Synthesis of a highly potent leukocyte function‐associated antigen‐1 antagonist and its metabolite labeled with stable isotopes and carbon‐14, part 2 |
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Authors: | Bachir Latli Matt Hrapchak Yibo Xu Fenghe Qiu Dhileepkumar Krishnamurthy Chris H Senanayake |
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Institution: | Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., , Ridgefield, Connecticut, 06877 USA |
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Abstract: | (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. |
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Keywords: | leukocyte function‐associated antigen‐1 antagonist carbon‐14 carbon‐13 deuterium metabolites radiosynthesis |
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