N,N'-Dimethylethylenediamine → 3-{4-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-methylphenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one

Participants

Reaction Steps

To a mixture of (4-bromo-2-methylphenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (155 mg) described in Preparation Example 118, 1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one (112 mg) described in Preparation Example 54, cesium carbonate (261 mg) and copper(I) iodide (76 mg) were added toluene (10 mL) and N,N′-dimethylethylenediamine (86 μL), and the mixture was stirred with heating under reflux for 19 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-methylphenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one. The obtained 3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-methylphenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one was dissolved in trifluoroacetic acid (3 mL), and the mixture was stirred at room temperature for 22 hr. The solvent was evaporated from the reaction mixture, and 5% aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with chloroform/methanol (10:1). The organic layer was 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 (74 mg).

Provenance & Evidence