Acetonitrile → methyl 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutanecarboxylate

HRID 1692914Notes

Reaction equation

HRID 1692914 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.C(#N)C.[C:26]([CH:28]=[C:29]1[CH2:32][CH:31]([C:33]([O:35][CH3:36])=[O:34])[CH2:30]1)#[N:27].N12CCCN=C1CCCCC2>>[C:26]([CH2:28][C:29]1([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)[CH2:32][CH:31]([C:33]([O:35][CH3:36])=[O:34])[CH2:30]1)#[N:27]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 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 45090084Methyl 3-(cyanomethylene)cyclobutanecarboxylate

Product 1

HCID 67017201methyl 3-(cyanomethyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]cyclobutanecarboxylate

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(1H-pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine (2.01 g, 0.00637 mol) in acetonitrile (4.0E1 mL, 0.77 mol) was added methyl 3-(cyanomethylene)cyclobutanecarboxylate (1.93 g, 0.0127 mol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.953 mL, 0.00637 mol). The resulting mixture was stirred at 50° C. overnight. After evaporation to dryness, the residue was purified on silica gel, eluting with 0 to 100% EtOAc in hexane, to give the desired Micheal addition product as a mixture of cis- and trans-isomers (2.12 g, 71.3%). LCMS calculated for C23H31N6O3Si(M+H)+: 467.2; Found: 467.4.

Workup

  1. customAfter evaporation to dryness
  2. customthe residue was purified on silica gel
  3. washeluting with 0 to 100% EtOAc in hexane
  4. customto give the desired
  5. additionMicheal addition product
  6. additionas a mixture of cis- and trans-isomers (2.12 g, 71.3%)

Sources & evidence

ORD record
ord-eb7ff4d3e40140ce8cc0e690c4f8d572
Source dataset
uspto-grants-2012_04
Patent number
US08158616B2

Reaction notes

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