Synthesis of [19, 35, 36-13C3]-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 13C at positions C19, 35, and 36 was produced. A commercially available [13C]-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 [13C]-labeled tolyl boronic ester by the Suzuki–Miyaura reaction and a [13C]-labeled aniline segment by amide bond formation.

[13C3]-labeled TAK779 (2) was produced by introducing 100% 13C-enriched isotope carbon C-19, -35, and -36. For convenience, the readily available [13C]-methyl iodide was employed for labeling.Figure optionsDownload as PowerPoint slide