Convergent synthesis of two 14 C‐labeled β 3 ‐adrenergic receptor agonists

The synthesis of β 3 ‐adrenergic receptor agonists A and B with radiolabeled amide fragment, required for drug disposition studies, was accomplished based on initial formation of 2‐(4‐(2‐amino‐2‐methylpropyl)phenoxy)‐5‐[ 14 C]‐cyanopyridine by the reaction of 2‐bromo‐5‐iodopyridine with para ‐substituted phenol, and following cyanation of aromatic iodide with potassium cyanide‐[ 14 C]. After the coupling of the resulted amine with glycidyl derivatives of 4‐hydroxyindole and 4‐hydroxycarbazole, the corresponding nitriles were hydrolyzed with basic hydrogen peroxide to obtain target amides A and B . Copyright © 2006 John Wiley & Sons, Ltd.