Cesium carbonate → 2-Cyclopropyl-1-({5-[2-fluoro-5-(trifluoromethyl)phenyl]-2-furanyl}methyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 913752

Reaktionsgleichung

Reaktionsgleichung von HRID 913752
Br[C:2]1[O:6][C:5]([CH2:7][N:8]2[C:16]3[C:11](=[C:12]([C:19]([F:22])([F:21])[F:20])[C:13]([C:17]#[N:18])=[CH:14][CH:15]=3)[CH:10]=[C:9]2[CH:23]2[CH2:25][CH2:24]2)=[CH:4][CH:3]=1.C([O-])(=O)C.[K+].CC1C(C)OB(B2OC(C)C(C)O2)O1.Br[C:46]1[CH:51]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:49]=[CH:48][C:47]=1[F:56].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[CH:23]1([C:9]2[N:8]([CH2:7][C:5]3[O:6][C:2]([C:46]4[CH:51]=[C:50]([C:52]([F:54])([F:55])[F:53])[CH:49]=[CH:48][C:47]=4[F:56])=[CH:3][CH:4]=3)[C:16]3[C:11]([CH:10]=2)=[C:12]([C:19]([F:22])([F:21])[F:20])[C:13]([C:17]#[N:18])=[CH:14][CH:15]=3)[CH2:25][CH2:24]1

Komponenten

9

Edukt 5

HCID 10796Cesium carbonateHCID 1442953-Bromo-4-fluorobenzotrifluorideHCID 517044Potassium AcetateHCID 101980872-(4,5-Dimethyl-1,3,2-dioxaborolan-2-yl)-4,5-dimethyl-1,3,2-dioxaborolaneHCID 674049931-[(5-Bromo-2-furanyl)methyl]-2-cyclopropyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Produkt 1

HCID 866207162-Cyclopropyl-1-({5-[2-fluoro-5-(trifluoromethyl)phenyl]-2-furanyl}methyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrileAusbeute 1,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of (1-[(5-bromo-2-furanyl)methyl]-2-cyclopropyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 310C) (0.1 g, 0.24 mmol) in dry DMF (5 mL) was added potassium acetate (0.072 g, 0.73 mmol), palladium acetate (0.011 g, 0.048 mmol) and 4,4′,5,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborolane (0.068 g, 0.264 mmol). The reaction is heated to 90° C. for 3 h. To the reaction was then added 2-bromo-1-fluoro-4-(trifluoromethyl)benzene (0.119 g, 0.48 mmol), cesium carbonate (0.159 g, 0.48 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.057 g, 0.048 mmol). The mixture was stirred at 85° C. overnight. Solids were filtered and the filtrate was then concentrated in vacuo. The residue was purified by radial chromatography (0-40% EtOAc-hexanes gradient) and by semipreparative HPLC to afford the title compound (0.002 g, 1.3% yield): MS (ES) m/z 493 (M+1).

Aufarbeitung

  1. filtrationSolids were filtered
  2. concentrationthe filtrate was then concentrated in vacuo
  3. customThe residue was purified by radial chromatography (0-40% EtOAc-hexanes gradient) and by semipreparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-e0d71a724f984ab981f82d20cae440cb
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026262B2

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