1-Hydroxybenzotriazole → [2,4-Bis(1,1-dioxo-1lambda6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone

Participants

Reaction Steps

2,4-Bis(1,1-dioxo-1λ6-isothiazolidin-2-yl)benzoic acid (200 mg) described in Preparation Example 34, 1-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine (121 mg) described in Preparation Example 86, and 1-hydroxybenzotriazole 1 hydrate (79 mg) were dissolved in N,N-dimethylformamide (3 mL), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (112 mg) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (ethyl acetate:hexane) to give [2,4-bis(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone. The obtained [2,4-bis(1,1-dioxo-1λ6-isothiazolidin-2-yl)phenyl][4-(3-cyclopropyl-5-methylpyridin-2-yl)piperazin-1-yl]methanone (240 mg) was dissolved in ethyl acetate, 4N hydrogen chloride/ethyl acetate (0.11 mL) was added, and the precipitate was collected by filtration to give the title compound (104 mg).

Provenance & Evidence