Sodium Bicarbonate → 2-Methyl-5-oxo-4-{3-[3-(trifluoromethyl)phenyl]-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro[3,4-b]-pyridine-3-carbonitrile

HRID 408559Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 408559
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]4[CH2:20][O:21][C:22](=[O:23])[C:12]3=4)[CH:9]=2)[NH:4][N:3]=1.[F:24][C:25]([F:36])([F:35])[C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.C(=O)(O)[O-].[Na+]>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>[CH3:19][C:15]1[NH:14][C:13]2[CH2:20][O:21][C:22](=[O:23])[C:12]=2[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([C:25]([F:36])([F:35])[F:24])[CH:31]=2)[C:16]=1[C:17]#[N:18]

Komponenten

6

Edukt 3

HCID 516892Sodium BicarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 178428406HCID 178428406, Verbindung

Produkt 1

HCID 469113222-Methyl-5-oxo-4-{3-[3-(trifluoromethyl)phenyl]-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro[3,4-b]-pyridine-3-carbonitrileAusbeute 4,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a degassed solution of 120 mg (0.323 mmol) 4-(3-bromo-1H-indazol-5-yl)-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridine-3-carbonitrile (Example 24) and 73.7 mg (0.388 mmol) [3-(trifluoromethyl)phenyl]boronic acid in anhydrous 1,4-dioxane (4.8 ml) were added under argon atmosphere 37.4 mg (0.032 mmol) tetrakis(triphenylphosphine)palladium(0) and aqueous sodium bicarbonate solution (2 M, 0.77 ml). The resulting mixture was stirred at 95° C. for 12 h. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was subsequently washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (first run: acetonitrile/water gradient, final mixture 95:5 v/v; second run: methanol/water isocratic 75:25 v/v) to yield the title compound as a white solid (6 mg, 4% of th.).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was subsequently washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative RP-HPLC (first run: acetonitrile/water gradient, final mixture 95:5 v/v; second run: methanol/water isocratic 75:25 v/v)

Quellen und Nachweise

ORD-Eintrag
ord-3e0d684fdb974ff28817bb57e24e3baf
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759341B2

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