Preparation process of an antiviral drug (entecavir) and intermediates thereof

A process for the preparation of entecavir of formula (I), or a pharmaceutically acceptable salt thereof,

• which comprises submitting a compound of formula (VIII) to a double esterification and to a catalytic radicalary cyclization using titanocene dichloride as catalyst in the presence of Mn/2,4,6-collidine HCl or Zn/2,4,6-collidine/trimethylsilyl chloride, yielding to a compound of formula (V),
• wherein:
• either a compound of formula (VIII) is submitted to a first esterification reaction, yielding to a compound of formula (VII);
• then to the catalytic radicalary cyclization to yield a compound of formula (VIa);
• followed by a second esterification reaction, to yield a compound of formula (V);
• or, alternatively,
• the compound of formula (VIII) is submitted first to the catalytic radicalary cyclization, to yield a compound of formula (VIb);
• and then to a esterification reaction, to yield a compound of formula (V);
• and
• wherein:
• R1 and R2 are radicals independently selected from the group consisting of (C1-C6)-alkyl, phenyl, and phenyl substituted by a radical selected from the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy, halogen, and nitro.