound with hydrogen reduction reaction [...] 4 compound, of formula 4 with a compound obtained by reaction of the impurity F [...] contrast medium. The invention relates to 5 - nitro - 1, 3 - benzene dicarboxylic acid dimethyl ester (formula 2 compound) as the starting material, the synthesis of 5 - amino - N, double-N' - (2, 3 - dihydroxy-propyl) - diiodo - 1, 3 - benzene dicarboxylic amide (formula 1 compounds) and then to of formula 1 as the starting material for the synthesis of impurity G, impurity H and impurity M, for the contrast medium quality control to provide acceptable impurity reference substance.

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)

IODINATION PROCESS FOR THE PREPARATION OF 3,5-DISUBSTITUTED-2,4,6-TRIIODO AROMATIC AMINES COMPOUNDS

The invention discloses a improved process for the preparation of 3,5-disubstituted- 2,4,6-triiodo aromatic amines of formula (II), wherein R1 and R2 are defined as herein. The compounds of formula (II) are the key intermediates for the synthesis of a series of non-ionic contrast agents such as Iopamidol, Iohexol and Iodixanol. The process comprises reacting chlorine-free iodinating reagents with 3,5-disubstituted-2,4,6-triiodo aromatic amines to obtain 3,5-disubstituted-2,4,6-triiodo aromatic amines of formula (II), wherein the molar yield of the iodination reaction can reach to 89%.

CONTINUOUS PROCESS OF PREPARING INTERMEDIATE FOR NON-IONIC X-RAY CONTRAST AGENTS

This invention relates to an improved method for the synthesis of 5-amino-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (Compound B), an intermediate in the industrial preparation of non-ionic X-ray contrast agents. In particular, it relates to a continuous process of the iodination reaction followed by the purification of Compound B.

Decolorizing 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide, a contrast media intermediate

This invention relates to an improved method for the synthesis of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (Compound B), an intermediate in the industrial preparation of non-ionic X-ray contrast agents. In particular, it relates to a process for decolorizing said intermediate.

CRYSTALLIZATION OF AN INTERMEDIATE FOR SYNTHESIZING NON-IONIC X-RAY CONTRAST AGENTS

This invention relates generally to the crystallization process of 5-amino-N,N′-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide (“Compound B”), an iodinated intermediate in the preparation of non-ionic X-ray contrast agents. The instant process utilizes a nanofiltration system to pass through low molecular weight salt, thereby reducing the solubility of Compound B in the retentate. This process increases supersaturation of the mother liquor and improves crystal growth in the crystallization following the initial one. The process of the present invention is useful in increasing the overall crystallization yield of Compound B in an industrial manufacturing process.

Improvements in crystallization of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6,-triiodo-isophthalamide, an intermediate for synthesizing non-ionic X-ray contrast agents

This invention relates to the crystallization process of 5-amino-N, N'- bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide ("Compound B"), an iodinated intermediate in the preparation of non-ionic X-ray contrast agents. The instant process utilizes a nanofiltration system to pass through low molecular weight salt, thereby reducing the solubility of Compound B in the retentate. This process increases supersaturation of the mother liquor and improves crystal growth in the crystallization following the initial one. The process of the present invention is useful in increasing the overall crystallization yield of Compound B in an industrial manufacturing process.

Yellow polymorph of 5-amino-2,4,6-triiodo-n,n′-bis(2-3-dihydroxypropy)-isophthalamide

The yellow polymorph of 5-amino-2,4,6-triiodo-N,N′-bis(2,3-dihydroxypropyl)-isophthalamide is described.

Urea-linked, iodinated bis phenyl compounds for X-ray contrast media

The invention provides iodinated bis phenyl compounds, useful as X-ray contrast agents, of formula I STR1 (wherein each C6 R5 moeity may be the same or different; each R denotes a hydrogen or iodine atom or a group M, two or three non-adjacent R groups on each C6 R5 moiety denoting iodine atoms and one, two or three R groups on each C6 R5 moiety denoting M groups; X denotes a group providing a 1, 2 or 3 atom chain linking the two C6 R5 groups, preferably where X is or contains in the bridging chain a carbonyloxy group each C6 R5 group being a triodophenyl group or a group in which each R is other than hydrogen; and each M is independently a non-ionic hydrophilic moiety, M preferably being a non-ionic hydrophilic moiety comprising a monohydroxy- or polyhydroxy-alkyl group) and isomers, especially stereoisomers and rotamers, thereof.

Heterocyclic Nonionic X-ray Contrast Agents. 3. The Synthesis of 5--2,4,6-triiodo-1,3-benzenedicarboxamide Derivatives

The syntheses of 2,4,6-triiodo-1,3-benzenedicarboxamide analogs, 12c, 12e, and 17c, of interest as X-ray diagnostic agents and in which the 5 position is linked to the N atom of a 4-(hydroxymethyl)-oxazolidin-2-one moiety, are described.The heterocycle was built from suitably protected 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid derivatives by a three-step procedure consisting of (1) phosgene treatment to obtain the corresponding isocyanates, (2) phenylmercuric chloride-catalyzed addition of glycidol (10) resulting in glycidil carbamates, and (3) pyridine-catalyzed intramolecular N-alkylation, followed by deprotection, to obtain the oxazolidin-2-ones.The intramolecular N-alkylation reaction was highly regioselective and was not appreciably accompanied by O-alkylation products under the experimental conditions employed.The two carboxamide nitrogen atoms in the intermediates and end products carry either 2,3-dihydroxypropyl or 1,3-dihydroxypropyl residues.These highly congested benzenoid compounds exhibited interesting NMR spectral features due to atropisomerism arising from hindrance to free rotation about the three single bonds that link the aromatic moiety to the N-containing functionalities.