Phosphorus oxychloride → 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

HRID 626659

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:18]=[C:12]2[CH:13]=[N+:14]([O-])[CH:15]=[CH:16][C:11]2=[N:10]1.P(Cl)(Cl)([Cl:21])=O.C(=O)([O-])O.[Na+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[Cl:21][C:13]1[C:12]2=[CH:18][N:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])[N:10]=[C:11]2[CH:16]=[CH:15][N:14]=1

Participants

Conditions

Temperature: 80 °C

Procedure

2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine 5-oxide (1.12 g, 4 mmol) was slowly added to phosphorous oxychloride (8 mL). Tetrabutylammonium chloride (1.11 g, 4 mmol) was then added. The reaction mixture was heated at 80° C. for 5 hours and then cooled to room temperature. The reaction was poured into a mixture of ethyl acetate and sodium hydrogen carbonate (sat. aq.) and the layers were partitioned. The organic layer was washed with sodium hydrogen carbonate (sat. aq.) and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane) to afford the title compound as a white solid (590 mg, 49% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.33 (d, J=1.0 Hz, 1H), 8.11 (d, J=6.0 Hz, 1H), 7.83 (d, J=1.3 Hz, 1H), 7.82-7.81 (m, 1H), 7.75-7.71 (m, 1H). LCMS (Method D): RT=3.42 min, m/z: 298 [M+H+].

Workup

temperaturecooled to room temperature
customthe layers were partitioned
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 resultant residue was purified by silica gel flash chromatography (20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-4dd650f0ed7046cb95d4f42a57c97827
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309240B2

Linked notes

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