(Z)-3-cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)acrylonitrile → (2Z)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]acrylonitrile

HRID 1426527Notes

Reaction equation

HRID 1426527 reaction equation
[CH:1]1(/[C:6](/[N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][N:21](COCC[Si](C)(C)C)[C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)=[CH:7]/[C:8]#[N:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH:1]1(/[C:6](/[N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][NH:21][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)=[CH:7]/[C:8]#[N:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 1

HCID 57477618(Z)-3-cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)acrylonitrile

Product 1

HCID 57477617(2Z)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]acrylonitrileYield 76%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (2Z)-3-cyclopentyl-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]acrylonitrile (0.030 g, 0.069 mol) in DCM (3 mL) and TFA (2 mL) was stirred for 1 hour. The solvents were removed in vacuo and the product was stirred with THF (1.5 mL), sodium hydroxide, 50% aqueous solution (0.75 mL) and water (0.75 mL) for 2 hours. The reaction mixture was neutralized by the dropwise addition of conc. HCl. The product was extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by preparative-HPLC/MS (C18 column eluting with a gradient of ACN/H2O containing 0.15% NH4OH) to afford the desired product (16 mg, 76%).

Workup

  1. customThe solvents were removed in vacuo
  2. additionThe reaction mixture was neutralized by the dropwise addition of conc. HCl
  3. extractionThe product was extracted with ethyl acetate
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by preparative-HPLC/MS (C18 column
  8. washeluting with a gradient of ACN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-89c6048610284b159a721480842475ac
Source dataset
uspto-grants-2015_01
Patent number
US08933086B2

Reaction notes

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