Lin Ronghui, Gong Yong, Salter Rhys
Janssen Research & Development LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, Pennsylvania, USA.
J Labelled Comp Radiopharm. 2022 May 15;65(5):147-151. doi: 10.1002/jlcr.3967. Epub 2022 Mar 8.
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-D with 4-piperidone produced 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-D , which subsequently underwent catalytic hydrogenation to give 3-piperidin-4-yl-1H-indole-D . 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-D 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-D .
描述了多种氘标记的CCR2拮抗剂JNJ - 26131300，即[4-(1H-吲哚-3-基)-哌啶-1-基]-{1-[3-(3,4,5-三氟苯基)-丙烯酰基]-哌啶-4-基}-乙酸的合成。首先，吲哚-D与4-哌啶酮缩合生成3-(1,2,3,6-四氢吡啶-4-基)-1H-吲哚-D，随后进行催化氢化得到3-哌啶-4-基-1H-吲哚-D。接下来，由3-(3,4,5-三氟苯基)-丙烯酸和4-溴代哌啶-4-基-乙酸乙酯通过多步反应制备溴代-{1-[3-(3,4,5-三氟苯基)-丙烯酰基]-哌啶-4-基}-乙酸。3-哌啶-4-基-1H-吲哚-D与溴代-{1-[3-(3,4,5-三氟苯基)-丙烯酰基]-哌啶-4-基}-乙酸进行亲核偶联，得到所需化合物[4-(1H-吲哚-3-基)-哌啶-1-基]-{1-[3-(3,4,5-三氟苯基)-丙烯酰基]-哌啶-4-基}-乙酸-D。
