Triethylamine → HCID 90229526, compound

Participants

Reaction Steps

To a stirring solution of methyl 6-amino-2-chloro-1H-benzimidazole-4-carboxylate (400 mg, Example 135, Step 3) and triethylamine (209 μL) in THF (18 mL), 2-(trifluoromethyl)benzoyl chloride (316 μL) was dropped slowly under ice-cooling. After 1 hour, the reaction mixture was diluted with ethyl acetate, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain crude methyl 2-chloro-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxylate. This was dissolved in THF (15 mL) and MeOH (7 mL), 1N aqueous lithium hydroxide solution (9 mL) was added, and it was stirred at room temperature overnight. THF and MeOH were removed under reduced pressure. To the residue was added water, and it was neutralized with 1N hydrochloric acid under ice-cooling. The precipitation was collected by filtration to obtain crude 2-chloro-6-({[2-(trifluoromethyl)phenyl]carbonyl}amino)-1H-benzimidazole-4-carboxylic acid. This was dissolved in THF (10 mL), 40% aqueous dimethylamine solution (7 mL) was added, and it was stirred at 120° C. for 14 hours. The reaction mixture was cooled to room temperature, and THF was removed under reduced pressure. To the residue was added water, and the pH was adjusted to 3-4 with 1N hydrochloric acid under ice-cooling. The precipitate was collected by filtration, washed with diethyl ether, and dried under reduced pressure to obtain the titled compound (589 mg) as slightly yellow solid.

Provenance & Evidence