Synthesis of [19, 35, 36-(13)C(3)]-labeled TAK779 as a molecular probe.

N,N-Dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium chloride (TAK779) is a potent and selective non-peptide CCR5 antagonist. To use a site-specifically labeled form as a molecular probe, TAK779 containing (13)C at positions C19, 35, and 36 was produced. A commercially available [(13)C]-methyl iodide was employed for the labeling. Starting from a known carboxylic acid segment containing no labeled carbon, the labeled TAK779 was constructed by the successive coupling of [(13)C]-labeled tolyl boronic ester by the Suzuki-Miyaura reaction and a [(13)C]-labeled aniline segment by amide bond formation.