Trifluoromethanesulfonic acid → 1-{4-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-5,5-dimethylimidazolidin-2-one

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Reaction Steps

To a mixture of (4-bromo-2-fluorophenyl) [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (157 mg) described in Preparation Example 114, 1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one (112 mg) described in Preparation Example 54, cesium carbonate (261 mg) and copper(I) iodide (38 mg) were added 1,4-dioxane (10 mL) and N,N′-dimethylethylenediamine (43 μL), and the mixture was stirred with heating under reflux for 32 hr. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give 3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one. The obtained 3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one was dissolved in dichloromethane (5 mL), trifluoromethanesulfonic acid (75 μL) was added, and the mixture was stirred at room temperature for 4 hr. To the reaction mixture was added 5% aqueous sodium hydrogen carbonate solution, and the solvent was evaporated, and the mixture was extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium hydrogen carbonate solution, and saturated brine, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was purified by silica gel column chromatography (ethyl acetate:methanol) to give the title compound (30 mg).

Provenance & Evidence