Crystalline Salts of a Potent HCV Inhibitor

Abstract

This invention relates to novel tris(hydroxymethyl)aminomethane, choline and N-methyl-D-glucamine salt forms of the following Compound (1) and methods for the preparation thereof, pharmaceutical compositions thereof, and their use in the treatment of Hepatitis C Viral (HCV) infection:

1 . A crystalline choline salt of the compound of the following formula (1): 
       
         
           
           
               
               
           
         
       
     
     
         2 . The crystalline salt according to  claim 1 , having an X-ray powder diffraction pattern comprising a peak at 7.5 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         3 . The crystalline salt according to  claim 1 , having an X-ray powder diffraction pattern comprising peaks at 7.5, 14.9 and 17.5 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         4 . The crystalline salt according to  claim 1 , having an X-ray powder diffraction pattern comprising peaks at 7.5, 14.9, 17.5, 22.1 and 24.3 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         5 . The crystalline salt according to  claim 1 , having an X-ray powder diffraction pattern comprising peaks at 7.5, 14.2, 14.9, 17.5, 21.8, 22.1, 22.7 and 24.3 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         6 . The crystalline salt according to  claim 1 , that has a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 175.1, 137.6 and 27.2 ppm (±0.2 ppm) 
     
     
         7 . The crystalline salt according to  claim 1 , that has a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 175.1, 172.6, 172.2, 147.8, 147.1, 137.6 and 27.2 ppm (all ±0.2 ppm). 
     
     
         8 . The crystalline salt according to  claim 1 , that has a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 175.1, 172.6, 172.2, 170.2, 154.9, 149.5, 147.8, 147.1, 137.6, 27.2 and 15.7 ppm (all ±0.2 ppm). 
     
     
         9 . The crystalline salt according to  claim 1 , that has an X-ray powder diffraction pattern comprising a peak at 7.5 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation and a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 175.1, 137.6 and 27.2 ppm (±0.2 ppm). 
     
     
         10 . A crystalline N-methyl-D-glucamine salt of the compound of the following formula (1): 
       
         
           
           
               
               
           
         
       
     
     
         11 . The crystalline salt according to  claim 10 , having an X-ray powder diffraction pattern comprising a peak at 4.4 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         12 . The crystalline salt according to  claim 10 , having an X-ray powder diffraction pattern comprising peaks at 2.5, 4.4 and 5.1 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         13 . The crystalline salt according to  claim 10 , having an X-ray powder diffraction pattern comprising peaks at 2.5, 4.4, 5.1, 11.7 and 15.9 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         14 . The crystalline salt according to  claim 10 , having an X-ray powder diffraction pattern comprising peaks at 2.5, 4.4, 5.1, 11.7, 15.5, 15.9 and 20.9 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation. 
     
     
         15 . The crystalline salt according to  claim 10 , that has a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 178.4, 138.0 and 27.0 ppm (±0.2 ppm). 
     
     
         16 . The crystalline salt according to  claim 10 , that has a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 178.4, 175.6, 159.8, 154.2, 151.2, 138.0 and 27.0 ppm (all ±0.2 ppm). 
     
     
         17 . The crystalline salt according to  claim 10 , that has a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 178.4, 175.6, 173.4, 172.3, 159.8, 154.2, 151.2, 138.0, 27.0, 24.7 and 20.8 ppm (all ±0.2 ppm). 
     
     
         18 . The crystalline salt according to  claim 10 , that has an X-ray powder diffraction pattern comprising a peak at 4.4 degrees 2θ (±0.2 degrees 2θ) when measured using CuKα radiation and a  13 C solid state NMR spectrum comprising peaks at chemical shifts of 178.4, 138.0 and 27.0 ppm (±0.2 ppm). 
     
     
         19 . A pharmaceutical composition comprising a salt according to  claim 1 , and at least one pharmaceutically acceptable carrier or diluent. 
     
     
         20 . A pharmaceutical composition comprising a salt according to  claim 10 , and at least one pharmaceutically acceptable carrier or diluent.