Synthesis of deuterium,tritium, and carbon‐14 labeled BIRB 796, a p38 MAP kinase inhibitor

1‐(5‐tert‐Butyl‐2‐p‐tolyl‐2H‐pyrazol‐3‐yl)‐3‐[4‐(2‐morpholin‐4‐yl‐ethoxy)naphthalen‐1‐yl]urea (BIRB 796), currently in clinical trials for the treatment of inflammatory diseases, is a potent inhibitor of p38 MAP kinase. Labeled BIRB 796 with stable and radioactive isotopes was required for metabolism, distribution, and absorption studies. We first report the synthesis of carbon‐14 labeled BIRB 796 with a specific activity of 2 GBq/mmol (54.2 mCi/mmol), using [¹⁴C]‐phosgene under modified Schotten–Baumann conditions; second the preparation of tritium‐labeled BIRB 796 with a specific activity of 659 GBq/mmol (17.81 Ci/mmol) by reductive dehalogenation of iodo‐BIRB 796 with tritium gas; and finally, the synthesis of ²H₈‐BIRB 796 using morpholine‐2,2,3,3,5,5,6,6‐²H₈ with isotopic enrichment of 98.9 at% ²H. Copyright © 2004 John Wiley & Sons, Ltd.