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Iopentol, Compound-5411, Ivepaque, Imagopaque

碘喷托Chemical Name: 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
CAS No. 89797-00-2
项目整合开发状态: Launched-1991
项目研究机构: Amersham Health (Originator), Nycomed Pharma (Originator), Daiichi Pharmaceutical (Licensee), Sanofi-Aventis (Licensee)
合成路线: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.
📌 参考资料/链接:
参考文献标题:X-Ray contrast agents
文献作者:Wille,K.(Amersham plc)
参考来源:EP 0105752

📄 详细内容


合成路线: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.

合成路线:In a different strategy,the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II).Subsequent condensation of (II) with epichlorohydrin (III) yields the dimeric adduct (IV).The borate groups of (IV) are finally removed upon quenching with diluted HCl.

合成路线: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 2-chloroethanol (III) yields regioselectively the N-alkylated acetamide (IV).The borate groups of (IV) are finally removed upon quenching with diluted HCl.

参考文献标题:An N-alkylation
文献作者:Priebe,H.(Amersham plc)
参考来源:GB 2331098


合成路线: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.

参考文献标题:Process for the preparation of contrast agents
文献作者:Cockbain,J.R.M.; Gulbrandsen,T.; Ingvoldstad,O.E.; Holmaas,L.T.(Amersham plc)
参考来源:WO 9808805


合成路线: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.

参考文献标题:Preparative liquid chromatography in the field of X-ray contrast agents
文献作者:Skjoeld,W.; Berg,A.
参考来源:J Chromatogr 1986,366299


合成路线: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.

合成路线:In a different strategy,the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II).Subsequent condensation of (II) with epichlorohydrin (III) yields the dimeric adduct (IV).The borate groups of (IV) are finally removed upon quenching with diluted HCl.

合成路线: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 2-chloroethanol (III) yields regioselectively the N-alkylated acetamide (IV).The borate groups of (IV) are finally removed upon quenching with diluted HCl.

参考文献标题: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
文献作者:Bjoersvik,H.-R.; et al.
参考来源:Org Process Res Dev 2001,5(5),472


合成路线: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.
参考文献标题:An observation of cationic influence on the N/O alkylation selectivity in the alkylation of a compound containing several nucleophilic sites
文献作者:Bjoersvik,H.-R.; et al.
参考来源:Acta Chem Scand 1994,48(7),582


产品链接: CAS No. 89797-00-2››