Method of producing 2'-deoxy-5-azacytidine (decitabine)

Abstract

The invention relates to a method of producing 2'-deoxy-5-azacytidine (Decitabine) by providing a compound of formula (I) shown in the description, wherein R is a removable substituent known per se; and R1 is a removable substituent; further providing a silylated base of formula (II) shown in the description, wherein R2 is a protecting group, preferably a trimethylsilyl TMS )-residue; reacting the compound of formula (I) and the compound of formula (II) together in a suitable anhydrous solvent and in the presence of a suitable catalyst; and removing the substituents R from the compound obtained in order to obtain the compound 2'-deoxy-5-azacytidine (Decitabine), characterized in that said catalyst is selected from the group comprising a salt of an aliphatic sulphonic acid or a salt of a strong inorganic acid.

Description

technical field The present invention relates to a process for the production of 2'-deoxy-5-azacytidine (decitabine) by reacting a glycoside donor with a selected silylated base in the presence of a selected catalyst, The glycoside donor is preferably a 1-halogenated derivative of blocked mono-saccharide, or an imidate, preferably a trichloromethyl derivative, or a thioalkyl derivative. Background technique Decitabine is a nucleoside and is a known pharmaceutically active compound. It is known from US 3,817,980 that by silylation of the corresponding nucleoside base and combining the silylated base with a glycoside donor, preferably a 1-halogenated derivative of a capped monosaccharide, on a selected catalyst The reaction is carried out in the presence of nucleosides. The catalyst used is selected from e.g. SnCl 4 、TiCl 4 , ZnCl 2 , BF 3 - etherate (BF 3 -etherate), AlCl 3 and SbCl 5 . The main disadvantage is that these catalysts are prone to hydrolysis, producing...

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