Methyl 4,4,4-trifluoro-3-oxobutanoate → 1-tert-Butyl-3-cyclobutyl-4-trifluoromethyl-1,7-dihydro-pyrazolo[3,4-b]pyridin-6-one

HRID 1594032Notes

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:16][C:17](=O)[CH2:18][C:19](=O)[C:20]([F:23])([F:22])[F:21]>CC(O)=O>[C:1]([N:5]1[C:9]2[NH:10][C:17](=[O:16])[CH:18]=[C:19]([C:20]([F:23])([F:22])[F:21])[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: 110 °C

Procedure

To a stirring solution of crude 2-tert-butyl-5-cyclobutyl-2H-pyrazol-3-ylamine (2.0 g, 10.4 mmol) in AcOH (10 mL) was added 4,4,4-trifluoro-3-oxo-butyric acid methyl ester (3.5 g, 20.7 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, 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 to give the title compound (3.2 g, quantitative yield). This material was used without further purification. LRMS m/z (APCl) 314 (M+1); 500 MHz 1H NMR (CDCl3) δ 6.66 (s, 1H), 3.78 (dddd, J=8.3, 8.3, 8.3, 8.3 Hz, 1H), 2.49-2.39 (m, 2H), 2.34-2.26 (m, 2H), 2.06-1.85 (m, 2H), 1.75 (s, 9H).

Workup

temperaturewas cooled to room temperature
concentrationconcentrated under reduced pressure
additiondiluted with EtOAc
customquenched with a saturated aqueous solution of NaHCO3
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered through a fritted funnel
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-0e0dc2a006ee4754a6b6fec1be9dff6d
Source dataset: uspto-grants-2007_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07300943B2

Reaction notes

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