Sodium Carbonate → 5-[3-Chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1-(4-fluorophenyl)-1H-pyrazol-3-ylamine

HRID 83555Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 83555
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](I)=[CH:11][C:10]([NH2:14])=[N:9]2)=[CH:4][CH:3]=1.[Cl:15][C:16]1[CH:17]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:28])([F:27])[F:26])[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[C:10]([NH2:14])[CH:11]=2)[CH:19]=[C:20]([CH2:22][O:23][C@H:24]([CH3:29])[C:25]([F:26])([F:27])[F:28])[CH:21]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 71287834HCID 71287834, VerbindungHCID 86680375HCID 86680375, Verbindung

Produkt 1

HCID 712878655-[3-Chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-1-(4-fluorophenyl)-1H-pyrazol-3-ylamineAusbeute 115,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

To a solution of 1-(4-fluorophenyl)-5-iodo-1H-pyrazol-3-ylamine (50 mg) prepared according to the same procedures as Preparation 18 in 1,2-dimethoxyethane (0.5 ml) were sequentially added 2-[3-chloro-5-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (72 mg) prepared according to the same procedures as Preparation 22, a 2M aqueous solution of sodium carbonate (0.25 ml), tricyclohexylphosphine (9.3 mg) and palladium (II) acetate (3.7 mg) at room temperature, and the mixture was stirred at 100° C. for 2 hours. This reaction mixture was cooled to room temperature, filtered through Celite, and subjected to elution with ethyl acetate. The filtrate was extracted with ethyl acetate, the resulting organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1) to give the titled compound (79 mg).

Aufarbeitung

  1. customprepared
  2. customaccording to the same procedures as Preparation 22
  3. filtrationfiltered through Celite
  4. washsubjected to elution with ethyl acetate
  5. extractionThe filtrate was extracted with ethyl acetate
  6. washthe resulting organic layer was washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/1)

Quellen und Nachweise

ORD-Eintrag
ord-7c484ac6613c4ebead43f7c570939f8f
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846746B2

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