Sodium Carbonate → 4-Chloro-2-(2-chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

HRID 626795Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[N:9]1[CH:19]=[C:12]2[CH:13]=[N+:14]([O-])[CH:15]=[C:16]([F:17])[C:11]2=[N:10]1.P(Cl)(Cl)([Cl:22])=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCCl>[Cl:22][C:13]1[C:12]2=[CH:19][N:9]([C:3]3[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[N:10]=[C:11]2[C:16]([F:17])=[CH:15][N:14]=1

Participants

Conditions

Temperature: 70 °C

Procedure

2-(2-Chloro-6-fluorophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5 oxide (7.2 g, 25.6 mmol) was suspended in DCE (130 mL) under an atmosphere of nitrogen and phosphorus oxychloride (7.2 mL, 77.0 mmol) was added. The reaction mixture was heated at 70° C. for 5 hours and then allowed to cool to room temperature. The resultant mixture was poured cautiously onto saturated aqueous sodium carbonate solution, with stirring, and the layers were separated. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane) to afford the title compound as a white solid (3.08 g, 40% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.54 (d, J=2.5 Hz, 1H), 8.22 (d, J=3.4 Hz, 1H), 7.86-7.78 (m, 1H), 7.76-7.66 (m, 2H).

Workup

temperatureto cool to room temperature
customthe layers were separated
washThe organic layer was washed with brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-6110e9b1c89c4d0bb2d7540204893a0c
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309240B2

Reaction notes

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