Reacción #73226

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Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Tratamiento posterior

  1. 1
    Temperaturato reflux overnight
  2. 2
    OtroThe solvent was removed by rotary evaporation
  3. 3
    Otroto give a greenish orange oil/glass
  4. 4
    ExtracciónThe aqueous phase was extracted with ethyl acetate
  5. 5
    LavadoThe organic layers were washed with brine
  6. 6
    Otroreduced by rotary evaporation
  7. 7
    Otroto give an oil/glass residue
  8. 8
    OtroThe solvent was removed by rotary evaporation
  9. 9
    Otroto give a pale orange foam/solid
  10. 10
    OtroThe crude was chromatographed with 0-7% MeOH/DCM, 0-0.7% NH4OH

Procedimiento

A solution of 4,4,4-trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile (3.1 g, 0.0071 mol) from Step 1 in THF (35 mL, 0.43 mol) and 3.0 M HCl in water (35 mL) was heated to reflux overnight. The solvent was removed by rotary evaporation to give a greenish orange oil/glass. The oil was stirred with ethyl acetate and sat. NaHCO3 (50 mL). The aqueous phase was extracted with ethyl acetate. The organic layers were washed with brine and reduced by rotary evaporation to give an oil/glass residue. The residue was stirred in ethanol (20 mL, 0.3 mol) and 8.0 M ammonium hydroxide in water (10 mL) over a weekend. The solvent was removed by rotary evaporation to give a pale orange foam/solid. The crude was chromatographed with 0-7% MeOH/DCM, 0-0.7% NH4OH to give 3 g of a pale orange paste/solid. The solid was recrystallized from EtOH to give 1.6 g of an off-white crystals (74% yield).

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US08541425B2uspto-grants-2013_09