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

HRID 1594391Notes

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>C(O)(=O)C>[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

Conditions

Temperature: 105 °C

Procedure

To 2-tert-butyl-5-cyclobutyl-2H-pyrazol-3-ylamine (5.0 g, 25.9 mmol) in acetic acid (25 mL) was added methyl acetoacetate (5.5 mL, 51.8 mmol), and the reaction was heated to 105° C. After 19 hr, the reaction mixture was cooled to room temperature, concentrated to a viscous oil, and then taken up in EtOAc. The reaction mixture was quenched by the slow addition of an aqueous solution of NaHCO3. The layers were separated and the organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of this material was accomplished by trituration with hexanes to give, after two crops, the title compound (0.7 g, 52% yield) as a colorless solid. 400 MHz 1H NMR (CD3OD) d 6.09 (s, 1H), 3.83 (dddd, J=8.3, 8.3, 8.3, 8.3 Hz, 1H), 2.50-2.27 (m, 7H), 2.08-2.01 (m, 1H), 1.99-1.85 (m, 1H), 1.71 (s, 9H). LRMS m/z (APCI+) 260 (M+1).

Workup

temperaturethe reaction mixture was cooled to room temperature
concentrationconcentrated to a viscous oil
customThe reaction mixture was quenched by the slow addition of an aqueous solution of NaHCO3
customThe layers were separated
dry with materialthe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification of this material
customto give

Sources & evidence

ORD record: ord-9b0e448e0fe2414aac46b379b30d7ded
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07300944B2

Reaction notes

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