Method for reducing aminoisophthalic acid bisamide related...

C - Chemistry – Metallurgy – 07 – C

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C07C 231/24 (2006.01) C07C 237/32 (2006.01) A61K 49/00 (2006.01)

Patent

CA 2710095

This invention relates generally to the preparation of non-ionic X-ray contrast agents, iohexol, ioversol, and iodixanol. It further relates to a method for improving the purity of 5-amino-N,N'-bis(2,3-dihydroxypropyl)-isophthalamide (or ABA), an intermediate in the industrial preparation of these non-ionic X-ray contrast agents. In particular, it relates to a method for significantly removing ABA monomethylester and ABA dimer from ABA by hydrolyzing ABA under a pH between about 12 to about 13 in an aqueous medium to convert ABA monomethylester to ABA monoacid, before the iodination reaction of ABA.

La présente invention a pour objet de manière générale la préparation d'agents de contraste non ioniques pour radiographie X, iohexol, ioversol et iodixanol. Elle a aussi pour objet une méthode pour améliorer la pureté du 5-amino-N,N'-bis(2,3-dihydroxypropyl)isophtalamide (ou ABA), un intermédiaire dans la préparation industrielle de ces agents de contraste non ioniques pour radiographie X. Cette invention a pour objet en particulier une méthode pour éliminer de manière significative l'ester monométhylique d'ABA et le dimère d'ABA par hydrolyse de l'ABA à un pH compris entre environ 12 et environ 13 en milieu aqueux, de manière à transformer l'ester monométhylique d'ABA en monoacide d'ABA avant la réaction d'ioduration de l'ABA.

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