Patent ID: 8212021

Claim:
A process for the preparation of a 5-azacytosine nucleoside compound of formula I: wherein R 1 is hydrogen, hydroxy or halogen; R 2 is hydrogen or halogen comprising: a. reacting 5-azacytosine with a silylating agent to produce a reaction mixture containing a silylated 5-azacytosine of formula II: wherein each of R 3 is independently optionally substituted C 1 -C 20 alkyl group or aryl group; b. coupling the silylated 5-azacytosine of formula II with a protected D-ribofuranose of formula III: wherein R 1 ′ is hydrogen, halogen or OR 4 ; R 4 represents a hydroxyl-protecting group; in a first organic solvent and in the presence of a sulfonic acid catalyst to obtain a solution of a protected 5-azacytosine nucleoside of formula IV: wherein each of R 5 and R 6 is independently hydrogen or Si(R 3 ) 3 , R 3 is an optionally substituted C 1 -C 20 alkyl or aryl group, and R 1 ′ and R 2 are as defined above; and c. converting the protected 5-azacytosine nucleoside of formula (IV) to the 5-azacytosine nucleoside of formula (I); wherein prior to the step of b), the silylated 5-azacytosine compound is isolated in a solid form from the reaction mixture of the step a).