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

HRID 2411857Notes

Reaction equation

HRID 2411857 reaction equation
[CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[C:27]([CH3:29])([CH3:28])[CH2:26][N:25](CC5C=CC(OC)=CC=5)[C:24]4=[O:39])=[CH:19][C:18]=3[CH3:40])=[O:16])[CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1>FC(F)(F)C(O)=O>[CH3:1][C:2]1[C:3]([N:9]2[CH2:10][CH2:11][N:12]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[C:27]([CH3:28])([CH3:29])[CH2:26][NH:25][C:24]4=[O:39])=[CH:19][C:18]=3[CH3:40])=[O:16])[CH2:13][CH2:14]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

3

Reactant 1

HCID 712522783-{4-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-methylphenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one

Product 1

HCID 712526251-{4-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-methylphenyl}-5,5-dimethylimidazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

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).

Workup

  1. customThe solvent was evaporated from the reaction mixture, and 5% aqueous sodium hydrogen carbonate solution
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with chloroform/methanol (10:1)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:methanol)

Sources & evidence

ORD record
ord-d2199cdcc2024401a66efb65ba5e9c47
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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