3-Bromopropionitrile → 3-[1-(4-Methoxy-phenyl)-7-oxo-3-trifluoromethyl-1,4,5,7-tetrahydro-pyrazolo[3,4-c]pyridin-6-yl]-propionitrile

HRID 720440Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[C:14](=[O:18])[NH:15][CH2:16][CH2:17][C:12]=3[C:11]([C:19]([F:22])([F:21])[F:20])=[N:10]2)=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:26][CH2:27][C:28]#[N:29]>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]3[C:14](=[O:18])[N:15]([CH2:26][CH2:27][C:28]#[N:29])[CH2:16][CH2:17][C:12]=3[C:11]([C:19]([F:22])([F:20])[F:21])=[N:10]2)=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1-(4-Methoxy-phenyl)-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one (1.00 g, 3.213 mmol) was dissolved in N,N-dimethylformamide (75 mL) and cooled to 0° C. Sodium hydride (60%, 0.321 g, 8.032 mmol) was added followed by 3-bromopropionitrile (0.533 mL, 6.425 mmol). The reaction was stirred at rt overnight, quenched with 1N hydrochloric acid (250 mL), extracted with ethyl acetate (3×200 mL), washed with water (2×200 mL), washed with brine (1×200 mL), dried over MgSO4, concentrated, and purified by flash chromatography using 0–100% ethyl acetate/hexanes gradient as the eluent to afford the title compound (1.03 g, 88%): Mass Spec 382.4(M+H+H2O)+.

Workup

customquenched with 1N hydrochloric acid (250 mL)
extractionextracted with ethyl acetate (3×200 mL)
washwashed with water (2×200 mL)
washwashed with brine (1×200 mL)
dry with materialdried over MgSO4
concentrationconcentrated
custompurified by flash chromatography

Sources & evidence

ORD record: ord-3fff5778301640eda6de26d15ef5130e
Source dataset: uspto-grants-2006_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07135469B2

Reaction notes

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