Crystal of diuridine tetraphosphate or salt thereof and...

C - Chemistry – Metallurgy – 07 – H

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C07H 19/10 (2006.01) C07H 21/02 (2006.01)

Patent

CA 2345624

The invention provides crystals of P1,P4-di(uridine 5'- )tetraphosphate or a salt thereof; a process for producing the crystals; and a process for producing P1,P4-di(uridine 5'-)tetraphosphate (U2P4) or a salt thereof from UMP serving as a starting material and by use of DPC and PPi, which process comprises at least one of the following treatment steps: (a) adding UMP diphenylphosphate (UMP-DPP) in divided portions during a step of reaction of UMP-DPP with a PPi- organic alkali salt; (b) carrying out reaction of UMP-DPP with a PPi-organic alkali salt in the presence of a base; and (c) further treating the synthesized U2P4 with an alkali. The crystals of U2P4 or a salt thereof obtained through the process according to the invention have high purity and stability and,a less hygroscopicity as compared with a lyophilized product, to thereby serve as a useful raw material for preparing a pharmaceutical. The process for producing U2P4 or a salt thereof according to the invention realizes high yield and enables large-scale synthesis.

L'invention concerne un cristal stable et à pureté élevée de P<1>,P<4>-di(uridine5'-)tétraphosphate (U2P4) ou un sel de celui-ci ainsi qu'un procédé de préparation dudit cristal qui consiste à purifier un U2P4 brut en utilisant la chromatographie à échange d'anions et la chromatographie à charbon actif et à cristalliser le cristal au moyen d'un solvant organique hydrophile.'invention concerne aussi un procédé de fabrication de U2P4 ou d'un sel de celui-ci, qui consiste à fournir du UMP, utilisé comme substance de départ, et à utiliser DPC et PPi. Le procédé est caractérisé en ce que l'on applique au moins un traitement parmi les suivants: (a) au stade de réaction entre UMP-DPP et un sel alcalin PPi-organique, ajouter UMP-DPP à plusieurs reprises (b) au stade de réaction entre UMP-DPP et un sel alcalin PPi-organique, effectuer la réaction en présence d'une base et (c) après la réaction de synthèse d'U2P4 soumettre le produit de la réaction à un traitement alcalin.

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