Ge Healthcare as

Lars Terje Holmaas

Ole Magne Homestad

Sumihar Silalahi

Hanne Jorunn H Johnsen

Trond Kjernli

Kristin Rypestol

Eli Ryssdal Andersen

Vidar Olaisen

Siw Anette Helle

Mari Brusletten

Lone Omtvedt

Hanne Jorunn Johnsen

This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N&#x2032;-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with propyleneglycol as solvent.

Synthesis of iodixanol in propyleneglycol

This invention relates to the synthesis of iodixanol (1,3-bis(acetamido)-N,N'-bis[3,5-bis(2,3-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl]-2-hydroxypropane), more specifically to the dimerisation of 5-acetamido-N,N&#x2032;-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide with methanol as solvent.

Synthesis of iodixanol in methanol

This invention relates to an improved method for crystallizing 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide ('Compound A'), an intermediate in the industrial preparation of non-ionic X-ray contrast agents. In particular, the present invention provides an industrial process for crystallization of Compound A by evaporating methanol and water from the mother liquor after an initial crystallization of Compound A following the acetylation reaction. Specifically, the mother liquor is maintained at more than about 75% (v/v) of water and less than about 25% (v/v) of alcoholic solvent.

Solvent reduction in crystallisation of intermediate for non-ionic X-ray contrast agents

Process for the production of DTPA-bis(anhydride) by reacting DTPA with acetic anhydride in pyridine under elevated temperature wherein the molar amount of pyridine is equal to or less than 6 times the molar amount of DTPA.

Process for the production of DTPA-bis anhydride

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Spangereid, Norway

Lars Terje Holmaas