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

HRID 1796546Notes

Reaction equation

HRID 1796546 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 aqueous ammonium hydroxide. The resulting slurry was extracted with dichloromethane. 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): δ 10.07 (s, 1H), 8.49 (d, 1 H), 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. 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-5b73ab6f701342d6941bc5d6516e314b
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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