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

HRID 1594030Notes

Reaction equation

HRID 1594030 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:15](OC)(=[O:20])[CH2:16][C:17]([CH3:19])=O>CC(O)=O>[C:1]([N:5]1[C:9]2[NH:10][C:15](=[O:20])[CH:16]=[C:17]([CH3:19])[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 7757Methyl acetoacetateHCID 529880121-tert-butyl-3-Cyclobutyl-1H-pyrazol-5-amine

Product 1

HCID 1361404991-tert-Butyl-3-cyclobutyl-4-methyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-oneYield 52%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
105 °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 (10 mL) was added methyl acetoacetate (1.1 mL, 10.4 mmol). The reaction was then heated to 105° C. for 24 hr, at which time the reaction was cooled to room temperature, concentrated under reduced pressure to remove AcOH, diluted with EtOAc, and quenched with a saturated aqueous solution of NaHCO3. The organic layer was dried over MgSO4, filtered through a frilted funnel, and concentrated under reduced pressure. Purification of the resulting material was accomplished by trituration with hexanes. The product was collected and dried under reduced pressure to give the title compound (0.7 g, 52% yield) as a tan solid. LRMS m/z (APCl) 259.3 (M+1); 500 MHz 1H NMR (CD3OD) δ 6.09 (1, 1H), 3.83 (dddd, J=8.7, 8.7, 8.7, 8.7 Hz, 1H), 2.49-2.28 (m, 4H), 2.42 (d, J=0.8 Hz, 3H), 2.11-2.01 (m, 1H), 1.94-1.86 (m, 1H), 1.71 (s, 9H).

Workup

  1. temperaturewas cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customto remove AcOH
  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 frilted funnel
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the resulting material
  10. customThe product was collected
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-8d111198326545a7a270e4d53520dc78
Source dataset
uspto-grants-2007_11
Patent number
US07300943B2

Reaction notes

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