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, i.e. [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.

Source: Journal of Labelled Compounds and Radiopharmaceuticals - February 26, 2022 Category: Biochemistry Authors: Ronghui Lin, Yong Gong, Rhys Salter Tags: PRACTITIONER PROTOCOL ‐ SYNTHESIS Source Type: research