Ge Healthcare as

Khalid Hussain

Jan Cervenka

Arne Wang Aabye

Mikkel Jacob Thaning

Andreas Richard Meijer

Sondre Nilsen

Ingvil Gausemel

Silalahi Sumihar

Jarle Andre Haugan

Nikolai Enes

The present invention provides methods for the preparation of compounds useful in in vivo therapeutic and diagnostic applications. In particular, the present invention provides a method for the synthesis of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and also methods for the preparation of metal chelates of DOTA.

DOTA synthesis

The invention describes a process for the purification of iodinated aryl compounds where the purification is performed by continuous crystallization of a crude product in a solvent with addition of anti-solvent. The continuous crystallization process is performed in one or more crystallizers at a temperature up to the boiling point of the content of the crystallizer.

Continuous crystallisation process of iodinated phenyl derivatives

A process for the manufacture of iodixanol by performing a purification process of the crude product in a solvent comprising 1-methoxy-2-propanol. The crude product may be obtained in aqueous solution from dimerization of 5-acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-isophthalamide ('Compound A').

Preparation of iodixanol

The invention describes a process for the purification of iodinated aryl compounds where the purification is performed by continuous crystallization of a crude product in a solvent with removal of at least a fraction of the solvent. The continuous crystallization process is performed in one or more crystallizers at the boiling point of the content of the crystallizer.

This invention relates to the manufacture 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 purification of iodixanol by crystallization by using wet milling.

Crystallization of iodixanol using milling

This invention relates to the manufacture 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 purification of iodixanol by crystallization by using ultrasound.

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Oslo, Norway

Khalid Hussain