1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-(3-nitrophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

HRID 1817594

Reaction equation

HRID 1817594 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.C1CCN2C(=NCCC2)CC1.[N+:34]([C:37]1[CH:38]=[C:39](/[CH:43]=[CH:44]\[C:45]#[N:46])[CH:40]=[CH:41][CH:42]=1)([O-:36])=[O:35]>C(#N)C>[N+:34]([C:37]1[CH:38]=[C:39]([CH:43]([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)[CH2:44][C:45]#[N:46])[CH:40]=[CH:41][CH:42]=1)([O-:36])=[O:35]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidineHCID 66597567(2Z)-3-(3-nitrophenyl)acrylonitrile

Product 1

HCID 574806523-(3-nitrophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
67 °C

Procedure

To 4-(1H-pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine (0.500 g, 0.00158 mol) in 8.0 mL of dry ACN was added DBU (0.24 mL, 0.0016 mol) followed by addition of (2Z)-3-(3-nitrophenyl)acrylonitrile (0.36 g, 0.0021 mol) in 2.0 mL of ACN. The reaction mixture was heated at 67° C. for 18 hours. This was cooled to room temperature, and the mixture was partitioned between diluted hydrochloric acid and ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, and concentrated. The crude product was purified by flash chromatography on silica gel using ethyl acetate-hexanes 6:4, to give 3-(3-nitrophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile as a dark orange oil, (688 mg, 88.65%). LCMS (M+1)+: 490

Workup

  1. temperatureThis was cooled to room temperature
  2. customthe mixture was partitioned between diluted hydrochloric acid and ethyl acetate
  3. washThe organic layer was washed with saturated sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-b2ec10d604dc4889aeb86aebcc0e9987
Source dataset
uspto-grants-2009_10
Patent number
US07598257B2

Linked notes

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