Synthesis of deuterium‐labeled CCR2 antagonist JNJ‐26131300, [4‐(1H‐indol‐ 3‐yl)‐piperidin‐1‐yl]‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid. (8th March 2022)

• Record Type: Journal Article
• Authors: Lin, Ronghui; Gong, Yong; Salter, Rhys
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 65:Number 5(2022)
• Page Start: 147
• Page End: 151
• Publication Date: 2022-03-08
• Subjects: 3‐piperidin‐4‐yl‐1H‐indole -- CCR2 antagonist -- isotope label -- substituted dipiperidine analog -- synthesis; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3967
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : Synthesis of multiple deuterium‐labeled CCR2 antagonist JNJ‐26131300, that is, [4‐(1 H ‐indol‐3‐yl)‐piperidin‐1‐yl]‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid, is described. First, condensation of indole‐D7 with 4‐piperidone produced 3‐(1, 2, 3, 6‐tetrahydropyridin‐4‐yl)‐1 H ‐indole‐D5, which subsequently underwent catalytic hydrogenation to give 3‐piperidin‐4‐yl‐1 H ‐indole‐D5 . Next, bromo‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid was prepared through multiple steps from 3‐(3, 4, 5‐trifluoro‐phenyl)‐acrylic acid and bromo‐piperidin‐4‐yl‐acetic acid ethyl ester. Nucleophilic coupling of 3‐piperidin‐4‐yl‐1 H ‐indole‐D5 with bromo‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid afforded the desired compound [4‐(1 H ‐indol‐3‐yl)‐piperidin‐1‐yl]‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid‐D5 . Abstract : Synthesis of multiple deuterium‐labeled CCR2 antagonist JNJ‐26131300, [4‐(1 H ‐indol‐3‐yl)‐piperidin‐1‐yl]‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid, is described. First, condensation of indole‐D7 with 4‐piperidone produced 3‐(1, 2, 3, 6‐tetrahydropyridin‐4‐yl)‐1 H ‐indole‐D5, which subsequently underwent catalytic hydrogenation to give 3‐piperidin‐4‐yl‐1 H ‐indole‐D5 . Next, bromo‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid was prepared through multiple steps from 3‐(3, 4, 5‐trifluoro‐phenyl)‐acrylic acid and bromo‐piperidin‐4‐yl‐acetic acid ethyl ester. Nucleophilic coupling of 3‐piperidin‐4‐yl‐1 H ‐indole‐D5 with bromo‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid afforded the desired compound [4‐(1 H ‐indol‐3‐yl)‐piperidin‐1‐yl]‐{1‐[3‐(3, 4, 5‐trifluoro‐phenyl)‐acryloyl]‐piperidin‐4‐yl}‐acetic acid‐D5 .