Acetonitrile → 5-(2-Butoxy-5-trimethylsilylethynyl-3-pyridinyl)-3-ethyl-2-(2-methoxy-ethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

HRID 354175Notes

Reaction equation

HRID 354175 reaction equation
[CH2:1]([O:5][C:6]1[C:11]([C:12]2[NH:13][C:14](=[O:27])[C:15]3[C:16](=[C:18]([CH2:25][CH3:26])[N:19]([CH2:21][CH2:22][O:23][CH3:24])[N:20]=3)[N:17]=2)=[CH:10][C:9](I)=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].[CH3:29][Si:30]([C:33]#[CH:34])([CH3:32])[CH3:31].C(#N)C>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:5][C:6]1[C:11]([C:12]2[NH:13][C:14](=[O:27])[C:15]3[C:16](=[C:18]([CH2:25][CH3:26])[N:19]([CH2:21][CH2:22][O:23][CH3:24])[N:20]=3)[N:17]=2)=[CH:10][C:9]([C:34]#[C:33][Si:30]([CH3:32])([CH3:31])[CH3:29])=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 66111Trimethylsilylacetylene2×HCID 1354560315-(2-Butoxy-5-iodo-3-pyridinyl)-3-ethyl-2-(2-methoxyethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Product 1

HCID 1357306155-(2-Butoxy-5-trimethylsilylethynyl-3-pyridinyl)-3-ethyl-2-(2-methoxy-ethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-oneYield 92.4%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

The title compound from Example 1 (127 mg, 0.25 mmol) was suspended in triethylamine (2 mL) and trimethylsilylacetylene (38 mg, 0.39 mmol) and acetonitrile (2 mL to try and solubilise reactants). Pd(PPh3)2Cl2 (5 mg, 0.006 mmol) and cuprous iodide (1.2 mg, 0.006 mmol) were added and the reaction mixture stirred. After 1 h a further portion of trimethylsilylacetylene (19 mg, 0.19 mmol) was added and stirring continued for 2 h. The solvent was evaporated and the residue partitioned between ethyl acetate and water. The organics were washed with brine, dried (MgSO4) and concentrated to give a brown foam. Purification by flash column chromatography (gradient elution from 100% dichloromethane to 99% dichloromethane/methanol) gave the title compound as a light brown solid (108 mg).

Workup

  1. stirringstirring
  2. customThe solvent was evaporated
  3. customthe residue partitioned between ethyl acetate and water
  4. washThe organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customto give a brown foam
  8. customPurification
  9. washby flash column chromatography (gradient elution from 100% dichloromethane to 99% dichloromethane/methanol)

Sources & evidence

ORD record
ord-44af99d8e72545c6901be9b7e8d13a4e
Source dataset
uspto-grants-2004_06
Patent number
US06756373B1

Reaction notes

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