Hydrochloric Acid → 4-(1H-pyrazol-4-yl)-5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

HRID 1617373Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1617373
[F:1][C:2]1[C:3](I)=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.C(OC([N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1)C)C.C(=O)([O-])[O-].[Na+].[Na+].Cl.[OH-].[Na+]>O1CCOCC1.O.CCOC(C)=O.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.C1COCC1>[NH:25]1[CH:29]=[C:28]([C:3]2[C:2]([F:1])=[CH:7][N:6]=[C:5]3[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:10][C:4]=23)[CH:27]=[N:26]1

Komponenten

11

Edukt 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 467367981-(1-Ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 584313555-fluoro-4-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine

Produkt 1

HCID 584313954-(1H-pyrazol-4-yl)-5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridineAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of 5-fluoro-4-iodo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (7.20 g, 18.4 mmol), 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.36 g, 20.1 mmol), tetrakis(triphenylphosphine)palladium(0) (1.06 g, 0.918 mmol) and sodium carbonate (5.84 g, 55.1 mmol) in 1,4-dioxane (50 mL) and water (25 mL) was stirred at 110° C. under nitrogen for 1 hour. After being cooled to room temperature, the mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatograpgy on silica gel eluting with 10-30% EtOAc/hexanes. The purified intermediate was added into a mixture solution of THF (8.0 mL), water (30 mL) and hydrogen chloride (30 mL, 100 mmol). The resulting suspension was stirred at room temperature for 2 hours. The mixture was adjusted to pH=9-10 with 6 N NaOH and extracted with EtOAc (2×). The combined extracts were washed with water, brine and dried over anhydrous Na2SO4. After filtration and concentration, the residue was added into a mixture solvents of hexane and EtOAc (9/1, 50 mL). The solid formed was filtered to give 4.2 g (69%) of 4-(1H-pyrazol-4-yl)-5-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine as a light green solid. LC/MS found: 333.2 (M+H)+.

Aufarbeitung

  1. temperatureAfter being cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatograpgy on silica gel eluting with 10-30% EtOAc/hexanes
  6. stirringThe resulting suspension was stirred at room temperature for 2 hours
  7. extractionextracted with EtOAc (2×)
  8. washThe combined extracts were washed with water, brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationAfter filtration and concentration
  11. additionthe residue was added into a mixture solvents of hexane and EtOAc (9/1, 50 mL)
  12. customThe solid formed
  13. filtrationwas filtered

Quellen und Nachweise

ORD-Eintrag
ord-81f874b09d594f40a4153014975954ef
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765734B2

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