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

The synthesis of 1-(5-chloro-2-{2-[(2R)-4-(4-[¹⁸F]fluorobenzyl)-2methylpiperazin-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]fluorobenaldehyde with a piperazine derivative 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