Aminopyrimidines useful as kinase inhibitors

Abstract

The present invention relates to compounds useful as inhibitors of Aurora protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

We claim: 
     
         1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         Ht is 
       
       
         
           
           
               
               
           
         
         R 2  is H, C 1-3 alkyl, or cyclopropyl; 
         R 2′  is H; 
         Q is —S—; 
         R X  is H or F; 
         R Y  is 
       
       
         
           
           
               
               
           
         
         each J is independently F or C 1-6 alkyl; 
         n is 1; 
         R 4  is H, C 1-6 -alkyl, C 3-8 cycloaliphatic, or a 4-8 membered heterocyclyl containing 1-2 heteroatoms selected from O, N, or S; wherein said alkyl, cycloaliphatic or heterocyclyl is optionally and independently substituted with 0-6 occurrences of C 1-6 alkyl, —O—(C 1-6 alkyl), NH 2 , OH, ═O, halo, CN, or NO 2 ; 
         R 1  is a 6:5 heteroaryl ring system containing 1-5 heteroatoms selected from O, N, and S and optionally substituted with 0-4 J D ; 
         each J D  is independently C 1-6 alkyl, —O—(C 1-6 -alkyl), halo, or oxo wherein each C 1-6 alkyl is optionally substituted with 0-6 fluoro. 
       
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The compound of  claim 1 , wherein R 2  is C 1-3  alkyl or cyclopropyl. 
     
     
         5 . The compound of  claim 1 , wherein R 2′  is H. 
     
     
         6 . The compound of  claim 1 , wherein R X  is H. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . The compound of  claim 1 , wherein R 4  is H, C 1-6 alkyl,
 C 3-8 cycloaliphatic, or a 4-8 membered heterocyclyl containing 1-2 heteroatoms selected from O or N; wherein said alkyl, cycloaliphatic or heterocyclyl is optionally and independently substituted with 0-6 occurrences of C 1-6 alkyl, —O—(C 1-6 -alkyl), NH 2 , OH, ═O, halo, CN, or NO 2 .   
     
     
         10 . The compound of  claim 9 , wherein R 4  is C 1-6 alkyl, C 3-8  cycloaliphatic, or a 4-8 membered heterocyclyl containing 1-2 heteroatoms selected from O or N; wherein said alkyl, cycloaliphatic or heterocyclyl is optionally and independently substituted with 0-6 occurrences of C 1-6 alkyl, —O—(C 1-6 alkyl), NH 2 , OH, ═O, halo, CN, or NO 2 . 
     
     
         11 . The compound of  claim 10 , wherein R 4  is a 4-8 membered heterocyclyl containing 1-2 heteroatoms selected from O or N. 
     
     
         12 . The compound of  claim 10 , wherein R 4  is a 5-6 membered heterocyclyl containing 1-2 heteroatoms selected from O or N. 
     
     
         13 . The compound of  claim 10 , wherein R 4  is C 1-6 alkyl. 
     
     
         14 . The compound of  claim 10 , wherein R 4  is C 3-6  cycloalkyl. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . The compound of  claim 1 , wherein said 6:5 ring system contains 2 nitrogen atoms. 
     
     
         20 . The compound of  claim 19 , wherein R 1  is a benzimidazole, indazole, or imidazopyridine ring. 
     
     
         21 . The compound of  claim 20 , wherein R 1  is a benzimidazole ring. 
     
     
         22 - 41 . (canceled) 
     
     
         42 . A composition a compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein the variables are as defined according to any one of  claims 1 - 41 . 
       
     
     
         43 - 52 . (canceled) 
     
     
         53 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         Ht is 
       
       
         
           
           
               
               
           
         
         R 2  is H, C 1-3 alkyl, or cyclopropyl; 
         R 2′  is H; 
         Q is —S—; 
         Rx is H or F; 
         R Y  is 
       
       
         
           
           
               
               
           
         
         each J is independently F or C 1-6 alkyl; 
         n is 1; 
         R 4  is H, C 1-6 alkyl, C 3-8  cycloaliphatic, or a 4-8 membered heterocyclyl containing 1-2 heteroatoms selected from O, N, or S; wherein said alkyl, cycloaliphatic or heterocyclyl is optionally and independently substituted with 0-6 occurrences of C 1-6 alkyl, —O—(C 1-6 alkyl), NH 2 , OH, ═O, halo, CN, or NO 2 ; 
         R 1  is a 6:6 heteroaryl ring system containing 1-5 heteroatoms selected from O, N, and S and optionally substituted with 0-4 J D ; 
         each J D  is independently C 1-6 alkyl, —O—(C 1-6 -alkyl), halo, or oxo wherein each C 1-6 alkyl is optionally substituted with 0-6 fluoro. 
       
     
     
         54 . The compound of  claim 53 , wherein R 1  is quinoline.