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

HRID 2411854Notes

Reaction equation

HRID 2411854 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[C:4]([F:24])[CH:3]=1.[CH3:25][O:26][C:27]1[CH:41]=[CH:40][C:30]([CH2:31][N:32]2[CH2:36][C:35]([CH3:38])([CH3:37])[NH:34][C:33]2=[O:39])=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>[Cu]I.O.O1CCOCC1>[CH3:22][C:21]1[C:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:34]4[C:35]([CH3:38])([CH3:37])[CH2:36][N:32]([CH2:31][C:30]5[CH:40]=[CH:41][C:27]([O:26][CH3:25])=[CH:28][CH:29]=5)[C:33]4=[O:39])=[CH:3][C:4]=3[F:24])=[O:9])[CH2:11][CH2:12]2)=[N:17][CH:18]=[C:19]([CH3:23])[CH:20]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 58484626(4-Bromo-2-fluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneHCID 712526731-(4-Methoxybenzyl)-4,4-dimethylimidazolidin-2-one

Product 1

HCID 712522423-{4-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-1-(4-methoxybenzyl)-4,4-dimethylimidazolidin-2-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 32 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was evaporated
  8. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-201c0fcd5dbe43f1b0411d3432c70fa7
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

Loading…