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 2187122Notes

Reaction equation

HRID 2187122 reaction equation
[C:1]([C:4]1[C:8]([NH:9][C:10](=O)[C:11]2[CH:16]=[C:15](S(N3CCN(CC)CC3)(=O)=O)[CH:14]=[N:13][C:12]=2[O:28][CH2:29][CH3:30])=[C:7]([CH2:32][CH3:33])[N:6]([CH2:34][CH2:35][O:36][CH3:37])[N:5]=1)(=[O:3])[NH2:2].[CH3:38][Si:39]([C:42]#[CH:43])([CH3:41])[CH3:40].[C:44](#N)[CH3:45]>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>[CH2:29]([O:28][C:12]1[C:11]([C:10]2[NH:2][C:1](=[O:3])[C:4]3[C:8](=[C:7]([CH2:32][CH3:33])[N:6]([CH2:34][CH2:35][O:36][CH3:37])[N:5]=3)[N:9]=2)=[CH:16][C:15]([C:43]#[C:42][Si:39]([CH3:41])([CH3:40])[CH3:38])=[CH:14][N:13]=1)[CH2:30][CH2:44][CH3:45]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 66111Trimethylsilylacetylene2×HCID 11478208N-[3-Carbamoyl-5-ethyl-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-ethoxy-5-(4-ethylpiperazine-1-sulfonyl)pyridine-3-carboxamide

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-one

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

The title compound from Example 1 of PCT application IB00/1430 (127 mg, 0.25 mmol) was suspended in triethylamine (2 mL) and trimethylsilylacetylene (38 mg, 0.39 mmol) and acetonitrile (2 mL). 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-d6e74d99c3534acb8b587274602d09ce
Source dataset
uspto-grants-2002_06
Patent number
US06407259B1

Reaction notes

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