Cesium fluoride → 1-({5-[3,5-bis(Trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}methyl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1188651

Reaktionsgleichung

Reaktionsgleichung von HRID 1188651
Cl[C:2]1[S:6][N:5]=[C:4]([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[CH3:23])[N:3]=1.[F:24][C:25]([F:40])([F:39])[C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1.[F-].[Cs+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:24][C:25]([F:39])([F:40])[C:26]1[CH:27]=[C:28]([C:2]2[S:6][N:5]=[C:4]([CH2:7][N:8]3[C:16]4[C:11](=[C:12]([C:19]([F:22])([F:21])[F:20])[C:13]([C:17]#[N:18])=[CH:14][CH:15]=4)[CH:10]=[C:9]3[CH3:23])[N:3]=2)[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=1

Komponenten

6

Edukt 3

HCID 25953Cesium fluorideHCID 1562653,5-Bis-trifluoromethylphenylboronic acidHCID 674050131-[(5-Chloro-1,2,4-thiadiazol-3-yl)methyl]-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Produkt 1

HCID 866207091-({5-[3,5-bis(Trifluoromethyl)phenyl]-1,2,4-thiadiazol-3-yl}methyl)-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrileAusbeute 40,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 10974057(Butane-1,4-diyl)bis(diphenylphosphane)--dichloropalladium (1/1)KatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of 1-[(5-chloro-1,2,4-thiadiazol-3-yl)methyl]-2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 326) (0.1 g, 0.28 mmol) in dry DME (3 mL) were added [3,5-bis(trifluoromethyl)phenyl]boronic acid (0.145 g, 0.56 mmol), cesium fluoride (0.13 g, 0.84 mmol) and [1,4-bis(diphenylphosphino)butane]palladium(II) dichloride (0.1 g, 0.17 mmol). The mixture was stirred at 90° C. in a sealed tube overnight. Solid was filtered and the filtrate was then concentrated in vacuo. The residue was purified by radial chromatography (0-50% EtOAc-hexanes gradient) to afford the title compound (0.06 g, 40% yield): 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 2H), 8.04 (s, 1H), 7.67 (d, J=8.4 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.66 (s, 1H), 5.65 (s, 2H), 2.67 (s, 3H); MS (ES) m/z 533 (M−1).

Aufarbeitung

  1. filtrationSolid was filtered
  2. concentrationthe filtrate was then concentrated in vacuo
  3. customThe residue was purified by radial chromatography (0-50% EtOAc-hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-1651b8a6bc2144c8b7e8abfcd42cf6e3
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673948B2

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