Ethyl 3-oxo-2-phenylpropanoate → 1-tert-Butyl-3-cyclobutyl-5-phenyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-one

HRID 1594031Notes

Reaction equation

HRID 1594031 reaction equation
[C:1]([N:5]1[C:9]([NH2:10])=[CH:8][C:7]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].C([O:17][C:18](=O)[CH:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:20]=O)C>CC(O)=O>[C:1]([N:5]1[C:9]2[NH:10][C:18](=[O:17])[C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:20][C:8]=2[C:7]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[N:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 562729Ethyl 3-oxo-2-phenylpropanoateHCID 529880121-tert-butyl-3-Cyclobutyl-1H-pyrazol-5-amine

Product 1

HCID 1363386371-tert-Butyl-3-cyclobutyl-5-phenyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-oneYield 9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

To a stirring solution of crude 2-tert-butyl-5-cyclobutyl-2H-pyrazol-3-ylamine (1.0 g, 5.2 mmol) in AcOH (5 mL) was added 3-oxo-2-phenyl-propionic acid ethyl ester (1.0 g, 5.2 mmol). The reaction was then heated to 110° C. for 18 hr, at which time the reaction was cooled to room temperature, concentrated under reduced pressure to remove HOAc, diluted with EtOAc, and quenched with a saturated aqueous solution of NaHCO3. The organic layer was dried over MgSO4, filtered through a fritted funnel, and concentrated under reduced pressure. Purification of the resulting material was accomplished by flash chromatography with a Biotage® 35L column (A Dynax Corp., Charlottesville, Va.), eluting with a gradient of 5%, 10%, 20% EtOAc/hexanes. The product was collected and concentrated under reduced pressure to give the title compound (15 mg, 9% yield). LRMS m/z (APCl) 322 (M+1).

Workup

  1. temperaturewas cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customto remove HOAc
  4. additiondiluted with EtOAc
  5. customquenched with a saturated aqueous solution of NaHCO3
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered through a fritted funnel
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the resulting material
  10. wash), eluting with a gradient of 5%, 10%, 20% EtOAc/hexanes
  11. customThe product was collected
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ed9a8f3b42ba49bdbc3fc4c83f483ba6
Source dataset
uspto-grants-2007_11
Patent number
US07300943B2

Reaction notes

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