Method for production of f-18 labeled amyloid beta ligands

Abstract

This invention relates to methods, which provide access to [F-18]fluoropegylated (aryl/heteroaryl vinyl)-phenyl methyl amine derivatives.

1 . A Method for producing a compound of Formula I 
       
         
           
           
               
               
           
         
         comprising the steps of: 
         Step 1: Radiolabeling compound of Formula II with a F-18 fluorinating agent, to obtain compound of Formula I, if R═H or to obtain compound of Formula III, if R═PG 
       
       
         
           
           
               
               
           
         
         Step 2: If R═PG, cleavage of the protecting group PG to obtain a compound of Formula I 
         Step 3: Purification and Formulation of a compound of Formula I 
         wherein: 
         n=1-6, 
         X is selected from the group consisting of 
         a) CH, 
         b) N, 
         R is selected from the group consisting of 
         a) H, 
         b) PG, 
         PG is an “Amine-protecting group”, 
         LG is a leaving group, 
         wherein in step 3 a HPLC method is used, wherein the HPLC solvent or solvent mixture is part of an injectable Formulation of compound I suitable for injection into humans. 
       
     
     
         2 . A method according to  claim 1 , wherein PG is selected from the group consisting of:
 a) Boc,   b) Trityl and   c) 4-Methoxytrityl.   
     
     
         3 . A method according to  claim 1 , wherein LG is selected from the group consisting of:
 a) Halogen and   b) Sulfonyloxy,   Halogen is chloro, bromo or iodo.   
     
     
         4 . A method according to  claim 3 , wherein Sulfonyloxy is selected from the group comprising:
 a) Methanesulfonyloxy,   b) p-Toluenesulfonyloxy,   c) (4-Nitrophenyl)sulfonyloxy,   d) (4-Bromophenyl)sulfonyloxy.   
     
     
         5 . A method according to  claim 1 , wherein n=3 and X═CH. 
     
     
         6 . A method according to  claim 1 , wherein n=3, X═CH, R=Boc, and LG=Methanesulfonyloxy. 
     
     
         7 . A method according to  claim 1 , wherein the HPLC solvent is selected from the group consisting of ethanol, an aqueous buffer or an ethanol/aqueous buffer mixture. 
     
     
         8 . A method according to  claim 7 , wherein the aqueous buffer is selected from the group of solutions of sodium chloride, sodium phosphate buffer, ascorbic acid, ascorbate buffer, or mixtures thereof. 
     
     
         9 . A method according to  claim 1 , wherein 10-50 μmol of a compound of Formula II is used. 
     
     
         10 . A method according to  claim 1 , wherein the method is performed as a fully automated process. 
     
     
         11 . A kit, comprising a sealed vial containing a compound of Formula II and a sealed vial containing a solution for HPLC that can be part of an injectable Formulation of compound I suitable for injection into humans. 
     
     
         12 . A kit according to  claim 10 , wherein the solution for HPLC that can be part of an injectable Formulation of compound I suitable for injection into humans is selected from the group consisting of ethanol, an aqueous buffer or an ethanol/aqueous buffer mixture. 
     
     
         13 . A kit according to  claim 12 , wherein the aqueous buffer is selected from the group consisting of sodium chloride, sodium phosphate buffer, ascorbic acid, ascorbate buffer, or mixtures thereof.