Process for preparing purine nucleosides

A process for the preparation of a β-nucleoside of the formula:

• 20
• wherein R2 and R3 are independently hydroxy protecting groups, comprising reacting an α-arabinofuranosyl of the formula:
• 21
• wherein R2 and R3 are as defined above and R4 is a leaving group selected from the group consisting of halogen, alkylsulfonyloxy, and arylsulfonyloxy, with 2-chloroadeinine, wherein the C-6 exocyclic amino group of said 2-chloroadenine is not protected, in the presence of base and a solvent, wherein there is no substantial production of adducts formed by addition of said α-arabinofuranosyl with said C-6 exocyclic amino group of said 2-chloroadenine.

A process for the stereoselective preparation of a 2′-deoxy-β-nucleoside of the formula:

• 24
• wherein, R2 and R3 are independently hydroxy protecting groups, and R5 is a halogen or —NH2, comprising reacting a 2-deoxy-α-arabinofuranosyl derivative of the formula:
• 25
• wherein R7 is a halogen and R2 and R3 are as defined above, with an adenine derivative salt of the formula:
• 26
• wherein R5 is as defined above and the C-6 exocyclic amino group of said adenine derivative salt is not protected, in the presence of a solvent, wherein said 2′-deoxy-β-nucleoside is produced in a molar ratio of at least 10:1 relative to the 2′-deoxy-α-nucleoside anomer represented by the formula:
• 27

A process for the stereoselective preparation of a 2′-deoxy-β-nucleoside of the formula:

• 31
• wherein, R2 and R3 are independently hydroxy protecting groups, comprising reacting a 2-deoxy-α-arabinofuranosyl derivative of the formula:
• 32
• wherein R2 and R3 are as defined above, with an adenine derivative salt of the formula:
• 33
• wherein the C-6 exocyclic amino group of said adenine derivative salt is not protected, in the presence of a solvent, wherein said 2′-deoxy-β-nucleoside is produced in a molar ratio of at least 10:1 relative to the 2′-deoxy-α-nucleoside anomer represented by the formula:
• 34

A process for the preparation of a composition comprising 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine comprising:

• (1) reacting 3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl bromide with a 2-chloroadeinine potassium salt of the formula:
• 38
• wherein the exocyclic amino group of said 2-chloroadenine potassium salt is not protected, in the presence of a solvent to form 2-chloro-9-(3′,5′-O-dibenzoyl-2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine;
• (2) deprotecting said 2-chloro-9-(3′,5′-O-dibenzoyl-2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)adenine to from 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine;
• and
• (3) isolating said 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine to form a composition comprising 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) adenine.