N,N'-Dimethylethylenediamine → N-{2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-5-(2-oxoimidazolidin-1-yl)phenyl}-N-methylmethanesulfonamide

HRID 2411945Notes

Reaction equation

HRID 2411945 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][N:23]=3)[CH2:18][CH2:17]2)=[O:15])=[C:6]([N:8]([CH3:13])[S:9]([CH3:12])(=[O:11])=[O:10])[CH:7]=1.C([N:33]1[CH2:37][CH2:36][NH:35][C:34]1=[O:38])(=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>[Cu]I.O.O1CCOCC1>[CH3:28][C:27]1[C:22]([N:19]2[CH2:20][CH2:21][N:16]([C:14]([C:5]3[CH:4]=[CH:3][C:2]([N:33]4[CH2:37][CH2:36][NH:35][C:34]4=[O:38])=[CH:7][C:6]=3[N:8]([CH3:13])[S:9]([CH3:12])(=[O:11])=[O:10])=[O:15])[CH2:17][CH2:18]2)=[N:23][CH:24]=[C:25]([CH3:29])[CH:26]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 79350N-AcetylimidazolidinoneHCID 71252240N-{5-bromo-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-N-methylmethanesulfonamide

Product 1

HCID 71252124N-{2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-5-(2-oxoimidazolidin-1-yl)phenyl}-N-methylmethanesulfonamideYield 60.5%

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 N-{5-bromo-2-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]phenyl}-N-methylmethanesulfonamide (540 mg) described in Preparation Example 227 and 1-acetylimidazolidin-2-one (144 mg), cesium carbonate (731 mg), copper(I) iodide (107 mg) were added dioxane (3 mL) and N,N′-dimethylethylenediamine (121 μL), and the mixture was stirred under refluxing for 8 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was evaporated, methanol (2 mL) and 1N aqueous sodium hydroxide solution (1.7 mL) were added to the obtained residue, and the mixture was stirred at 40° C. for 3 hr. After cooling, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The solvent was evaporated, and the residue was purified by column chromatography (ethyl acetate:methanol) to give the title compound (330 mg).

Workup

  1. temperatureunder refluxing for 8 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. customThe solvent was evaporated
  5. additionmethanol (2 mL) and 1N aqueous sodium hydroxide solution (1.7 mL) were added to the obtained residue
  6. stirringthe mixture was stirred at 40° C. for 3 hr
  7. temperatureAfter cooling
  8. additionwater was added to the reaction mixture
  9. extractionthe mixture was extracted with ethyl acetate
  10. customThe solvent was evaporated
  11. customthe residue was purified by column chromatography (ethyl acetate:methanol)

Sources & evidence

ORD record
ord-4feb6792c0b84094bbbc2f7e2621b66d
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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