Hydrochloric Acid → HCID 178524916, compound

Participants

Reaction Steps

A solution of methyl 4-chloro-1H-imidazole-5-carboxylate (0.061 g, 0.4 mmol) was stirred in a solution of MeOH (2 mL), dioxane (2 mL) and 2N NaOH (1.9 mL, 3.8 mmol) at RT for 4 days. The reaction mixture was then acidified by addition of 1M HCl (20 mL) and extracted with EtOAc. The organic extracts were dried (Na2SO4), and the solvent was evaporated to provide 4-chloro-1H-imidazole-5-carboxylic acid (0.0523 g, 94%) as a white solid which was used without further purification. 4-Chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide was prepared in a similar manner as described herein from 3-{[3-aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.054 g, 0.17 mmol), 4-chloro-1H-imidazole-5-carboxylic acid (0.026 g, 0.17 mmol), HATU (0.086 g, 0.23 mmol), DIPEA (0.039 mL, 0.23 mmol) and DMF (2 mL). Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.008 g, 10%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 13.16 (br. s., 1H), 8.24 (br. s., 1H), 7.82 (s, 1H), 7.78 (s, 1H), 7.45-7.54 (m, 3H), 7.35-7.42 (m, 1H), 4.54 (s, 2H). ES-LCMS: m/z 439.0, 441.0 (M+1).

Provenance & Evidence