Process for preparing purine nucleosides

Abstract

The present invention for the stereoselective preparation of 2-deoxy-β-D-adenine nucleosides wherein a blocked 2-deoxy-α-D-arabinofuranosyl halide is coupled with the salt of an adenine derivative.

1 - 30 . (canceled) 
     
     
         31 . The compound 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine, wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is greater than about 10:1. 
     
     
         32 . The compound of  claim 31 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is greater than about 15:1. 
     
     
         33 . The compound of  claim 31 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is greater than about 20:1. 
     
     
         34 . The compound of  claim 31 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is greater than about 40:1. 
     
     
         35 . The compound of  claim 31 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is greater than about 60:1. 
     
     
         36 . The compound of  claim 31 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is 10.7:1. 
     
     
         37 . The compound of  claim 31  substantially free of 2-chloroadenine. 
     
     
         38 . The compound of  claim 37  having a purity of at least 98.1% by HPLC (a.u.c.). 
     
     
         39 . The compound of  claim 37 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is 11.9:1. 
     
     
         40 . The compound of  claim 31 , wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is 19:1. 
     
     
         41 . The compound of  claim 40  having a purity of at least 88% by HPLC (a.u.c.). 
     
     
         42 . The compound of  claim 31 , wherein the anomeric ratio of the 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is 19.4:1. 
     
     
         43 . The compound of  claim 42  having a purity of at least 90% by HPLC (a.u.c.). 
     
     
         44 . The compound 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine, wherein the anomeric ratio of 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(3,5-O-dibenzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl)adenine is between 6.73:1 and 22.1:1. 
     
     
         45 . The compound 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)adenine, wherein the anomeric ratio of 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(2′-deoxy-2′-fluoro-α-D-arabinofuranosyl)adenine as measured by high pressure liquid chromatography and spectrophotometric analysis, is at least about 99:1. 
     
     
         46 . The compound 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)adenine having a purity of about 99.14% by HPLC (a.u.c.). 
     
     
         47 . The compound of  claim 46 , wherein the compound is substantially free of 2-chloro-9-(2′-deoxy-2′-fluoro-α-D-arabinofuranosyl)adenine. 
     
     
         48 . The compound 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)adenine, wherein the anomeric ratio of 2-chloro-9-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)adenine to 2-chloro-9-(2′-deoxy-2′-fluoro-α-D-arabinofuranosyl)adenine between about 126:1 and about 09:1.