Solid forms of an antiviral compound

Abstract

Amorphous and crystalline solid forms of the anti-HCV compound (1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the amorphous and crystalline forms.

We claim: 
     
         1 . Amorphous 1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester, characterized by a modulated differential scanning calorimetry (mDSC) curve that comprises a glass transition temperature of about 160° C. 
     
     
         2 . Amorphous Compound I according to  claim 1 , wherein the mDSC curve is substantially as shown in  FIG. 35 . 
     
     
         3 . Amorphous Compound I according to  claim 1 , characterized by  13 C-solid state NMR (ssNMR) spectra substantially as shown by top curve in  FIG. 34 . 
     
     
         4 . Amorphous Compound I according to  claim 1 , characterized by Fourier-transformed Raman spectra that comprises peaks at 939 and 1552 cm −1 . 
     
     
         5 . Amorphous Compound I according to  claim 4 , wherein the Fourier-transformed Raman spectra is substantially as shown in  FIG. 36 . 
     
     
         6 . A method for treating a subject suffering from hepatitis C virus (HCV), comprising administering to the subject a therapeutically effective amount of amorphous Compound I according to  claim 1 .