Sodium hydride → Tert-butyl 4-((6-(5-(methylsulfonyl)indolin-1-yl)pyrimidin-4-yl)oxy)piperidine-1-carboxylate

HRID 448560

Reaktionsgleichung

Reaktionsgleichung von HRID 448560
[H-].[Na+].[CH3:3][S:4]([C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH2:11][CH2:10]2)(=[O:6])=[O:5].[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[C:34](Cl)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.[Cl-].[Na+].O>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([O:29][C:30]2[CH:35]=[C:34]([N:12]3[C:13]4[C:9](=[CH:8][C:7]([S:4]([CH3:3])(=[O:6])=[O:5])=[CH:15][CH:14]=4)[CH2:10][CH2:11]3)[N:33]=[CH:32][N:31]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 27361365-(Methanesulfonyl)-2,3-dihydro-1H-indoleHCID 21906116tert-Butyl 4-[(6-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate

Produkt 1

HCID 25242414Tert-butyl 4-((6-(5-(methylsulfonyl)indolin-1-yl)pyrimidin-4-yl)oxy)piperidine-1-carboxylateAusbeute 40,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

To a suspension of sodium hydride (0.25 g, 2 eq) in 10 mL of DMF, was added 5-methanesulfonyl-2,3-dihydro-1H-indole (0.63 g, 1 eq). The mixture was stirred at room temperature for 10 minutes then 3a (1 g, 3.19 mmol) was added. The resulting mixture was heated up to 80° C. for 18 h. The reaction mixture was then allowed to cool down to room temperature and brine (200 mL) was added. The solution was extracted with DCM twice (200 mL then 50 mL). The combined extracts were washed with brine (2×50 mL), dried over magnesium sulfate and filtered. The solvent was removed under vacuum to give an oil which was purified by column chromatography (elution with 10-100% ethyl acetate and 0.1% TEA in hexanes) to give 0.61 g of 4a (40% yield), LCMS 475.2 (MH+).

Aufarbeitung

  1. temperatureThe resulting mixture was heated up to 80° C. for 18 h
  2. temperatureto cool down to room temperature
  3. extractionThe solution was extracted with DCM twice (200 mL
  4. washThe combined extracts were washed with brine (2×50 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed under vacuum
  8. customto give an oil which
  9. customwas purified by column chromatography (elution with 10-100% ethyl acetate and 0.1% TEA in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a6d2503a08774c0e9f7736b2e59ee886
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481731B2

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