Methyl 2,2-dimethoxypropionate → 1-tert-Butyl-3-cyclobutyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-one

HRID 1594034Notes

Reaction equation

HRID 1594034 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].CO[C:17](OC)([CH3:22])[C:18](OC)=[O:19]>CC(O)=O>[C:1]([N:5]1[C:9]2[NH:10][C:18](=[O:19])[CH:17]=[CH:22][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 82339Methyl 2,2-dimethoxypropionateHCID 529880121-tert-butyl-3-Cyclobutyl-1H-pyrazol-5-amine

Product 1

HCID 1361405021-tert-Butyl-3-cyclobutyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-oneYield 32%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

To 2-tert-butyl-5-cyclobutyl-2H-pyrazol-3-ylamine (5.0 g, 25.9 mmol) in AcOH (25 mL) was added methyl dimethoxypropionate (7.4 mL, 51.8 mmol), and then the reaction was heated to 110° C. After 24 hr, the reaction mixture was cooled to room temperature, and concentrated to a viscous oil that was treated with EtOAc. The organic layer was washed with aqueous NaHCO3 dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of this material was accomplished by MPLC using a 45L Biotage® column eluting with 20% EtOAc/hexanes. The product-containing fractions were collected and concentrated under reduced pressure, and the resulting solid was washed with hexanes and dried to afford the title compound (2.0 g, 32% yield) as a colorless solid. Rf=0.33 (10% MeOH/CH2Cl2); 500 MHz 1H NMR (CDCl3) d 7.72 (d, J=9.1 Hz, 1H), 6.26 (d, J=9.1 Hz, 1H), 3.68 (dddd, J=8.7, 8.7, 8.7, 8.7 Hz, 1H), 2.46-2.32 (m, 4H), 2.14-1.89 (m, 2H), 1.71 (s, 9H); LRMS m/z (APCl+) 246 (M+1).

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. concentrationconcentrated to a viscous oil that
  3. additionwas treated with EtOAc
  4. washThe organic layer was washed with aqueous NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification of this material
  9. washeluting with 20% EtOAc/hexanes
  10. customThe product-containing fractions were collected
  11. concentrationconcentrated under reduced pressure
  12. washthe resulting solid was washed with hexanes
  13. customdried

Sources & evidence

ORD record
ord-67aa499e1b93441080dafe2ef9050f32
Source dataset
uspto-grants-2007_11
Patent number
US07300943B2

Reaction notes

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