18F‐labelling of a potent nonpeptide CCR1 antagonist: synthesis of 1‐(5‐chloro‐2‐{2‐[(2R)‐4‐(4‐[18F]fluorobenzyl)‐2‐methylpiperazin‐1‐yl]‐2‐oxoethoxy}phenyl)urea in an automated module

The synthesis of 1‐(5‐chloro‐2‐{2‐(2R)‐4‐(4‐¹⁸F]fluorobenzyl)‐2‐methylpiperazin‐1‐yl]‐2‐oxoethoxy}phenyl)urea ( ¹⁸F]4 ), a potent nonpeptide CCR1 antagonist, is described as a module‐assisted two‐step one‐pot procedure. The final product was obtained utilizing the reductive amination of the formed 4‐¹⁸F]fluorobenzaldehyde ( 2 ) with a piperazine derivative 3 and sodium cyanoborohydride. After HPLC purification of the final product ¹⁸F]4 , its solid phase extraction, formulation and sterile filtration, the isolated (not decay‐corrected) radiochemical yields of ¹⁸F]4 were between 7 and 13% (n=28). The time of the entire manufacturing process did not exceed 95 min. The radiochemical purity of ¹⁸F]4 was higher than 95%, the chemical purity ?60% and the enantiomeric purity >99.5%. The specific radioactivity was in the range of 59–226 GBq/µmol at starting radioactivities of 23.6–65.0 GBq ¹⁸F]fluoride. Copyright © 2006 John Wiley & Sons, Ltd.