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

Synthesis of multiple 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, is described. First, condensation of indole-D7 with 4-piperidone produced 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-D5, which subsequently underwent catalytic hydrogenation to give 3-piperidin-4-yl-1H-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-1H-indole-D5 with bromo-{1-[3-(3,4,5-trifluoro-phenyl)-acryloyl]-piperidin-4-yl}-acetic acid afforded the desired compound [4-(1H-indol-3-yl)-piperidin-1-yl]-{1-[3-(3,4,5-trifluoro-phenyl)-acryloyl]-piperidin-4-yl}-acetic acid-D5. Synthesis of multiple deuterium-labeled CCR2 antagonist JNJ-26131300, that is, [4-(1H-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)-1H-indole-D5, which subsequently underwent catalytic hydrogenation to give 3-piperidin-4-yl-1H-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 c...

Source: Journal of Labelled Compounds and Radiopharmaceuticals - March 9, 2022 Category: Biochemistry Authors: Ronghui Lin, Yong Gong, Rhys Salter Tags: PRACTITIONER PROTOCOL ‐ SYNTHESIS Source Type: research