N,N-Dimethylglycine → N-{(2S)-5-[(2-methyl-3-pyridinyl)oxy]-2,3-dihydro-1H-inden-2-yl}-2-propanesulfonamide

HRID 1922303Notes

Reaction equation

HRID 1922303 reaction equation
[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[CH2:21][C@H:20]([NH:25][S:26]([CH:29]([CH3:31])[CH3:30])(=[O:28])=[O:27])[CH2:19]2.CN(C)CC(O)=O>CS(C)=O.C(OCC)(=O)C.[Cu-]=O>[CH3:1][C:2]1[C:7]([O:8][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[CH2:21][C@H:20]([NH:25][S:26]([CH:29]([CH3:31])[CH3:30])(=[O:27])=[O:28])[CH2:19]3)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 707192-Methylpyridin-3-olHCID 46899974(S)-N-(5-bromo-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

Product 1

HCID 44124722N-{(2S)-5-[(2-methyl-3-pyridinyl)oxy]-2,3-dihydro-1H-inden-2-yl}-2-propanesulfonamideYield 67.6%

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-methyl-3-pyridinol (8.57 g, 79 mmol), cesium carbonate (51.2 g, 157 mmol) and copper (I) oxide (11.24 g, 79 mmol) in dimethyl sulfoxide (250 mL) was stirred for 5 minutes at room temperature. N-[(2S)-5-bromo-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide (25 g, 79 mmol, Description 1) was added followed by N,N-dimethylglycine (8.10 g, 79 mmol). The reaction was heated at 130° C. overnight. The reaction was allowed to reach room temperature and diluted with ethyl acetate (500 ml) then filtered through celite washing with ethyl acetate. The organic phase was washed with water (2×500 ml), dried over Na2SO4 and concentrated in vacuo. This material was purified using Biotage 75 L eluting with cyclohexane/ethyl acetate 2/8 to give N-{(2S)-5-[(2-methyl-3-pyridinyl)oxy]-2,3-dihydro-1H-inden-2-yl}-2-propanesulfonamide (free base, 18.5 g).

Workup

  1. temperatureThe reaction was heated at 130° C. overnight
  2. customto reach room temperature
  3. filtrationthen filtered
  4. washthrough celite washing with ethyl acetate
  5. washThe organic phase was washed with water (2×500 ml)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThis material was purified
  9. washeluting with cyclohexane/ethyl acetate 2/8

Sources & evidence

ORD record
ord-40d44f7b08c548b0837f4fec566fe592
Source dataset
uspto-grants-2012_05
Patent number
US08173820B2

Reaction notes

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