Phosphorus oxychloride → 4-Chloro-2-(2,6-dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine

HRID 626702Notes

Reaction equation

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

Participants

Conditions

Temperature: 85 °C

Procedure

2-(2,6-Dichloro-4-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine-5-oxide (1.4 g, 4.7 mmol) was slowly added to phosphorous oxychloride (10 mL). Tetrabutylammonium chloride (1.31 g, 4.7 mmol) was then added and the reaction mixture was heated at 85° C. for 45 minutes. The mixture was cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and sodium hydrogen carbonate. The organic layer was washed with sodium hydrogen carbonate (sat. aq.) and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (10-20% ethyl acetate in cyclohexane) to afford the title compound as a white solid (706 mg, 47% yield). 1H NMR (300 MHz, DMSO-d6): δ 9.28 (s, 1H), 8.11 (d, J=6.3 Hz, 1H), 7.94 (d, J=8.4 Hz, 2H), 7.72 (d, J=6.3 Hz, 1H).

Workup

temperatureThe mixture was cooled
concentrationconcentrated under reduced pressure
customThe residue was partitioned between ethyl acetate and sodium hydrogen carbonate
washThe organic layer was washed with sodium hydrogen carbonate (sat. aq.) and brine
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel flash chromatography (10-20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-a0f533aba83c461b80ee40035f9533eb
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309240B2

Reaction notes

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