Process for Manufacturing a Naphthyridine Derivative

Abstract

The invention relates to a process and synthetic intermediates that can be used for manufacturing the compound of formula (1-6) which is a synthetic intermediate useful in the preparation of antibiotic compounds.

1 . The compound of formula I-3 
       
         
           
           
               
               
           
         
         or a salt of that compound. 
       
     
     
         2 . A process for manufacturing the compound of formula I-3 as defined in  claim 1 , said process comprising the reaction of the compound of formula I-2 
       
         
           
           
               
               
           
         
         with a nitration reagent or mixture of reagents at a temperature from 20° C. to 100° C. 
       
     
     
         3 . The process of  claim 2 , wherein the compound of formula I-2 is obtained by
 a) reacting of the compound of formula I-1 below   
       
         
           
           
               
               
           
         
         with 2,2-dimethyl-1,3-dioxanc-4,6-dione and triethylorthoformate in an alkanol, in a mixture of at least two alkanols or in a mixture of solvents comprising at least one polar aprotic solvent and at least one alkanol; and 
         b) heating the intermediate obtained after step a) in a solvent or mixture of solvents. 
       
     
     
         4 . Use of the compound of formula I-3 as defined in  claim 1 , or a salt thereof, in a process for manufacturing the compound of formula I-5 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         5 . Use of the compound of formula I-3 as defined in  claim 1 , or a salt thereof, in a process for manufacturing the compound of formula I-6 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         6 . A compound of formula I-4 
       
         
           
           
               
               
           
         
         wherein X is Br or Cl; 
         or a salt thereof. 
       
     
     
         7 . A compound of formula I-4 according to  claim 6 , wherein X is Br;
 or a salt thereof.   
     
     
         8 . A compound of formula I-4 according to  claim 6 , wherein X is Cl;
 or a salt thereof.   
     
     
         9 . A process for manufacturing the compound of formula I-4 as defined in  claim 6 , or a salt thereof, said process comprising the reaction of the compound of formula I-3 as defined in  claim 1  with pentachlorophosphorane, tribromophosphine, trichlorophosphine, phosphoryl tribromide or phosphoryl trichloride. 
     
     
         10 . Use of the compound of formula I-4 as defined in  claim 6 , or a salt thereof, in a process for manufacturing the compound of formula I-6 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         11 . A process for manufacturing the compound of formula I-5 
       
         
           
           
               
               
           
         
         said process comprising the reaction of the compound of formula I-4 as defined in one of  claims 6  to  8  with hydrogen in an alkanol in the presence of a base and of a catalyst selected from Raney nickel, iron, palladium and platinum. 
       
     
     
         12 . The process of  claim 11 , wherein the base is triethylamine. 
     
     
         13 . The process of  claim 11  or  12 , wherein the alkanol is methanol. 
     
     
         14 . A process for manufacturing the compound of formula I-6 
       
         
           
           
               
               
           
         
         said process comprising the following steps: 
         a) reacting the compound of formula I-5 
       
       
         
           
           
               
               
           
         
         with a couple of reagents consisting of a fluorination reagent and a nitrite reagent, and 
         b) heating the diazonium salt obtained after step a). 
       
     
     
         15 . The process of  claim 14 , which comprises reacting the compound of formula I-5 with pyridine and NaNO 2  or KNO 2  in liquid HF followed by heating the reaction mixture.