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

HRID 334199Notes

Reaction equation

HRID 334199 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[C:7]3[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=3[N:9]=[CH:10][N:11]=2)[CH:3]=[N:2]1.[CH:23]1([C:28]#[C:29][C:30]#[N:31])[CH2:27][CH2:26][CH2:25][CH2:24]1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+]>>[CH:23]1(/[C:28](/[N:1]2[CH:5]=[C:4]([C:6]3[C:7]4[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH:3]=[N:2]2)=[CH:29]/[C:30]#[N:31])[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 574776163-Cyclopentylpropiolonitrile

Product 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)acrylonitrileYield 82.6%

Procedure

To a stirred solution of 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (17, 7.260 g, 23.01 mmol) and 3-cyclopentylprop-2-ynenitrile (8, 6.140 g, 34.52 mmol, 1.5 equiv) in N,N-Dimethylformamide (DMF, 40.0 mL, 516 mmol) at room temperature was added solid potassium carbonate (K2CO3, 318 mg, 2.30 mmol, 0.1 equiv). The resulting reaction mixture was stirred at room temperature for 30 min. When LCMS showed the reaction was deemed complete, the reaction mixture was quenched with water (80 mL), extracted with EtOAc (2×150 mL). The combined organic layers were washed with water (80 mL) and brine (50 mL), dried over magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (SiO2, 0-30% EtOAc/hexane gradient elution) to give (Z)-3-cyclopentyl-3-(4-(7((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)acrylonitrile (19, 8.256 g, 10.0 g theoretical, 82.6% yield) as a colorless syrup. For 19: 1H NMR (CDCl3, 300 MHz) δ ppm 9.15 (bs, 1H), 8.96 (s, 1H), 8.56 (s, 1H), 7.51 (d, 1H, J=3.5 Hz), 6.93 (d, 1H, J=3.5 Hz), 5.75 (s, 2H), 5.29 (s, 1H), 3.62 (m, 1H), 3.60 (t, 2H, J=8.2 Hz), 2.16 (m, 2H), 1.81 (m, 4H), 1.59 (m, 2H), 0.98 (t, 2H, J=8.2 Hz), 0.00 (s, 9H); C23H30N6OSi (MW, 434.61), LCMS (EI) m/e 435.2 (M++H).

Workup

  1. customThe resulting reaction mixture
  2. customthe reaction mixture was quenched with water (80 mL)
  3. extractionextracted with EtOAc (2×150 mL)
  4. washThe combined organic layers were washed with water (80 mL) and brine (50 mL)
  5. dry with materialdried over magnesium sulfate (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash chromatography (SiO2, 0-30% EtOAc/hexane gradient elution)

Sources & evidence

ORD record
ord-13f1f61bc759476fb8726761a755d7eb
Source dataset
uspto-grants-2014_11
Patent number
US08883806B2

Reaction notes

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