Potassium Fluoride → 2-Cyclopropyl-4-(trifluoromethyl)-1-({5-[3-(trifluoromethyl)phenyl]-2-furanyl}methyl)-1H-indole-5-carbonitrile

HRID 913699

Reaktionsgleichung

Reaktionsgleichung von HRID 913699
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.[F:26][C:27]([F:38])([F:37])[C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.[F-].[K+]>O1CCOCC1.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:32]4[CH:31]=[CH:30][CH:29]=[C:28]([C:27]([F:38])([F:37])[F:26])[CH:33]=4)=[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

6

Edukt 3

HCID 522689Potassium FluorideHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 674049931-[(5-Bromo-2-furanyl)methyl]-2-cyclopropyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Produkt 1

HCID 866206962-Cyclopropyl-4-(trifluoromethyl)-1-({5-[3-(trifluoromethyl)phenyl]-2-furanyl}methyl)-1H-indole-5-carbonitrileAusbeute 32,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of (1-[(5-bromo-2-furanyl)methyl]-2-cyclopropyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 310C) (0.05 g, 0.12 mmol) in dry dioxane (3 mL) were added [3-(trifluoromethyl)phenyl]boronic acid (0.046 g, 0.24 mmol), potassium fluoride (0.021 g, 0.36 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.028 g, 0.024 mmol). The mixture was stirred at 100° C. in a sealed tube 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 recrystallized by methanol to afford the title compound (0.0185 g, 32% yield): 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.69 (d, J=4.9 Hz, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.54 (d, J=8.5 Hz, 1H), 7.51 (m, 1H), 7.38 (m, 1H), 6.63 (d, J=3.4 Hz, 1H), 6.46 (s, 1H), 6.24 (d, J=3.4 Hz, 1H), 5.52 (s, 2H), 2.04 (m, 1H), 1.14 (m, 2H), 0.89 (m, 2H); MS (ES) m/z 475 (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)
  4. customrecrystallized by methanol

Quellen und Nachweise

ORD-Eintrag
ord-dadb1ebf58204c3baa9f3667a7c74dcb
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026262B2

Verknüpfte Notizen

Wird geladen…