Dimethylformamide → 1H-Pyrazolo[3,4-C]pyridine-5-carboxaldehyde

HRID 899413Notes

Reaction equation

HRID 899413 reaction equation
[Li]C(C)(C)C.Br[C:7]1[CH:8]=[C:9]2[CH:15]=[N:14][NH:13][C:10]2=[CH:11][N:12]=1.CN([CH:19]=[O:20])C>C1COCC1>[NH:13]1[C:10]2=[CH:11][N:12]=[C:7]([CH:19]=[O:20])[CH:8]=[C:9]2[CH:15]=[N:14]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 457897785-Bromo-1H-pyrazolo[3,4-c]pyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 596944711H-Pyrazolo[3,4-C]pyridine-5-carboxaldehydeYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

t-BuLi (27 mL, 1.7 M in pentane) was added to 100 mL of THF at −78° C. 5-bromo-1H-pyrazolo[3,4-c]pyridine (3.0 g, 15 imol) was added dropwise to the solution in 50 ml of THF via addition funnel. The resulting mixture was stirred for 1 h, at which point DMF (6.0 mL, 76 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred 2 h. The reaction was then carefully quenched with aq. NH4Cl and diluted with EtOAc. The resulting biphasic mixture was partitioned in a separatory funnel. The aqueous portion was extracted three tines with EtOAc, and the combined organic extracts were washed with brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (100% CH2Cl2 to 7.5% MeOH/CH2Cl2), afforded the desired 1H-pyrazolo[3,4-c]pyridine-5-carbaldehyde (1.1 g, 50% yield) as a white solid. H1 NMR (MeOD, 400 MHz) keto tautomer: 10.17 (s, 1H), 9.19 (s, 1H), 8.56 (s, 1H), 8.46 (s, 1H); enol tautomer: 9.00 (s, 1H), 8.25 (s, 1H), 8.05 (s, 2H), 5.73 (s, 1H). MS (API-ES) m/z (%): 141 (100%, M++1).

Workup

  1. additionwas added dropwise
  2. customThe reaction was then carefully quenched with aq. NH4Cl
  3. additiondiluted with EtOAc
  4. customThe resulting biphasic mixture was partitioned in a separatory funnel
  5. extractionThe aqueous portion was extracted three tines with EtOAc
  6. washthe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-f49bdc52656d43ac9d4c8b7ad1751781
Source dataset
uspto-grants-2008_04
Patent number
US07354944B2

Reaction notes

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