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Potassium Phosphate, Tribasic → 6-(2-Ethyl-5-fluoro-4-methoxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole

HRID 340068
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 340068
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1.[CH2:17]([C:19]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([F:27])=[CH:21][C:20]=1B1OC(C)(C)C(C)(C)O1)[CH3:18].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:17]([C:19]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([F:27])=[CH:21][C:20]=1[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:4][CH:3]=1)[CH3:18]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 672932406-bromo-1-(oxan-2-yl)-1H-indazoleHCID 712380622-(2-Ethyl-5-fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Produkt 1

HCID 712379806-(2-Ethyl-5-fluoro-4-methoxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazoleAusbeute 71,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704
Tetrakis(triphenylphosphine)palladium
Katalysator
HCID 962WaterLösungsmittel
HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a solution of 6-bromo-1-(tetrahydro-pyran-2-yl)-1H-indazole (WO 2010/027500, 2.25 g, 8.0 mmol) and 2-(2-ethyl-5-fluoro-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Preparation 13, 2.24 g, 8.0 mmol) in dioxane (32 mL) was added potassium phosphate (5.1 g, 24 mmol) as a solution in water (8 mL). The reaction mixture was degassed with nitrogen and treated with tetrakis (triphenylphosphine) palladium(0) (1.85 g, 1.6 mmol). The reaction mixture was heated at 110° C. for 18 hours, cooled to room temperature and filtered through a pad of Arbocel®, washing with EtOAc (2×100 mL). The filtrate was washed with water (100 mL), dried over MgSO4 and concentrated in vacuo. The crude material was purified by column chromatography on silica gel eluting with 10% EtOAc in heptane to give the title compound as a white solid (2.024 g) in a 71% yield.

Aufarbeitung

  1. customThe reaction mixture was degassed with nitrogen
  2. temperaturecooled to room temperature
  3. filtrationfiltered through a pad of Arbocel®
  4. washwashing with EtOAc (2×100 mL)
  5. washThe filtrate was washed with water (100 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by column chromatography on silica gel eluting with 10% EtOAc in heptane

Quellen und Nachweise

ORD-Eintrag
ord-6ddaf6549133401f8b714fc35d9dc855
Quelldatensatz
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08895544B2

Notizen zur Reaktion

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