Trifluoroacetic acid → 1-(2-Cyano-1-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]ethyl)cyclopropanecarbonitrile trifluoroacetate salt

HRID 1962815Notes

Reaction equation

HRID 1962815 reaction equation
[C:1]([CH2:3][CH:4]([C:27]1([C:30]#[N:31])[CH2:29][CH2:28]1)[N:5]1[CH:9]=[C:8]([C:10]2[C:11]3[CH:18]=[CH:17][N:16](COCC[Si](C)(C)C)[C:12]=3[N:13]=[CH:14][N:15]=2)[CH:7]=[N:6]1)#[N:2].[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33]>C(Cl)Cl>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[C:1]([CH2:3][CH:4]([C:27]1([C:30]#[N:31])[CH2:29][CH2:28]1)[N:5]1[CH:9]=[C:8]([C:10]2[C:11]3[CH:18]=[CH:17][NH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:7]=[N:6]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66597812HCID 66597812, compound

Product 1

HCID 665976721-(2-Cyano-1-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]ethyl)cyclopropanecarbonitrile trifluoroacetate saltYield 43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-{2-cyano-1-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]ethyl}cyclopropanecarbonitrile (48 mg, 0.11 mmol) was stirred in a mixture of DCM (3 mL) and TFA (2 mL) for 3 hours. The solvents were removed in vacuo and the residue was re-dissolved in THF (3 mL). 6N NaOH (2 mL) was added and the resulting mixture was stirred at ambient temperature for 3 hours. The crude reaction mixture was partitioned between ethyl acetate and water. The layers were separated and the organic layer was dried over sodium sulfate and the solvent was removed in vacuo. Purification via preparative-HPLC/MS (C18 eluting with a gradient of H2O and ACN containing 0.1% TFA) afforded product (20 mg, 43%).

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutionthe residue was re-dissolved in THF (3 mL)
  3. addition6N NaOH (2 mL) was added
  4. customThe crude reaction mixture
  5. customwas partitioned between ethyl acetate and water
  6. customThe layers were separated
  7. dry with materialthe organic layer was dried over sodium sulfate
  8. customthe solvent was removed in vacuo
  9. customPurification via preparative-HPLC/MS (C18
  10. washeluting with a gradient of H2O and ACN containing 0.1% TFA)

Sources & evidence

ORD record
ord-88c7fe7688b14d3190ca7d049740876f
Source dataset
uspto-grants-2013_04
Patent number
US08415362B2

Reaction notes

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