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

HRID 2411861Notes

Reaction equation

HRID 2411861 reaction equation
Br[C:2]1[N: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])=[CH:4][CH:3]=1.C([N:32]1[CH:36]([CH3:37])[CH2:35][NH:34][C:33]1=[O:38])(=O)C1C=CC=CC=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:4]=[CH:3][C:2]([N:34]4[CH2:35][CH:36]([CH3:37])[NH:32][C:33]4=[O:38])=[N:7][CH:6]=3)=[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 58484661(6-Bromopyridin-3-yl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanoneHCID 712527551-Benzoyl-5-methylimidazolidin-2-one

Product 1

HCID 712519251-{5-[4-(3,5-Dimethylpyridin-2-yl)piperazine-1-carbonyl]pyridin-2-yl}-4-methylimidazolidin-2-oneYield 43.1%

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 (6-bromopyridin-3-yl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (150 mg) described in Preparation Example 127, 1-benzoyl-5-methylimidazolidin-2-one (105 mg) described in Preparation Example 56, cesium carbonate (260 mg) and copper(I) iodide (38 mg) were added 1,4-dioxane (8 mL) and N,N′-dimethylethylenediamine (43 μL), and the mixture was stirred with heating under reflux for 18 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 (68 mg) produced by debenzoylation that simultaneously proceeded during the reaction.

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 18 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-dd22a24381e74f928221f527cd1adf2d
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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