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

✍ Scribed by Bachir Latli; Matt Hrapchak; Yibo Xu; Fenghe Qiu; Dhileepkumar Krishnamurthy; Chris H. Senanayake

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 600 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1934

✦ Synopsis

2-[(R)-7-(3,5-Dichlorophenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxybenzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3sulfonylamino]-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 [ 13 C 2 , 2 H 3 ]-(1) using [3,3,3-2 H]-D-alanine and [ 13 C 2 ]-glycine in 15 steps and 2.5% overall yield. With the availability of [ 13 C 6 ]-3,5-dichloroaniline, the sulfonamide [ 13 C 6 ]-( 2) was prepared in 12 steps and in 5.6% overall yield. For the carbon-14 synthesis, a six-step synthesis gave both compounds [ 14 C]-(1) and [ 14 C]-(2) from the common sulfonyl chloride intermediate [ 14 C]-(15) in 18% and 4% radiochemical yields and specific activities of 44 and 40.5 mCi/mmol, respectively.