Nycomed Imaging As

Amersham Health As

Ge Healthcare As

Trygve Gulbrandsen

Odd Einar Ingvoldstad

Lars Terje Holmaas

Per Strande

Arne Berg

Harald Dugstad

Michel Gacek

Einar Odd Ingvoldstad

William Thielking

William Thieking

This invention relates generally to non-ionic X-ray contrast agents. It further relates to the synthesis of iodixanol. In particular, it relates to alternative dimerisation reagents in the conversion of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide ('Compound A') to iodixanol.

Alternative dimerisation reagents for synthesis of iodixanol

The invention provides a process by which ultra low salt content triiodinated aromatic compounds may be isolated from a highly acidic hot triiodinationractionreactionmedium in a straightforward fashion. The process involves increasing the pH toabove 5a value in the range of 3 to 7with sodium hydroxide, addition of sodium bisulphite and/or sodium dithionite, addition of seed crystals, cooling slowly, and washing the collected precipitate with water.

Preparation of tri-iodo benzene compounds

Process for the preparation of contrast agents The invention provides a process for the preparation of an N-alkyl-acylamino-phenyl-carboxylic acid or carboxylic acid derivative by liquid phase acylation and subsequent N-alkylation of a corresponding amino-phenyl-carboxylic acid (or carboxylic acid derivative), the improvement comprising the addition of an alkylating agent to a solution containing the reaction products of said acylation, to effect said N-alkylation.

Process for the preparation of contrast agents

The invention provides a process by which ultra low salt content triiodinated aromatic compounds may be isolated from a highly acidic hot triiodination raction medium in a straightforward fashion. The process involves increasing the pH to above 5 with sodium hydroxide, addition of sodium bisulphite and/or sodium dithionite, addition of seed crystals, cooling slowly, and washing the collected precipitate with water.

The invention provides a process for the preparation of an N-alkyl-acylamino-phenyl-carboxylic acid or carboxylic acid derivative by liquid phase acylation and subsequent N-alkylation of a corresponding amino-phenyl-carboxylic acid (or carboxylic acid derivative), the improvement comprising the addition of an alkylating agent to a solution containing the reaction products of said acylation, to effect said N-alkylation.

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Kolsas, Norway

Trygve Gulbrandsen