Diisopropylethylamine → HCID 67202699, compound

Participants

Reaction Steps

4-(Trifluoromethyl)nicotinic acid (88; 1.00 g, 5.23 mmol) was taken up in DMF (8 mL) along with methyl 2,3-diaminobenzoate (118; 0.86 g, 5.23 mmol), HATU (2.98 g, 7.84 mmol) and DIEA (1.82 mL, 10.5 mmol). The reaction mixture was stirred at room temperature for 18 h. It was then diluted with EtOAc, washed with water, dried (Na2SO4) and concentrated under reduced pressure to afford crude methyl 2-amino-3-(4-(trifluoromethyl)nicotinamido)benzoate. This material was taken up in 5 mL of glacial acetic acid and stirred at 60° C. for 18 h. The reaction mixture was stirred at 90° C. for an additional 8 h. It was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with EtOAc, washed with dilute aqueous NaHCO3, dried (Na2SO4) and concentrated under reduced pressure to afford crude methyl 2-(4-(trifluoromethyl)pyridin-3-yl)-1H-benzo[d]imidazole-4-carboxylate. This material was taken up in MeOH (8 mL) and H2O (8 mL) containing LiOH (0.4 g) and stirred at room temperature for 18 h. The reaction mixture was concentrated under reduced pressure and neutralized with 6 N HCl. The resulting solids were collected by filtration and dried to afford 570 mg of 2-(4-(trifluoromethyl)pyridin-3-yl)-1H-benzo[d]imidazole-4-carboxylic acid (35% yield from methyl 2,3-diaminobenzoate) 119. MS (ESI) calcd for C14H8F3N3O2: 307.06; found: 308 [M+H].

Provenance & Evidence