Anti-Viral Compounds

Abstract

Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

What is claimed is: 
     
         1 . A compound of Formula I, or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 X is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A ; 
 L 1  and L 2  are each independently selected from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; 
 L 3  is bond or -L S -K-L S ′-, wherein K is selected from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O)—, —N(R B )C(O)N(R B ′)—, N(R B )SO 2 N(R B ′)—, or —N(R B )S(O)N(R B ′)—; 
 A and B are each independently C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and are each independently optionally substituted with one or more R A ; 
 D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A ; 
 Y is selected from -T′-C(R 1 R 2 )N(R 5 )-T-R D  or -T′-C(R 3 R 4 )C(R 6 R 7 )-T-R D ; 
 R 1  and R 2  are each independently R C , and R 5  is R B ; or R 1  is R C , and R 2  and R 5 , taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more R A ; 
 R 3 , R 4 , R 6 , and R 7  are each independently R C ; or R 3  and R 6  are each independently R C , and R 4  and R 7 , taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more R A ; 
 Z is selected from -T′-C(R 8 R 9 )N(R 12 )-T-R D  or -T′-C(R 10 R 11 )C(R 13 R 14 )-T-R D ; 
 R 8  and R 9  are each independently R C , and R 12  is R B ; or R 8  is R C , and R 9  and R 12 , taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more R A ; 
 R 10 , R 11 , R 13 , and R 14  are each independently R C ; or R 10  and R 13  are each independently R C , and R 11  and R 14 , taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more R A ; 
 T and T′ are each independently selected at each occurrence from bond, -L S -, -L S -M-L S ′-, or -L S -M-L S ′-M′-L S ″-, wherein M and M′ are each independently selected at each occurrence from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, —S(O) 2 N(R B )—, —C(O)N(R B )C(O)—, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, —N(R B )S(O)N(R B ′)—, C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and wherein said C 3 -C 12 carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more R A ; 
 R D  is each independently selected at each occurrence from hydrogen or R A ; 
 R A  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E , wherein two adjacent R A , taken together with the atoms to which they are attached and any atoms between the atoms to which they are attached, can optionally form carbocycle or heterocycle; 
 R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R B  or R B  is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R C  is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R C  is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S , —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′) or —C(O)N(R S )C(O)—R S ′; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 3 -C 6 carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , C(O)N(R S R S ′) or —N(R S )C(O)R S ; or C 3 -C 6 carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 L S , L S ′ and L S ″ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; and 
 R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R S , R S ′ or R S ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl. 
 
     
     
         2 . The compound or salt of  claim 1 , wherein:
 A is selected from C 5 -C 6 carbocycle, 5- to 6-membered heterocycle,   
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A ;
 B is selected from C 5 -C 6 carbocycle, 5- to 6-membered heterocycle, 
 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A ;
 D is selected from C 5 -C 6 carbocycle or 5- to 6-membered heterocycle, and is optionally substituted with one or more R A ; or D is hydrogen or R A ; 
 Z 1  is independently selected at each occurrence from O, S, NH or CH 2 ; 
 Z 2  is independently selected at each occurrence from N or CH; 
 Z 3  is independently selected at each occurrence from N or CH; 
 Z 4  is independently selected at each occurrence from O, S, NH or CH 2 ; and 
 W 1 , W 2 , W 3 , W 4 , W 5  and W 6  are each independently selected at each occurrence from CH or N. 
 
     
     
         3 . The compound or salt of  claim 1 , wherein:
 A is selected from C 5 -C 6 carbocycle, 5- to 6-membered heterocycle,   
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A ;
 B is selected from C 5 -C 6 carbocycle, 5- to 6-membered heterocycle, 
 
       
         
           
           
               
               
           
         
       
       and is optionally substituted with one or more R A ;
 D is selected from C 5 -C 6 carbocycle or 5- to 6-membered heterocycle, and is optionally substituted with one or more R A ; or D is hydrogen or R A ; 
 Z 1  is independently selected at each occurrence from O, S, NH or CH 2 ; 
 Z 2  is independently selected at each occurrence from N or CH; and 
 W 1 , W 2 , W 3 , W 4 , W 5  and W 6  are each independently selected at each occurrence from CH or N. 
 
     
     
         4 . The compound or salt of  claim 1 , wherein:
 A and B are each independently C 5 -C 6 carbocycle or 5- to 6-membered heterocycle, and are each independently optionally substituted with one or more R A ;   D is selected from C 5 -C 6 carbocycle or 5- to 6-membered heterocycle, and is optionally substituted with one or more R A ; and   X is   
       
         
           
           
               
               
           
         
       
       wherein X 3  is N and is directly linked to -L 3 -D, and X is optionally substituted with one or more R A , and two adjacent R A  on X, taken together with the ring atoms to which they are attached, optionally form a 5- to 6-membered carbocycle or heterocycle. 
     
     
         5 . A compound of Formula I, or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
       
       wherein:
 X is 
 
       
         
           
           
               
               
           
         
       
       wherein the nitrogen ring atom is directly linked to -L 3 -D, and wherein X is optionally substituted with one or more R A ;
 L 1 , L 2  and L 3  are bond; 
 A and B are each independently 
 
       
         
           
           
               
               
           
         
       
       and are each independently optionally substituted with one or more R A ;
 D is C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and is optionally substituted with one or more R A ; 
 Y is -G-C(R 1 R 2 )N(R 5 )-T-R D , -G-C(R 3 R 4 )C(R 6 R 7 )-T-R D , —N(R B )C(O)C(R 1 R 2 )N(R 5 )-T-R D , or —N(R B )C(O)C(R 3 R 4 )C(R 6 R 7 )-T-R D ; 
 Z is -G-C(R 8 R 9 )N(R 12 )-T-R D , -G-C(R 10 R 11 )C(R 13 R 14 )-T-R D , —N(R B )C(O)C(R 8 R 9 )N(R 12 )-T-R D , or —N(R B )C(O)C(R 10 R 11 )C(R 13 R 14 )-T-R D ; 
 R 1  is R C , and R 2  and R 5 , taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more R A ; 
 R 3  and R 6  are each independently R C , and R 4  and R 7 , taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more R A ; 
 R 8  is R C , and R 9  and R 12 , taken together with the atoms to which they are attached, form a 3- to 12-membered heterocycle which is optionally substituted with one or more R A ; 
 R 10  and R 13  are each independently R C , and R 11  and R 14 , taken together with the atoms to which they are attached, form a 3- to 12-membered carbocycle or heterocycle which is optionally substituted with one or more R A ; 
 G is each independently C 5 -C 6 carbocycle or 5- to 6-membered heterocycle, and is each independently optionally substituted with one or more R A ; 
 T is each independently selected at each occurrence from bond, -L S -, -L S -M-L S ′-, or -L S -M-L S ′-M′-L S ″-, wherein M and M′ are each independently selected at each occurrence from bond, —O—, —S—, —N(R B )—, —C(O)—, —S(O) 2 —, —S(O)—, —OS(O)—, —OS(O) 2 —, —S(O) 2 O—, —S(O)O—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(O)N(R B )—, —N(R B )C(O)—, —N(R B )C(O)O—, —OC(O)N(R B )—, —N(R B )S(O)—, —N(R B )S(O) 2 —, —S(O)N(R B )—, S(O) 2 (O)N—, (R B )C(O)—, —N(R B )C(O)N(R B ′)—, —N(R B )SO 2 N(R B ′)—, N(R B )S(O)N(R B ′)—, C 3 -C 12 carbocycle or 3- to 12-membered heterocycle, and wherein said C 3 -C 12 carbocycle and 3- to 12-membered heterocycle are each independently optionally substituted at each occurrence with one or more R A ; 
 R D  is each independently selected at each occurrence from hydrogen or R A ; 
 R A  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, or -L S -R E ; 
 R B  and R B ′ are each independently selected at each occurrence from hydrogen; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R B  or R B  is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R C  is independently selected at each occurrence from hydrogen, halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R C  is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R E  is independently selected at each occurrence from —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , —C(O)N(R S R S ′), —N(R S )C(O)R S ′, —N(R S )C(O)N(R S ′R S ″), —N(R S )SO 2 R S ′, —SO 2 N(R S R S ′), —N(R S )SO 2 N(R S ′R S ″), —N(R S )S(O)N(R S ′R S ″), —OS(O)—R S , —OS(O) 2 —R S , —S(O) 2 OR S , —S(O)OR S , —OC(O)OR S , —N(R S )C(O)OR S , —OC(O)N(R S R S ′), —N(R S )S(O)—R S ′, —S(O)N(R S R S ′) or —C(O)N(R S )C(O)—R S ′; or C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl or cyano; or C 3 -C 6 carbocycle or 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 R L  is independently selected at each occurrence from halogen, nitro, oxo, phosphonoxy, phosphono, thioxo, cyano, —O—R S , —S—R S , —C(O)R S , —OC(O)R S , —C(O)OR S , —N(R S R S ′), —S(O)R S , —SO 2 R S , C(O)N(R S R S ′) or —N(R S )C(O)R S ; or C 3 -C 6 carbocycle 3- to 6-membered heterocycle, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl; 
 L S , L S ′ and L S ″ are each independently selected at each occurrence from bond; or C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene, each of which is independently optionally substituted at each occurrence with one or more R L ; and 
 R S , R S ′ and R S ″ are each independently selected at each occurrence from hydrogen; C 1 -C 6 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl, each of which is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano or 3- to 6-membered carbocycle or heterocycle; or 3- to 6-membered carbocycle or heterocycle; wherein each 3- to 6-membered carbocycle or heterocycle in R S , R S ′ or R S ′ is independently optionally substituted at each occurrence with one or more substituents selected from halogen, hydroxy, mercapto, amino, carboxy, nitro, oxo, phosphonoxy, phosphono, thioxo, formyl, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl or C 2 -C 6 haloalkynyl. 
 
     
     
         6 . The compound or salt of  claim 5 , wherein:
 T is independently selected at each occurrence from —C(O)-L S ′-M′-L S ″- or —N(R B )C(O)-L S ′-M′-L S ″-; and   L S ′ is each independently C 1 -C 6 alkylene, and is independently optionally substituted at each occurrence with one or more R L .   
     
     
         7 . The compound or salt of  claim 5 , wherein:
 Y is —N(R B )C(O)C(R 1 R 2 )N(R 5 )-T-R D ;   Z is —N(R B )C(O)C(R 8 R 9 )N(R 12 )-T-R D ;   T is independently selected at each occurrence from —C(O)-L S ′-M′-L S ″-; and   D is C 5 -C 6 carbocycle, 5- to 6-membered heterocycle, or 6- to 10-membered bicycles, and is substituted with one or more R A .   
     
     
         8 . The compound or salt of  claim 7 , wherein T is independently selected at each occurrence from —C(O)-L S ′—N(R B )C(O)-L S ″- or —C(O)-L S ′—N(R B )C(O)O-L S ″-; and R 2  and R 5 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A ; and R 9  and R 12 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A . 
     
     
         9 . The compound or salt of  claim 5 , wherein:
 Y is -G-C(R 1 R 2 )N(R 5 )-T-R D ;   Z is -G-C(R 8 R 9 )N(R 12 )-T-R D ;   G is each independently   
       
         
           
           
               
               
           
         
       
       and is each independently optionally substituted with one or more R A ;
 T is independently selected at each occurrence from —C(O)-L S ′-M′-L S ″-; and 
 D is C 5 -C 6 carbocycle, 5- to 6-membered heterocycle, or 6- to 10-membered bicycles, and is substituted with one or more R A . 
 
     
     
         10 . The compound or salt of  claim 9 , wherein T is independently selected at each occurrence from —C(O)-L S ′—N(R B )C(O)-L S ″- or —C(O)-L S ′—N(R B )C(O)O-L S ″-; and R 2  and R 5 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A ; and R 9  and R 12 , taken together with the atoms to which they are attached, form 
       
         
           
           
               
               
           
         
       
       which is optionally substituted with one or more R A . 
     
     
         11 . A process of making an HCV inhibitor according to a scheme selected from Scheme I to Scheme XXV. 
     
     
         12 . A process of making an HCV inhibitor according to the following scheme as defined in the specification: