N,N'-Dimethylethylenediamine → HCID 71252211, compound

HRID 2411859Notes

Reaction equation

HRID 2411859 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])=[CH:4][CH:3]=1.[CH3:24][O:25][C:26]1[CH:41]=[CH:40][C:29]([CH2:30][N:31]2[C:35](=[O:36])[C:34]([CH3:38])([CH3:37])[NH:33][C:32]2=[O:39])=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>[Cu]I.O.C1(C)C=CC=CC=1>[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:33]4[C:34]([CH3:37])([CH3:38])[C:35](=[O:36])[N:31]([CH2:30][C:29]5[CH:40]=[CH:41][C:26]([O:25][CH3:24])=[CH:27][CH:28]=5)[C:32]4=[O:39])=[CH:3][CH:4]=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 21700179HCID 21700179, compoundHCID 71252046(4-Bromophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

Product 1

HCID 71252211HCID 71252211, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a mixture of (4-bromophenyl) [4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (150 mg) described in Preparation Example 165, 3-(4-methoxybenzyl)-5,5-dimethylimidazolidine-2,4-dione (119 mg) described in Preparation Example 53, cesium carbonate (260 mg) and copper(I) iodide (38 mg) were added toluene (8 mL) and N,N′-dimethylethylenediamine (43 μL), and the mixture was stirred with heating under reflux for 29 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 1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-3-(4-methoxybenzyl)-5,5-dimethylimidazolidine-2,4-dione. The obtained 1-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-3-(4-methoxybenzyl)-5,5-dimethylimidazolidine-2,4-dione was dissolved in 1,2-dichloroethane (4 mL), trifluoromethanesulfonic acid (92 μL) was added and the mixture was stirred at 80° C. for 13 hr. To the reaction mixture was added 5% aqueous sodium hydrogen carbonate solution, 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 (34 mg).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 29 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-44d01cf51e5c4d44b663ad532844b3c9
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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