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The radiosynthesis of nca [ O‐methyl ‐ 11 C]viqualine, through an N ‐trityl‐protected intermediate, as a potential pet radioligand for 5HT re‐uptake sites
Author(s) -
Pascali Claudio,
Pike Victor W.,
Turton David R.
Publication year - 1990
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580281114
Subject(s) - radiosynthesis , chemistry , yield (engineering) , desmethyl , hydrolysis , bicyclic molecule , alkylation , tetrabutylammonium hydroxide , nitrogen , radioligand , nuclear chemistry , medicinal chemistry , organic chemistry , binding site , biochemistry , materials science , microbiology and biotechnology , in vivo , metabolite , metallurgy , biology , catalysis
Viqualine, {4‐[3‐[3( R )‐ethenyl‐4( R )‐piperidinyl]propyl]‐6‐methoxyquinoline}, has been labelled in the O ‐methyl position with no‐carrier‐added (nca) carbon‐11 ( t 1/2 = 20.4 min; β + = 99.8%) to provide a potential radioligand for PET studies of 5HT re‐uptake sites. Direct treatment of desmethyl ‐viqualine with nca [ 11 C]iodomethane gave [ O‐methyl ‐ 11 C]viqualine as only a minor product. NMR data suggested that the dominant product is that from the [ 11 C]alkylation of the competing piperidino‐nitrogen. Protection of this nitrogen with the trityl group, followed by treatment with nca [ 11 C]iodomethane in dimethyl sulphoxide with sodium hydroxide as base, and then rapid deprotection by mild acid hydrolysis gave nca [ O‐methyl ‐ 11 C]viqualine as the main crude product (27% radiochemical yield, decay‐corrected from [ 11 C]iodomethane). Radiochemically and chemically pure nca [ O‐methyl ‐ 11 C]viqualine was obtained by work up on C18 Sep‐pak followed by reverse phase HPLC. The radiosynthesis, including final formulation for i.v. administration, takes 56 min after producing the carbon‐11 as [ 11 C]carbon dioxide by the 14 N(p,α) 11 C reaction. This radiosynthesis illustrates the potential utility of the trityl group for the protection of nitrogen in rapid carbon‐11 radiochemistry.