Ethanol → 4,4,4-Trifluoro-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-butyronitrile

HRID 1501416Notes

Reaction equation

HRID 1501416 reaction equation
[F:1][C:2]([F:30])([F:29])[CH:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][N:18](COCC[Si](C)(C)C)[C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][C:5]#[N:6].C1COCC1.C([O-])(O)=O.[Na+].C(O)C.[OH-].[NH4+]>Cl.O.C(OCC)(=O)C>[F:30][C:2]([F:1])([F:29])[CH:3]([N:7]1[CH:11]=[C:10]([C:12]2[C:13]3[CH:20]=[CH:19][NH:18][C:14]=3[N:15]=[CH:16][N:17]=2)[CH:9]=[N:8]1)[CH2:4][C:5]#[N:6]

Participants

9

Reactant 5

HCID 702EthanolHCID 8028TetrahydrofuranHCID 14923Ammonium HydroxideHCID 516892Sodium BicarbonateHCID 574776494,4,4-Trifluoro-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]butanenitrile

Product 1

HCID 177542644,4,4-Trifluoro-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-butyronitrileYield 138%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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). 1H NMR (400 MHz, DMSO): δ 12.2 (1H, s); 8.95 (1H, s); 8.7 (1H, s); 8.5 (1H, s); 7.63 (1H, d); 6.96 (1H, d); 6.01 (1H, m); 3.7 (2H, m). MS (M+H): 306.

Workup

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

Sources & evidence

ORD record
ord-38bdb4d71e6e44a588daba4dc2935c42
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

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