Dimethylformamide → 5-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde

HRID 896784Notes

Reaction equation

HRID 896784 reaction equation
P(Cl)(Cl)(Cl)=O.[Cl:6][C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:15]=[C:9]2[CH:8]=1.[OH-].[NH4+].CN(C)[CH:27]=[O:28]>>[Cl:6][C:7]1[CH:12]=[CH:11][N:10]2[N:13]=[C:14]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)[C:15]([CH:27]=[O:28])=[C:9]2[CH:8]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 221748455-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine

Product 1

HCID 219486825-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde

Procedure

Phosphorous oxychloride (0.6 mL, 6.4 mmol) was added to N,N-dimethylformamide (10 mL) and the resulting mixture stirred at room temperature for 10 minutes. 5-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine (1.0 g, 4.1 mmol) was added and the reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into ice-water and neutralized to pH 7 with aquous ammonium hydroxide. The resulting slurry was extracted with dichloromethane (3×40 mL). The combined organics were washed with brine, dried (magnesium sulfate), filtered and concentrated to give, after recrystallization from acetonitrile, 5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde (0.95 g, 85%) as a white solid. 1H-NMR (CDCl3): δ10.07 (s, 1H), 8.49 (d, 1H), 8.44 (d, 1H), 7.78 (q, 2H), 7.22 (t, 2H), 7.07 (dd, 1H); MS m/z 275 (M+1).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 12 hours
  2. extractionThe resulting slurry was extracted with dichloromethane (3×40 mL)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give
  8. customafter recrystallization from acetonitrile, 5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde (0.95 g, 85%) as a white solid

Sources & evidence

ORD record
ord-7266bfef7a3e449d80f25b49d6a06d72
Source dataset
uspto-grants-2005_07
Patent number
US06919352B2

Reaction notes

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