Solid-phase fluorination of benzothiazoles

Abstract

The invention provides a process for the production of an 18 F-labelled tracer which comprises treatment of a solid support-bound precursor of formula (I) SOLID SUPPORT-LINKER-X-TRACER  (I) wherein X is a group which promotes nucleophilic substitution at a specific site on the attached TRACER and the TRACER is of formula (A)

What is claimed is: 
     
         1 - 8 . (canceled) 
     
     
         9 . A compound of formula (I), (Ia), (Ib), or (III):
   (i) SOLID SUPPORT-LINKER-X-TRACER  (I)
   wherein X is a group which promotes nucleophilic substitution at a specific site on the attached TRACER and the TRACER is of formula (A)   
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are independently selected from hydrogen, a protecting group, C 1-6  alkyl, C 1-6  hydroxyalkyl, and C 1-6  haloalkyl; 
         R 3  to R 10  are independently selected from hydrogen, halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, hydroxy, cyano, and nitro; 
         and one of the groups R 1  to R 10  is bonded to the SOLID SUPPORT-LINKER-X—;
   (ii) SOLID SUPPORT-LINKER-SO 2 —O-TRACER  (Ia)
 
 
         wherein the TRACER is of formula (Aa) 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are independently selected from hydrogen, a protecting group, C 1-6  alkyl, C 1-6  hydroxyalkyl, and C 1-6  haloalkyl; 
         R 3  to R 10  are independently selected from hydrogen, halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, hydroxy, cyano, and nitro; 
         in which either (a) an R 1 C 1-6  alkyl group or (b) an R 3  to R 10 C 1-6  alkyl or C 1-6  alkoxy group is bonded to the SOLID SUPPORT-LINKER-SO 2 —O— in formula (Ia); 
       
       
         
           
           
               
               
           
         
         wherein Y −  is an anion and the TRACER is of formula (Ab) 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are independently selected from hydrogen, a protecting group, C 1-6  alkyl, C 1-6  hydroxyalkyl, and C 1-6  haloalkyl; 
         one of R 3  to R 10  is a bond to the SOLID SUPPORT-LINKER-I + — group in formula (Ib) and the others are independently selected from hydrogen, halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, hydroxy, cyano, and nitro; or 
       
       
         
           
           
               
               
           
         
         wherein R 11  and R 12  are independently selected from C 1-6  alkyl and the TRACER is a compound of formula (Ac): 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 1  and R 2  are independently selected from hydrogen, a protecting group, C 1-6  alkyl, C 1-6  hydroxyalkyl, and C 1-6  haloalkyl; 
         one of R 3  to R 10  is a bond to the Sn in formula (III) and the others are independently selected from hydrogen, halo, C 1-6  alkyl, C 1-6  haloalkyl, C 1-6  hydroxyalkyl, C 1-6  alkoxy, C 1-6  haloalkoxy, hydroxy, cyano, and nitro. 
       
     
     
         10 . A radiopharmaceutical kit for the preparation of an  18 F-labelled tracer for use in PET, which comprises:
 (i) a vessel containing a compound of formula (I), (Ia), or (Ib) as defined in  claim 9 ; and   (ii) means for eluting the vessel with a source of  18 F − ;   (iii) an ion-exchange cartridge for removal of excess  18 F − .   
     
     
         11 . A cartridge for a radiopharmaceutical kit for the preparation of an  18 F-labelled tracer for use in PET which comprises:
 (i) a vessel containing a compound of formula (I), (Ia), or (Ib) as defined in  claim 9 ; and   (ii) means for eluting the vessel with a source of  18 F − .   
     
     
         12 . A radiopharmaceutical kit for the preparation of an  18 F-labelled tracer for use in PET, which comprises:
 (i) a vessel containing a compound of formula (III) as defined in  claim 9 ; and   (ii) means for eluting the vessel with a source of  18 F − .   
     
     
         13 . A cartridge for a radiopharmaceutical kit for the preparation of an  18 F-labelled tracer according to  claim 12  for use in PET which comprises:
 (i) a vessel containing a compound of formula (III) as defined in  claim 9 ; and 
 (ii) means for eluting the vessel with a source of  18 F. 
 
     
     
         14 . A method for obtaining a diagnostic PET image which comprises the step of using a radiopharmaceutical kit according to  claim 10  or a cartridge for a radiopharmaceutical kit according to  claim 11 .