Dimethylformamide → 5-chloro-1H-indazole-7-carbaldehyde

HRID 913828Notes

Reaction equation

HRID 913828 reaction equation
Br[C:2]1[CH:3]=[C:4]([Cl:11])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.[H-].[Na+].C([Li])(C)(C)C.CCCCC.CN(C)[CH:26]=[O:27].[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[Cl:11][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([CH:26]=[O:27])[CH:3]=1)[NH:9][N:8]=[CH:7]2

Participants

9

Reactant 6

HCID 6228DimethylformamideHCID 8003PentaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 269676217-Bromo-5-chloro-1H-indazoleHCID 178418306HCID 178418306, compound

Product 1

HCID 575461125-chloro-1H-indazole-7-carbaldehyde

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

7-Bromo-5-chloro-1H-indazole (0.44 g, 1.90 mmol) and sodium hydride were combined in tetrahydrofuran (5 mL) at 0° C. After 15 min, cooling was removed and the mixture stirred at room temperature for 20 min. The stirred mixture was cooled to −78° C. and treated with a solution of tert-butyllithium in pentane (1.7 M, 2.4 mL, 3.99 mmol) over several minutes. The mixture was allowed to gradually warm to −20° C. over 1 h, re-cooled to −78° C. and treated with dimethylformamide (220 μL, 2.85 mmol). The reaction was warmed to 0° C. over several hours, then treated with saturated ammonium chloride. The reaction was diluted with ethyl acetate. The layers were separated. The organic layer was washed with brine (2×), dried over sodium sulfate, filtered and concentrated to afford 0.3 g (87%) as a white powder. LC/MS (HPLC method 1): tR=1.88 min, 181.02(MH)+.

Workup

  1. temperaturecooling
  2. customwas removed
  3. temperatureThe stirred mixture was cooled to −78° C.
  4. temperatureto gradually warm to −20° C. over 1 h
  5. temperaturere-cooled to −78° C.
  6. temperatureThe reaction was warmed to 0° C. over several hours
  7. customThe layers were separated
  8. washThe organic layer was washed with brine (2×)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford 0.3 g (87%) as a white powder

Sources & evidence

ORD record
ord-6e5e2a4ad4a94b378d3560e456caa8ce
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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