Synthesis of 13C-labeled verapamil compounds

Two 13C‐labeled verapamil compounds were prepared. 2‐(3,4‐Dimethoxyphenyl)‐2‐isopropyl‐5‐[2–(3,4‐dimethoxyphenyl‐1–[13C]‐ethyl)methylamino]‐valeronitrile was synthesized from 2–(3,4‐dimethoxyphenyl)‐1–[13C]‐ethylamine, which was prepared from 3,4‐dimethoxybenzyl chloride by displacement with 13C‐labeled KCN followed by diborane reduction. 2‐(3,4‐Di‐[13C]‐methoxyphenyl)‐2‐isopropyl‐5–[2–(3,4‐di–[13C]‐methoxyphenethyl)methylamino]‐valeronitrile containing 50% incorporation of 13C in the N‐methyl group was prepared via demethylation of verapamil and subsequent re‐methylation with 13C‐labeled CH3I.