Potassium Carbonate → (S)-tert-Butyl 4-(1-amino-3-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

HRID 216950

Reaktionsgleichung

Reaktionsgleichung von HRID 216950
[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](B2OC(C)(C)C(C)(C)O2)=[CH:7][CH:6]=1.Br[C:39]1[CH:47]=[C:46]2[C:42]([CH2:43][C:44](=[O:49])[N:45]2[CH3:48])=[CH:41][CH:40]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH2:1][C:2](=[O:37])[C@@H:3]([NH:20][C:21]([C:23]1([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)=[O:22])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:39]2[CH:47]=[C:46]3[C:42]([CH2:43][C:44](=[O:49])[N:45]3[CH3:48])=[CH:41][CH:40]=2)=[CH:7][CH:6]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 580060486-Bromo-1-methylindolin-2-oneHCID 59568592(S)-tert-Butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Produkt 1

HCID 59568615(S)-tert-Butyl 4-(1-amino-3-(4-(1-methyl-2-oxoindolin-6-yl)phenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamateAusbeute 21,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A solution of (S)-tert-butyl 4-(1-amino-1-oxo-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (Example 16, step (i), 200 mg) and 6-bromo-1-methylindolin-2-one (87 mg) in acetonitrile (5 mL) was treated with potassium carbonate (107 mg) and purged with nitrogen. 1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (15 mg) was added and the reaction stirred is under reflux under nitrogen for 4 h and then evaporated in vacuo. The residue was partitioned between water (40 mL) and ethyl acetate (40 mL). The aqueous was further extracted with ethyl acetate (40 mL) and the combined organic extracts were dried over magnesium sulfate and evaporated in vacuo. The crude product was purified by flash silica chromatography eluting with ethyl acetate. Pure fractions were evaporated to dryness to afford the sub-titled compound (45 mg).

Aufarbeitung

  1. custompurged with nitrogen
  2. addition1,1 bis(Di-tert-butylphosphino)ferrocene palladium dichloride (15 mg) was added
  3. temperatureunder reflux under nitrogen for 4 h
  4. customevaporated in vacuo
  5. customThe residue was partitioned between water (40 mL) and ethyl acetate (40 mL)
  6. extractionThe aqueous was further extracted with ethyl acetate (40 mL)
  7. dry with materialthe combined organic extracts were dried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash silica chromatography
  10. washeluting with ethyl acetate
  11. customPure fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-280a24705fce4a63a39b00de3ffbce0a
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193239B2

Verknüpfte Notizen

Wird geladen…