Substituted oxopyridine derivatives

Abstract

The invention relates to substituted oxopyridine derivatives and to processes for their preparation, and also to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular cardiovascular disorders, preferably thrombotic or thromboembolic disorders, and oedemas, and also ophthalmic disorders.

1 . A process for preparing a compound of the formula (I) or a salt thereof 
       
         
           
           
               
               
           
         
         wherein 
         R 1  represents a group of the formula 
       
       
         
           
           
               
               
           
         
         
           wherein * is the point of attachment to the oxopyridine ring, 
           R 6  represents chlorine, 
           R 7  represents 1,2,3-triazolyl,
 wherein the 1,2,3-triazolyl is substituted by a substituent selected from the group consisting of chlorine, difluoromethyl and trifluoromethyl, 
 
           R 8  represents hydrogen, 
         
         R 2  represents methoxy, 
         R 3  represents methyl, ethyl or n-propyl, 
         R 4  represents hydrogen, 
         R 5  represents a group of the formula 
       
       
         
           
           
               
               
           
         
         
           wherein # is the point of attachment to the nitrogen atom, 
           R 14  represents fluorine, 
           R 15  represents hydrogen, 
         
         R 16  represents hydrogen,
 comprising reacting a compound of the formula 
 
       
       
         
           
           
               
               
           
         
         
           with a compound of the formula 
         
       
       
         
           
           
               
               
           
         
         
           in the presence of a dehydrating reagent to give a compound of the formula (I). 
         
       
     
     
         2 . The process according to  claim 1 , wherein, in the compound of formula (I) in the composition, R 3  represents ethyl and R 7  is 1,2,3-triazole substituted by chlorine or trifluoromethyl. 
     
     
         3 . The process according to  claim 1 , wherein the compound of formula (I) in the composition is 4-({(2S)-2-[4-{5-Chloro-2-[4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]phenyl}-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2-fluorobenzamide (enantiomer 2) of the formula 
       
         
           
           
               
               
           
         
       
     
     
         4 . The process according to  claim 1 , wherein the compound of formula (I) in the composition is 4-{[(2S)-2-{4-[5-Chloro-2-(4-chloro-1H-1,2,3-triazol-1-yl)phenyl]-5-methoxy-2-oxopyridin-1(2H)-yl}butanoyl]amino}-2-fluorobenzamide (enantiomer 2) of the formula 
       
         
           
           
               
               
           
         
       
     
     
         5 . A process for preparing a compound of the formula (I) or a salt thereof of the formula 
       
         
           
           
               
               
           
         
         wherein 
         R 1  represents a group of the formula 
       
       
         
           
           
               
               
           
         
         
           wherein * is the point of attachment to the oxopyridine ring, 
           R 6  represents chlorine, 
           R 7  represents 1,2,3-triazolyl,
 wherein the 1,2,3-triazolyl is substituted by a substituent selected from the group consisting of chlorine, difluoromethyl and trifluoromethyl, 
 
           R 8  represents hydrogen, 
         
         R 2  represents methoxy, 
         R 3  represents methyl, ethyl or n-propyl, 
         R 4  represents hydrogen, 
         R 5  represents a group of the formula 
       
       
         
           
           
               
               
           
         
         
           wherein # is the point of attachment to the nitrogen atom, 
           R 14  represents fluorine, 
           R 15  represents hydrogen, 
         
         R 16  represents hydrogen, 
         comprising reacting a compound of the formula (V) 
       
       
         
           
           
               
               
           
         
         
           wherein X 1  represents chlorine, bromine or iodine, 
         
         with a compound of the formula (VI)
   R 1 -Q 1   (VI)
 
 wherein Q 1  represents —B(OH) 2 , a boronic ester, preferably pinacol boronate, or —BF 3   − K + , 
 
         under Suzuki coupling conditions to give a compound of the formula (I). 
       
     
     
         6 . The process according to  claim 5 , wherein, in the compound of formula (I) in the composition, R 3  represents ethyl and R 7  is 1,2,3-triazole substituted by chlorine or trifluoromethyl. 
     
     
         7 . The process according to  claim 5 , wherein the compound of formula (I) in the composition is 4-({(2S)-2-[4-{5-Chloro-2-[4-(trifluoromethyl)-1H-1,2,3-triazol-1-yl]phenyl}-5-methoxy-2-oxopyridin-1(2H)-yl]butanoyl}amino)-2-fluorobenzamide (enantiomer 2) of the formula 
       
         
           
           
               
               
           
         
       
     
     
         8 . The process according to  claim 5 , wherein the compound of formula (I) in the composition is 4-{[(2S)-2-{4-[5-Chloro-2-(4-chloro-1H-1,2,3-triazol-1-yl)phenyl]-5-methoxy-2-oxopyridin-1(2H)-yl}butanoyl]amino}-2-fluorobenzamide (enantiomer 2) of the formula