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Potassium Carbonate → tetraisopropyl(2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)

HRID 2410256
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2410256
Br[C:2]1[CH:3]=[C:4]([CH2:8][C:9]([P:21](=[O:30])([O:26][CH:27]([CH3:29])[CH3:28])[O:22][CH:23]([CH3:25])[CH3:24])([P:11](=[O:20])([O:16][CH:17]([CH3:19])[CH3:18])[O:12][CH:13]([CH3:15])[CH3:14])[F:10])[CH:5]=[N:6][CH:7]=1.[NH:31]1[C:39]2[C:34](=[CH:35][C:36](B(O)O)=[CH:37][CH:38]=2)[CH:33]=[N:32]1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[NH:31]1[C:39]2[C:34](=[CH:35][C:36]([C:2]3[CH:3]=[C:4]([CH2:8][C:9]([P:11](=[O:20])([O:16][CH:17]([CH3:19])[CH3:18])[O:12][CH:13]([CH3:14])[CH3:15])([P:21](=[O:30])([O:22][CH:23]([CH3:25])[CH3:24])[O:26][CH:27]([CH3:29])[CH3:28])[F:10])[CH:5]=[N:6][CH:7]=3)=[CH:37][CH:38]=2)[CH:33]=[N:32]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 177505041H-Indazole-5-boronic acidHCID 86691496Tetraisopropyl(2-(5-bromopyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)

Produkt 1

HCID 86691495tetraisopropyl(2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate)Ausbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397
HCID 178418397, Verbindung
Katalysator
HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Tetraisopropyl (2-(5-bromopyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate) (85 mg; 0.16 mmol), Pd(PPh3)4 (36.9 mg; 0.032 mmol) and (1H-indazol-5-yl)boronic acid (39 mg; 0.24 mmol) are added to the vial and the vial is capped with a septum. DME (4 mL) is added and the vial is flushed with argon, an aqueous solution of potassium carbonate (2.5 eq.) is added and the mixture is flushed again with argon. The reaction mixture is stirred at 80° C. for 36 h under an atmosphere of argon. The mixture was cooled to RT, diluted with EtOAc and filtered through Celite™, the Celite™ is washed three times with EtOAc/MeOH (1:1). The filtrate is deposited on silica gel and purified by column chromatography (on pre washed silica with 1% NEt3 in hexanes) using a solvent gradient from hexanes to EtOAc and then to 50% MeOH in EtOAc. The pure product is isolated as a brown oil (41 mg, 45% yield).

Aufarbeitung

  1. customis capped with a septum
  2. customthe vial is flushed with argon
  3. customthe mixture is flushed again with argon
  4. temperatureThe mixture was cooled to RT
  5. additiondiluted with EtOAc
  6. filtrationfiltered through Celite™
  7. washthe Celite™ is washed three times with EtOAc/MeOH (1:1)
  8. custompurified by column chromatography (on pre washed silica with 1% NEt3 in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-71ba16d3ec9e42a0bb8259ab96059151
Quelldatensatz
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08816082B2

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