Process for preparing ceftaroline fosamil

Abstract

The present invention relates to a novel process for preparing ceftaroline fosamil as well as to intermediates of this process.

The invention claimed is: 
     
       1. A compound having the formula (1) 
       
         
           
           
               
               
           
         
       
       wherein
 Phos is a phosphate group; and 
 X is a cation selected from the group consisting of a magnesium cation and an imidazolium cation which can be optionally substituted by one or more C 1-6  alkyl groups; as well as a pharmaceutically acceptable solvate thereof selected from an acetic acid solvate or an acetonitrile solvate. 
 
     
     
       2. The compound according to  claim 1 , wherein X is an imidazolium cation which can be optionally substituted by one or more C 1-6  alkyl groups. 
     
     
       3. The compound according to  claim 2 , wherein X is an imidazolium cation or a methyl-imidazolium cation. 
     
     
       4. The compound according to  claim 1 , wherein X is a magnesium cation. 
     
     
       5. A process comprising the steps of:
 (i) reacting a compound having the formula (2) or a salt thereof 
 
       
         
           
           
               
               
           
         
          with a compound having the formula (3) 
       
       
         
           
           
               
               
           
         
          wherein Hal is a halogen; and 
         (ii) adding a reagent selected from the group consisting of a magnesium salt and an imidazole which can be optionally substituted by one or more C 1-6  alkyl groups; to provide a compound having the formula (1) 
       
       
         
           
           
               
               
           
         
         wherein
 Phos is a phosphate group; and 
 X is a cation selected from the group consisting of a magnesium cation and an imidazolium cation which can be optionally substituted by one or more C 1-6  alkyl groups. 
 
       
     
     
       6. A process comprising the steps of:
 (a) reacting a compound having the formula (2) or a salt thereof 
 
       
         
           
           
               
               
           
         
          with a silane to provide a compound having the formula (5) 
       
       
         
           
           
               
               
           
         
          wherein R is independently selected from a C 1-6  alkyl group; 
         (b) reacting the compound having the formula (5) with a compound having the formula (3) 
       
       
         
           
           
               
               
           
         
          wherein Hal is a halogen; 
         (c) removing the silyl group —SiR 3  from the resultant compound; and 
         (d) adding a reagent selected from the group consisting of a magnesium salt and an imidazole which can be optionally substituted by one or more C 1-6  alkyl groups; 
          to provide a compound having the formula (1) 
       
       
         
           
           
               
               
           
         
         wherein
 Phos is a phosphate group; and 
 X is a cation selected from the group consisting of a magnesium cation and an imidazolium cation which can be optionally substituted by one or more C 1-6  alkyl groups. 
 
       
     
     
       7. The process according to  claim 5 , wherein the magnesium salt is selected from the group consisting of magnesium acetate as well as hydrates thereof. 
     
     
       8. The process according to  claim 5 , wherein the compound having the formula (1) is transformed into a compound having the formula (4) 
       
         
           
           
               
               
           
         
         wherein Y is CH 3 COOH, CH 3 CH 2 COOH or CH 3 CN; and 
         n is 0 to 5. 
       
     
     
       9. The process according to  claim 6 , wherein the magnesium salt is selected from the group consisting of magnesium acetate as well as hydrates thereof. 
     
     
       10. The process according to  claim 6 , wherein the compound having the formula (1) is transformed into a compound having the formula (4) 
       
         
           
           
               
               
           
         
         wherein Y is CH 3 COOH, CH 3 CH 2 COOH or CH 3 CN; and 
         n is 0 to 5. 
       
     
     
       11. The compound according to  claim 1 , wherein the compound is an acetic acid solvate or acetonitrile solvate. 
     
     
       12. A process comprising the step of transforming a compound having the formula (1) 
       
         
           
           
               
               
           
         
         wherein 
         Phos is a phosphate group; and 
         X is a cation selected from the group consisting of a magnesium cation and an imidazolium cation which can be optionally substituted by one or more C 1-6  alkyl groups; 
         into a compound having the formula (4) 
       
       
         
           
           
               
               
           
         
         wherein Y is CH 3 COOH, CH 3 CH 2 COOH or CH 3 CN; and 
         n is 0 to 5.