title: Rapid Room-Temperature11C-Methylation of Arylamines with [11C]Methyl Iodide Promoted by Solid Inorganic Bases in DMF.
abstract: 11[C]Methyl iodide is the most widely used reagent for labeling radiotracers with carbon-11 (t1/2= 20.4 min) for molecular imaging with positron emission tomography. However, some substrates for labeling, especially primary arylamines and pyrroles, are sluggishly reactive towards [11C]methyl iodide. We found that insoluble inorganic bases, especially Li3N or Li2O, are effective in promoting rapid reactions (≤ 10 min) of such substrates with no-carrier-added [11C]methyl iodide in DMF at room temperature to give11C-methylated products in useful radiochemical yields. In particular, we discovered that some primary arylamines in Li3N-DMF were converted into their formanilides, and that these were readilyN-methylated with [11C]methyl iodide, preceding easy basic hydrolysis to the desired [11C]N-methyl secondary arylamines. Use of a solid base permitted selective reaction at an arylamino group and in some cases also avoided undesirable side reaction, such as ester group hydrolysis. An ultrasound device proved useful to provide remote and constant agitation of the radioactive heterogeneous reaction mixtures, but imparted no 'ultrasound-specific' chemical effect.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Room B3 C346A, Bethesda MD 20892, USA.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Cai
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Room B3 C346A, Bethesda MD 20892, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Room B3 C346A, Bethesda MD 20892, USA.
authors.forename: Xuelei
authors.initials: X
authors.lastname: Guo
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Room B3 C346A, Bethesda MD 20892, USA.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Pike
keywords: arylamine; carbon-11; inorganic base; methylation; ultrasound