Iopentol, Compound-5411, Ivepaque, Imagopaque

N,N'-Bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxy-3-methoxypropyl)acetamido]-2,4,6-triiodoisophthalamide; 5-[Acetyl(2-hydroxy-3-methoxypropyl)amino]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide

89797-00-2

C20-H28-I3-N3-O9

835.174

Amersham Health (Originator), Nycomed Pharma (Originator), Daiichi Pharmaceutical (Licensee), Sanofi-Synth閘abo (Licensee)

Contrast Mediums, DIAGNOSTIC AGENTS

Launched-1991

　

Acta Chem Scand

An observation of cationic influence on the N/O alkylation selectivity in the alkylation of a compound containing several nucleophilic sites

Acetylation of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (I) in refluxing acetic anhydride in the presence of p-toluenesulfonic acid affords acetamide (II). The title compound is then obtained by alkylation of acetamide (II) with 1-chloro-3-methoxy-2-propanol (III). The selectivity in the alkylation at the acetamide N has been improved with the addition of several metallic cations, the best results being obtained with calcium ions.

Bjoersvik, H.-R.; et al.

Bjoersvik, H.-R.; et al.; An observation of cationic influence on the N/O alkylation selectivity in the alkylation of a compound containing several nucleophilic sites. Acta Chem Scand 1994, 48, 7, 582

Acta Chem Scand1994,48,(7):582

J Chromatogr

Preparative liquid chromatography in the field of X-ray contrast agents

Alternatively, 5-acetamido-2,4,6-triiodoisophthalic acid (I) is alkylated with 1-chloro-3-methoxy-2-propanol (II) to produce (III). After protection of the alcoholic hydroxyl group as the acetate ester (IV), the carboxyl groups are activated as the corresponding acid chloride (V) with SOCl2. Coupling of (V) with 3-amino-1,2-propanediol (VI) then produces the title amide.

Skjoeld, W.; Berg, A.

Skjoeld, W.; Berg, A.; Preparative liquid chromatography in the field of X-ray contrast agents. J Chromatogr 1986, 366, 299

J Chromatogr1986,366,():299

Org Process Res Dev

A selective process for N-alkylation in competition with O-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes

In an improved method, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent alkylation of (II) with 1-chloro-3-methoxy-2-propanol (III) yields regioselectively the N-alkylated acetamide (IV). The borate groups of (IV) are finally removed upon quenching with diluted HCl.

Bjoersvik, H.-R.; et al.

Bjoersvik, H.-R.; et al.; A selective process for N-alkylation in competition with O-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes. Org Process Res Dev 2001, 5, .ID_RE

Org Process Res Dev2001,5,(5):472

EP 0105752

X-Ray contrast agents

Acetylation of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (I) in refluxing acetic anhydride in the presence of p-toluenesulfonic acid affords acetamide (II). The title compound is then obtained by alkylation of acetamide (II) with 1-chloro-3-methoxy-2-propanol (III). The selectivity in the alkylation at the acetamide N has been improved with the addition of several metallic cations, the best results being obtained with calcium ions.

Wille, K. (Amersham plc)

Wille, K. (Amersham plc); X-Ray contrast agents. EP 0105752

EP 0105752,,():

WO 9808805

Process for the preparation of contrast agents

Acetylation of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (I) in refluxing acetic anhydride in the presence of p-toluenesulfonic acid affords acetamide (II). The title compound is then obtained by alkylation of acetamide (II) with 1-chloro-3-methoxy-2-propanol (III). The selectivity in the alkylation at the acetamide N has been improved with the addition of several metallic cations, the best results being obtained with calcium ions.

Cockbain, J.R.M.; Gulbrandsen, T.; Ingvoldstad, O.E.; Holmaas, L.T. (Amersham plc)

Cockbain, J.R.M.; Gulbrandsen, T.; Ingvoldstad, O.E.; Holmaas, L.T. (Amersham plc); Process for the preparation of contrast agents. WO 9808805

WO 9808805,,():

GB 2331098

An N-alkylation

In an improved method, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent alkylation of (II) with 1-chloro-3-methoxy-2-propanol (III) yields regioselectively the N-alkylated acetamide (IV). The borate groups of (IV) are finally removed upon quenching with diluted HCl.

Priebe, H. (Amersham plc)

Priebe, H. (Amersham plc); An N-alkylation. GB 2331098

GB 2331098,,():