Sodium Carbonate → (S)-4-(3-chlorophenyl)-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)oxazolidin-2-one

HRID 539117Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 539117
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]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][O:13][C:12]3=[O:23])=[N:7][C:6]=12.[F:24][C:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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].O.CCOC(C)=O.O1CCOCC1>[Cl:22][C:18]1[CH:17]=[C:16]([C@H:15]2[CH2:14][O:13][C:12](=[O:23])[N:11]2[C:8]2[CH:9]=[CH:10][N:5]3[N:4]=[CH:3][C:2]([C:29]4[CH:28]=[CH:27][C:26]([C:40]5[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:51])([CH3:50])[CH3:52])[N:41]=5)=[C:25]([F:24])[CH:30]=4)=[C:6]3[N:7]=2)[CH:21]=[CH:20][CH:19]=1

Komponenten

9

Edukt 4

HCID 10340Sodium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67034012HCID 67034012, VerbindungHCID 67034388(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(3-chlorophenyl)oxazolidin-2-one

Produkt 1

HCID 68088957(S)-4-(3-chlorophenyl)-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)oxazolidin-2-oneAusbeute 43,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(3-chlorophenyl)oxazolidin-2-one (100 mg, 0.254 mmol) were added 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 (139 mg, 0.330 mmol), Pd2 dba3 (11.6 mg, 0.0127 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (14.7 mg, 0.0254 mmol), dioxane (1.2 mL) and 2M Na2CO3 (0.2 mL). The reaction was stirred for 2 hours at 80° C. in a sealed tube. After cooling, EtOAc and water were added. The organic phase was washed with brine and dried over MgSO4. The residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes) to yield (S)-4-(3-chlorophenyl)-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)oxazolidin-2-one (67 mg, 43.5% yield) as a pale yellow solid.

Aufarbeitung

  1. temperatureAfter cooling
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. customThe residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes)

Quellen und Nachweise

ORD-Eintrag
ord-c9425ee2654b4b15bd1ba189fb43ca7d
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865726B2

Notizen zur Reaktion

Wird geladen…