Nucleoside phosphoramidates

Abstract

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

1 .- 70 . (canceled) 
     
     
         71 . A tablet comprising crystalline (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate represented by the formula Sp-4: 
       
         
           
           
               
               
           
         
         having XRPD 2θ-reflections (±0.2°) at 6.1 and 12.7. 
       
     
     
         72 . The tablet of  claim 71 , wherein the crystalline Sp-4 has further XRPD 2θ-reflections (±0.2°) at 8.2, 10.4, 17.2, 17.7, 18.0, 18.8, 19.4, 19.8, 20.1, 20.8, 21.8 and 23. 
     
     
         73 . A tablet comprising Sp-4: 
       
         
           
           
               
               
           
         
         wherein at least 70% of the Sp-4 is the crystalline Sp-4 of  claim 71 . 
       
     
     
         74 . The tablet of  claim 73 , wherein at least 80% of the Sp-4 is the crystalline Sp-4 of  claim 71 . 
     
     
         75 . The tablet of  claim 73 , wherein at least 90% of the Sp-4 is the crystalline Sp-4 of  claim 71 . 
     
     
         76 . A method of treating a hepatitis C virus infection comprising administering the tablet of  claim 71  to a subject in need thereof. 
     
     
         77 . A method of treating a hepatitis C virus infection comprising administering the tablet of  claim 71  in combination with another antiviral agent to a subject in need thereof. 
     
     
         78 . The method of  claim 77 , wherein the another antiviral agent is a HCV NS3 protease inhibitor. 
     
     
         79 . The method of  claim 77 , wherein the another antiviral agent is a HCV NS5A inhibitor. 
     
     
         80 . The method of  claim 77 , wherein the another antiviral agent is a HCV NS3 protease inhibitor and a HCV NS5A inhibitor.