1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-[4-(benzyloxy)phenyl]-N-[2-(2-piperidin-1-ylethyl)-2H-indazol-4-yl]acetamide

Participants

Reaction Steps

4-Nitro-2-(2-piperidin-1-yl-ethyl)-2H-indazole (0.160 g, 0.583 mmol), iron powder (0.326 g, 5.84 mmol) and ammonium chloride (0.0185 g, 0.346 mmol) was suspended in a 4:1 ethanol/H2O solution and heated to reflux for 3 hours. The mixture was cooled to room temperature, the solvents removed in vacuo and the residue stirred in triethylamine/ethyl acetate (1/4, 5 mL). The mixture was filtered through a plug of silica gel and rinsed with triethylamine/ethyl acetate (1/4) and the filtrate was concentrated to provide a pale white solid. The solid (40.0 mg, 0.164 mmol) was dissolved in 3 mL of N,N-dimethylformamide and (4-benzyloxy-phenyl)-acetic acid (0.0470 g, 0.194 mmol), PS-EDCI (1.30 mmol/g, 0.378 g, 3 equiv), N-Hydroxybenzotriazole (0.0330 g, 0.244 mmol) and diisopropylethylamine (0.0850 mL, 0.488 mmol) were added and the reaction vessel was placed on a shaker table for 6 hours. The mixture was concentrated under vacuo and the residue dissolved in 1.5 mL of a 1:1 mixture of dimethylsulfoxide/methanol and purified by preparative reverse-phase HPLC. 1H NMR (300 MHz, DMSO-D6) δ ppm 1.37 (m, 2 H) 1.46 (m, 4 H) 2.39 (m, 4 H) 2.79 (t, J=6.61 Hz, 2 H) 3.68 (s, 2 H) 4.51 (t, J=6.61 Hz, 2 H) 5.08 (s, 2 H) 6.92 (m, 2 H) 7.14 (m, 1 H) 7.39 (m, 9 H) 8.47 (m, 1 H) 10.02 (s, 1 H); MS (DCI/NH3) m/z 469 [M+H]+.

Provenance & Evidence