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

HRID 1922303Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1922303
[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

Komponenten

8

Edukt 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

Produkt 1

HCID 44124722N-{(2S)-5-[(2-methyl-3-pyridinyl)oxy]-2,3-dihydro-1H-inden-2-yl}-2-propanesulfonamideAusbeute 67,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178419072HCID 178419072, VerbindungKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-40d44f7b08c548b0837f4fec566fe592
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173820B2

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