Convergent processes for preparing macrolide antibacterial agents

Abstract

The invention described herein relates to processes for preparing ketolide antibacterial agents. In particular, the invention relates to intermediates and processes for preparing ketolides that include a 1,2,3-triazole substituted side chain.

1 - 25 . (canceled) 
     
     
         26 . A composition comprising solithromycin that is substantially free of 
       
         
           
           
               
               
           
         
       
       wherein A-B is (CH 2 ) 4 . 
     
     
         27 . A compound of the formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, or C(O)NHS(O) 2 ; 
 B is saturated C 0 C 10 ; or B is unsaturated C 2 C 10 ; or 
 AB taken together is alkylene, alkenylene, cycloalkylene, or arylene; 
 C is hydrogen, halogen, hydroxy, acyl, acyloxy, sulfonyl, ureyl, and carbamoyl, and alkyl, alkoxy, heteroalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl, each of which is optionally substituted; and 
 R 100  is hydrogen or a hydroxyl protecting group. 
 
     
     
         28 . The compound of  claim 27  wherein C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted. 
     
     
         29 . The compound of  claim 27  wherein A is CH 2 . 
     
     
         30 . The compound of  claim 27  wherein B is (CH 2 ) n , and n is an integer from 2-6. 
     
     
         31 . The compound of  claim 27  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         32 . The compound of  claim 27  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         33 . The compound of  claim 32  wherein R 100  is hydrogen. 
     
     
         34 . An intermediate of the formulae 
       
         
           
           
               
               
           
         
       
       wherein:
 A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, or C(O)NHS(O) 2 ; 
 B is saturated C 0 C 10 ; or B is unsaturated C 2 C 10 ; or 
 AB taken together is alkylene, alkenylene, cycloalkylene, or arylene; 
 C is hydrogen, halogen, hydroxy, acyl, acyloxy, sulfonyl, ureyl, and carbamoyl, and alkyl, alkoxy, heteroalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl, each of which is optionally substituted; or C is C P , where C P  is a protected form of C; 
 R 100  is hydrogen or a hydroxyl protecting group; and 
 N P  is NH 2  or protected amino. 
 
     
     
         35 . The intermediate of  claim 34  wherein C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted. 
     
     
         36 . The intermediate of  claim 34  wherein A is CH 2 . 
     
     
         37 . The intermediate of  claim 34  wherein B is (CH 2 ) n , and n is an integer from 2-6. 
     
     
         38 . The intermediate of  claim 34  wherein B is (CH 2 ) n , and n is 2, 3, or 
     
     
         4 . 
     
     
         39 . The intermediate of  claim 34  wherein R 100  is acyl. 
     
     
         40 . The intermediate of  claim 34  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         41 . The intermediate of  claim 34  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         42 . The intermediate of  claim 34  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         43 . The intermediate of  claim 34  of the formula 
       
         
           
           
               
               
           
         
       
     
     
         44 . The intermediate of  claim 34  of the formula