Synthesis of purine nucleosides
A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.
1. A compound of formula IV:
or a salt thereof, wherein:
R 5 is H or N 3 ;
R 6 is CH 3 ;
R 11 is a protecting group; and
X is F.
2. A compound of formula V:
or a salt thereof, wherein:
R 5 is N 3 ;
R 6 is CH 3 ;
R 11 is a protecting group;
X is F; and
X′ is Cl, Br, or I.
3. The compound of claim 1 , wherein R 5 is H.
4. A process for preparing a compound of formula IV, wherein said process comprises:
(a) stereoselective reduction of a compound of formula III using a hydride reducing agent to provide a mixture comprising a compound of formula IV and a compound of formula IV-α:
and
(b) crystallizing the compound of formula IV from the mixture comprising the compounds of formula IV and formula IV-α:
wherein R 11 is a protecting group.