N,N'-Dimethylethylenediamine → 3-Benzoyl-1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-4-methylimidazolidin-2-one

HRID 2411863Notes

Reaction equation

HRID 2411863 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.[C:25]([N:33]1[CH:37]([CH3:38])[CH2:36][NH:35][C:34]1=[O:39])(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.O.O1CCOCC1>[C:25]([N:33]1[CH:37]([CH3:38])[CH2:36][N:35]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([N:10]3[CH2:15][CH2:14][N:13]([C:16]4[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][N:17]=4)[CH2:12][CH2:11]3)=[O:9])=[C:4]([F:24])[CH:3]=2)[C:34]1=[O:39])(=[O:32])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 58484626(4-Bromo-2-fluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneHCID 712527551-Benzoyl-5-methylimidazolidin-2-one

Product 1

HCID 712526193-Benzoyl-1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3-fluorophenyl}-4-methylimidazolidin-2-oneYield 17%

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-benzoyl-5-methylimidazolidin-2-one (105 mg) described in Preparation Example 56, tripotassium phosphate (170 mg) and copper(I) iodide (76 mg) were added 1,4-dioxane (8 mL) and N,N′-dimethylethylenediamine (86 μL), and the mixture was stirred with heating under reflux for 10 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 the title compound (35 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 10 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-19573af27bcd472b90f5df306fdeef3f
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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