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@INPROCEEDINGS{Keuthen:911349,
      author       = {Keuthen, Yannick and Zlatopolskiy, Boris and Neumaier,
                      Bernd},
      title        = {{A}pplication of quaternary 1,4-diazabicyclo[2.2.2]octan
                      ({DABCO}) salts for {SN}2 “minimalist”
                      radiofluorination},
      issn         = {0969-8051},
      reportid     = {FZJ-2022-04641},
      year         = {2022},
      abstract     = {Objectives: The piperazine scaffold is a privileged
                      structuralmotif contained in numerous pharmaceuticals,
                      including severalPET-tracers. The aim of this work was to
                      evaluate quaternary DABCOsalts as precursors for the
                      preparation of probes containing a
                      N-(2-[18F]Fluoroethyl)piperazyl fragment by the
                      “minimalist” approach.[1]The latter allows for the
                      preparation of 18F-labeled compounds usingonly [18F]F– and
                      onium salt precursors, obviating the need for externalbase,
                      other additives and azeotropic drying.Methods: Quaternary
                      DABCO salts were prepared by direct
                      alkylation,(het)arylation, benzoylation or tosylation of
                      DABCO. If necessary,anion metathesis was carried out.
                      [18F]F– was eluted from ananion exchange resin with a
                      solution of the corresponding DABCO saltin MeOH. MeOH was
                      evaporated at 60°C for 8 min, the residue wastaken up into
                      a suitable solvent and heated in a Monowave 50 (AntonPaar,
                      Ostfildern-Scharnhausen, Germany) synthesis reactor. The
                      radiolabelingprocedure was optimized with respect to
                      reaction time,temperature, solvent and DABCO salt counter
                      ion. Radiolabeled compoundsprepared from alkyl-substituted
                      DABCO salts were isolatedby solid phase extraction (SPE).
                      Additionally,
                      N-(2-[18F]Fluoroethyl)-N’-pentynyl-piperazine ([18F]1)
                      isolated by SPE was clicked withbenzyl azide (2) to afford a
                      18F-fluorinated model triazole ([18F]3).Results: Reaction of
                      DABCO with alkyl halogenides or sulfonatesled to quaternary
                      alkyl DABCO salts, radiofluorination of which
                      under“minimalist” conditions furnished the corresponding
                      ring openingproducts, N-alkyl-N’-(2-[18F]Fluoroethyl)
                      piperazines, in $48–93\%RCYs$ (determined by HPLC) and,
                      after isolation by simple SPE, activityyields of up to
                      $31\%.$ Reaction of [18F]1 with 2 delivered [18F]3 in
                      aquantitative RCY (determined by HPLC). (Het)arylation,
                      benzoylationand tosylation of DABCO afforded the respective
                      N’-substituted piperazyl-N-ethyl DABCO salts (addition
                      products of two DABCO molecules)in up to $90\%$ yields as
                      single isolable products. 18F-Fluorinationof such substrates
                      mainly occurred via substitution of the DABCOgroup, leading
                      to formation of the corresponding
                      radiofluorinatedN-substituted
                      N’-(2-[18F]Fluoroethyl)piperazines in RCYs of
                      $28–46\%(determined$ by HPLC).Conclusions: Quaternary
                      DABCO salts are efficient precursors forrapid preparation of
                      probes containing an N-(2-[18F]Fluoroethyl)piperazinemotif
                      using the simple and convenient “minimalist”
                      protocol.Acknowledgement: This work was supported by the DFG
                      grantZL 65/4-1.Reference:[1] B. D. Zlatopolskiy, et al.;
                      Org. Biomol. Chem., 2014, 12, 8094.},
      month         = {May},
      date          = {2022-05-29},
      organization  = {24th International Symposium on
                       Radiopharmaceutical Sciences, Nantes
                       (France), 29 May 2022 - 3 Jun 2022},
      subtyp        = {After Call},
      cin          = {INM-5},
      ddc          = {570},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)6},
      doi          = {10.1016/S0969-8051(22)00134-2},
      url          = {https://juser.fz-juelich.de/record/911349},
}