Sodium Carbonate → (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl) oxazolidin-2-one

HRID 539104Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 539104
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:22][CH3:23])[CH2:14][O:13][C:12]3=[O:24])=[N:7][C:6]=12.[F:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]=1[C:41]1[N:45]=[CH:44][N:43]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[N:42]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[F:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@@H:15]([C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=5[O:22][CH3:23])[CH2:14][O:13][C:12]4=[O:24])=[N:7][C:6]=23)[CH:29]=[CH:28][C:27]=1[C:41]1[N:45]=[CH:44][N:43]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[N:42]=1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034012HCID 67034012, VerbindungHCID 67034207(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl)oxazolidin-2-one

Produkt 1

HCID 68088961(S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl) oxazolidin-2-oneAusbeute 53,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a round bottom flask were added (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl)oxazolidin-2-one (0.103 g, 0.265 mmol), 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (0.144 g, 0.344 mmol), dioxane (2 mL) and 2.0 M Na2CO3 (0.40 mL, 0.80 mmol). The mixture was degassed by bubbling N2 through the solution. Pd2 dba3 (0.012 g, 0.013 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.013 g, 0.027 mmol) were added, and the mixture was heated at 80° C. overnight. The reaction mixture was cooled to ambient temperature, diluted with H2O, and extracted thoroughly with EtOAc and DCM. The combined organic extracts were washed with brine, dried, and concentrated. Purification of the crude material on silica, eluting with 70% EtOAc/hexanes, to provide (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl)oxazolidin-2-one as a bright yellow solid (0.0848 g, 53%). MS (APCI+) m/z 601 [M+H]+.

Aufarbeitung

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. extractionextracted thoroughly with EtOAc and DCM
  5. washThe combined organic extracts were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customPurification of the crude material on silica
  9. washeluting with 70% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-ae209cd93a9e467fb6331395c0cffcaf
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865726B2

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