Phosphorus oxybromide → 4-Bromo-2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine

HRID 626739Notes

Reaction equation

HRID 626739 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:20]=[C:12]2[CH:13]=[N+:14]([O-])[CH:15]=[C:16]([O:17][CH3:18])[C:11]2=[N:10]1.P(Br)(Br)([Br:23])=O>ClCCCl>[Br:23][C:13]1[C:12]2=[CH:20][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[C:16]([O:17][CH3:18])=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 24613Phosphorus oxybromide2×HCID 696715972-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine 5-oxide

Product 1

HCID 866970604-Bromo-2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridineYield 9.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a cooled (0° C.) solution of 2-(2,6-dichlorophenyl)-7-methoxy-2H-pyrazolo[4,3-c]pyridine 5-oxide (1.3 g, 4.2 mmol) in DCE (30 mL) under nitrogen was added phosphorous oxybromide (2.4 g, 8.4 mmol). The reaction mixture was stirred for 30 minutes, warmed to room temperature, and stirred for a further 4 hours. Further phosphorous oxybromide (1.8 g, 6.3 mmol) was added and the reaction mixture was stirred for a further 16 hours. The temperature was raised to 80° C. and stirred for 2 hours. The resultant mixture was cooled, quenched with sodium carbonate (sat. aq.) and the layers were partitioned. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (30-40% ethyl acetate in cyclohexane) to afford the title compound as a white solid (143 mg, 9% yield). LCMS (Method D): RT=3.52 min, m/z: 372 [M+H+].

Workup

  1. stirringstirred for a further 4 hours
  2. stirringthe reaction mixture was stirred for a further 16 hours
  3. temperatureThe temperature was raised to 80° C.
  4. stirringstirred for 2 hours
  5. customquenched with sodium carbonate (sat. aq.)
  6. customthe layers were partitioned
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant residue was purified by silica gel flash chromatography (30-40% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-38efb8aa47184b9e8863a239bffde7a8
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

Loading…