Phosphorus oxychloride → 4-Chloro-2-(2,6-dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine

HRID 626766Notes

Reaction equation

HRID 626766 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([Cl:11])[C:3]=1[N:12]1[CH:22]=[C:15]2[CH:16]=[N+:17]([O-])[CH:18]=[C:19]([F:20])[C:14]2=[N:13]1.P(Cl)(Cl)([Cl:25])=O>ClCCCl>[Cl:25][C:16]1[C:15]2=[CH:22][N:12]([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][C:4]=3[Cl:11])[N:13]=[C:14]2[C:19]([F:20])=[CH:18][N:17]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 696716022-(2,6-Dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5-oxide

Product 1

HCID 866970684-Chloro-2-(2,6-dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridineYield 40.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

2-(2,6-Dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5-oxide (4.20 g, 12.24 mmol) was suspended in DCE (60 mL), under an atmosphere of nitrogen and phosphorus oxychloride (3.61 mL, 39.2 mmol) was added. The reaction mixture was heated at 70° C. for 95 minutes. The resultant mixture was cooled to room temperature and was carefully quenched by the addition of 10% aqueous sodium carbonate solution. The layers were separated and the aqueous layer was extracted with DCM (×4). The combined organic layers were filtered to remove insoluble solids, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane) to afford the title compound as a pale yellow solid (1.78 g, 40% yield). 1H NMR (300 MHz, CDCl3): δ 8.43 (s, 2H), 8.37 (d, J=2.2 Hz, 1H), 8.03 (d, J=3.0 Hz, 1H).

Workup

  1. customwas carefully quenched by the addition of 10% aqueous sodium carbonate solution
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with DCM (×4)
  4. filtrationThe combined organic layers were filtered
  5. customto remove insoluble solids
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-f61855f85da547ceacd134b6048fb4a0
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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