Synthesis of a highly potent leukocyte function‐associated antigen‐1 antagonist and its metabolite labeled with stable isotopes and carbon‐14, part 2

(S)‐2‐(R)‐7‐(3,5‐Dichlorophenyl)‐5‐methyl‐6‐oxo‐5‐(4‐trifluoromethoxybenzyl)‐6,7‐dihydro‐5H‐imidazo1,2‐a]imidazole‐3‐sulfonylamino]‐proprionamide (1), a potent lymphocyte function‐associated antigen‐1 antagonist and its sulfonamide metabolite (2) labeled with stable isotopes and carbon‐14 were prepared for Drug Metabolism and PharmacoKinetics and other studies. A long linear route was used to prepare ¹³C₂, ²H₃]‐(1) using 3,3,3‐²H]‐D‐alanine and ¹³C₂]‐glycine in 15 steps and 2.5% overall yield. With the availability of ¹³C₆]‐3,5‐dichloroaniline, the sulfonamide ¹³C₆]‐(2) was prepared in 12 steps and in 5.6% overall yield. For the carbon‐14 synthesis, a six‐step synthesis gave both compounds ¹⁴C]‐(1) and ¹⁴C]‐(2) from the common sulfonyl chloride intermediate ¹⁴C]‐(15) in 18% and 4% radiochemical yields and specific activities of 44 and 40.5 mCi/mmol, respectively. Copyright © 2011 John Wiley & Sons, Ltd.