Dimethyl Sulfoxide → (4-(1-(2-Cyano-1-cyclopentylethyl)-1h-pyrazol-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate

HRID 1467475Notes

Reaction equation

HRID 1467475 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]([CH2:24]OCC[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.[CH:32]1([CH:37]=CC#N)[CH2:36]CC[CH2:33]1.CS(C)=O.[C:45](=[O:48])([O-])[O-:46].[K+].[K+]>>[C:45]([O:46][CH2:24][N:21]1[C:17]2[N:18]=[CH:19][N:20]=[C:15]([C:13]3[CH:12]=[N:11][N:10]([CH:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:7][C:8]#[N:9])[CH:14]=3)[C:16]=2[CH:23]=[CH:22]1)(=[O:48])[C:32]([CH3:37])([CH3:36])[CH3:33]

Participants

5

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 534011163-Cyclopentylprop-2-enenitrileHCID 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 59420158(4-(1-(2-Cyano-1-cyclopentylethyl)-1h-pyrazol-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalateYield 547.3%

Procedure

To a stirred suspension of [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (19, 158 mg, 0.50 mmol) and 3-cyclopentylacrylonitrile (8, 122 mg, 1.0 mmol, 2.0 equiv) in dimethyl sulfoxide (DMSO, 1.0 mL, 14 mmol) at room temperature was added powder potassium carbonate (K2CO3, 10.4 mg, 0.075 mmol, 0.15 equiv). The reaction mixture was then stirred at room temperature for 5 h. The reaction mixture became a clear solution in 2 h. When LCMS showed the reaction was deemed complete, the reaction was quenched with water (H2O, 5 mL) and extracted with ethyl acetate (EtOAc, 3×15 mL). The combined organic extracts were washed with saturated aqueous NaCl solution (10 mL), dried over magnesium sulfate (MgSO4), and concentrated under reduced pressure. The residue was then purified by flash chromatography (SiO2, 0-50% EtOAc/hexanes gradient elution) to afford racemic (4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (20, 172.6 mg, 210 mg theoretical, 82% yield) as a white solid. For 20: 1H NMR (CDCl3, 400 MHz) δ ppm 8.87 (s, 1H), 8.30 (s, 1H), 8.29 (s, 1H), 7.47 (d, 1H, J=3.9 Hz), 6.75 (d, 1H, J=3.9 Hz), 6.24 (s, 2H), 4.25 (m, 1H), 3.12 (dd, 1H, J=17.0, 8.7 Hz), 2.95 (dd, 1H, J=17.0, 3.9 Hz), 2.58 (m, 1H), 1.95 (m, 1H), 1.72-1.52 (m, 5H), 1.25 (m, 2H), 1.14 (s, 9H); C23H28N6O2 (MW, 420.51), LCMS (EI) m/e 421.4 (M++H).

Workup

  1. customin 2 h
  2. customthe reaction was quenched with water (H2O, 5 mL)
  3. extractionextracted with ethyl acetate (EtOAc, 3×15 mL)
  4. washThe combined organic extracts were washed with saturated aqueous NaCl solution (10 mL)
  5. dry with materialdried over magnesium sulfate (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was then purified by flash chromatography (SiO2, 0-50% EtOAc/hexanes gradient elution)

Sources & evidence

ORD record
ord-6c936df93bd446c591e146c6d9e25082
Source dataset
uspto-grants-2015_04
Patent number
US09000161B2

Reaction notes

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