1,1'-Carbonyldiimidazole → 3-chloro-2-hydroxy-N-(3-{4-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-phenyl)-benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-chloro-2-hydroxy-benzoic acid (0.11 g, 0.65 mmol) in acetonitrile (10 mL) is added carbodiimidazole (0.11 g, 0.71 mmol). After stirring the reaction mixture at 60° C. for 2 h, 1-[4-(3-amino-phenyl)-piperazin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone (0.20 g, 055 mmol) is added, followed by 1,8-diazabicycloundec-7-ene (0.1 mL, 0.82 mmol). After stirring overnight at 60° C., the reaction mixture is cooled down to RT and then solvent is evaporated and the resulting yellow oil is dissolved in ethylacetate (20 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL), 1N HCl (20 mL) and brine (20 mL). The organic layer is dried over sodium sulfate, filtered, and evaporated under reduced pressure. Cyclohexane is added dropwise to a solution of crude mixture in 1 mL ethylacetate to give after filtration 3-chloro-2-hydroxy-N-(3-{4-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-phenyl)-benzamide (Compound No. I.ao.003) (0.090 g, 26%). 1H-NMR (400 MHz, MeOD): δ=2.31 (s, 3H), 3.21-3.28 (m, 2H), 3.31-3.39 (m, 2H), 3.77-3.83 (m, 4H), 5.25 (s, 2H), 6.47 (s, 1H), 6.87-6.89 (m, 1H), 6.92-6.99 (m, 1H), 7.17-7.22 (m, 1H), 7.28-7.33 (m, 1H), 7.41-7.42 (m, 1H), 7.57-7.61 (m, 1H), 7.90-7.92 (m, 1H). MS: m/z=522 (M+1).

Provenance & Evidence