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

HRID 626685Notes

Reaction equation

HRID 626685 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[CH:22]=[C:16]2[CH:17]=[N+:18]([O-])[CH:19]=[CH:20][C:15]2=[N:14]1.P(Cl)(Cl)([Cl:25])=O>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:25][C:17]1[C:16]2=[CH:22][N:13]([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:5][C:4]=3[Cl:12])[N:14]=[C:15]2[CH:20]=[CH:19][N:18]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 696715112-(2,6-Dichloro-4-methanesulfonylphenyl)-2H-pyrazolo[4,3-c]pyridine-5-oxide

Product 1

HCID 866970454-Chloro-2-(2,6-dichloro-4-methanesulfonylphenyl)-2H-pyrazolo[4,3-c]pyridineYield 35%

Reagents, catalysts & solvents 1

HCID 70681Tetrabutylammonium ChlorideCatalyst

Conditions

Temperature
85 °C

Procedure

2-(2,6-Dichloro-4-methanesulfonylphenyl)-2H-pyrazolo[4,3-c]pyridine-5-oxide (640 mg, 1.79 mmol) was added to a solution of tetrabutylammonium chloride (497 mg, 1.79 mmol) in phosphorous oxychloride (5 mL) and the reaction mixture was heated at 85° C. for 4 hours. The reaction mixture was cooled and partitioned between ethyl acetate and sodium hydrogen carbonate (sat. aq.). The organic phase was washed with sodium hydrogen carbonate (sat. aq.) and brine, dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The residue was purified by silica gel flash chromatography (40% ethyl acetate in cyclohexane) to afford the title compound as a white solid (238 mg, 35% yield). 1H NMR (300 MHz, DMSO-d6): δ 9.35 (d, J=1.0 Hz, 1H), 8.36 (s, 2H), 8.14 (d, J=6.3 Hz, 1H), 7.76 (dd, J=6.3, 1.0 Hz, 1H), 3.49 (s, 3H). LCMS (Method D): RT=3.19 min, m/z: 376 [M+H+].

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between ethyl acetate and sodium hydrogen carbonate (sat. aq.)
  3. washThe organic phase was washed with sodium hydrogen carbonate (sat. aq.) and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (40% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-42c2c3179e4e4ab680ffab8946751c22
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

Loading…