Ethyl Acetate → 4-Chloro-2-(2-chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine

HRID 626676Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F: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.C(OCC)(=O)C.C(=O)([O-])O.[Na+].P(Cl)(Cl)([Cl:32])=O>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:32][C:13]1[C:12]2=[CH:18][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[CH:16]=[CH:15][N:14]=1

Participants

Conditions

Temperature: 85 °C

Procedure

2-(2-Chloro-6-fluorophenyl)-2H-pyrazolo[4,3-c]pyridine 5-oxide (2.13 g, 8.1 mmol) was added to a solution of tetrabutylammonium chloride (2.24 g, 8.1 mmol) in phosphorous oxychloride (16 mL) and the reaction mixture was heated at 85° C. for 5 hours. The reaction mixture was cooled to room temperature and poured into a mixture of ethyl acetate and sodium hydrogen carbonate (sat. aq.). The organic phase was separated, 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 (20% ethyl acetate in cyclohexane) to afford the title compound as a white solid (606 mg, 27% yield). 1H NMR (400 MHz, CDCl3): δ 8.36 (s, 1H), 8.12 (d, J=6.3 Hz, 1H), 7.57 (d, J=6.5 Hz, 1H), 7.55-7.50 (m, 1H), 7.45 (d, J=8.3 Hz, 1H), 7.27 (m, 1H). LCMS (Method D): RT=3.29 min, m/z: 282 [M+H+].

Workup

temperatureThe reaction mixture was cooled to room temperature
customThe organic phase was separated
washwashed 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 (20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-cb32466da680419d8593dbca86f1ab14
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309240B2

Reaction notes

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