Dimethylformamide → 6-fluoro-1H-indazole-5-carbaldehyde

HRID 69136Notes

Reaction equation

HRID 69136 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][N:6]=[CH:5]2.[H-].[Na+].CN([CH:17]=[O:18])C>C1COCC1>[F:11][C:10]1[CH:9]=[C:8]2[C:4]([CH:5]=[N:6][NH:7]2)=[CH:3][C:2]=1[CH:17]=[O:18]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 468639235-Bromo-6-fluoro-1H-indazole

Product 1

HCID 579172916-fluoro-1H-indazole-5-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

A solution of 5-bromo-6-fluoro-1H-indazole (3 g, 13.95 mmol) in THF (10 mL) was added to a suspension of NaH (3.38 g, 141 mmol) in THF (100 mL) over 10 min at 0° C. The RM was cooled to −70° C. then the s-Buli solution (1.4 M, 19 mL) was added slowly over 20 min. It was stirred at this temperature for 45 min. A solution of DMF (6.18 mL, 80 mmol) in THF (10 mL) was added over 15 min at −70° C. and the RM was then warmed up to rt over 1 h 30. The reaction was quenched with 100 mL of 1 N HCl. The RM was extracted twice with EtOAc. Then the organics were joined and washed with brine, dried over Na2SO4 and the solvent was removed. The residue was triturated for 1 h with Et2O. The precipitate formed was filtered off and identified as the desired aldehyde. The filtrate was left in the freezer over night and a second batch of the product was filtered off to afford the title compound as a light yellow solid (tR 0.7 min (conditions 2), MH+=165, 1H-NMR in DMSO-d6: 13.50 (s, 1H); 10.15 (s, 1H); 8.39 (d, 1H); 8.32 (s, 1H); 7.45 (d, 1H)).

Workup

  1. temperaturethe RM was then warmed up to rt over 1 h 30
  2. customThe reaction was quenched with 100 mL of 1 N HCl
  3. extractionThe RM was extracted twice with EtOAc
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed
  7. customThe residue was triturated for 1 h with Et2O
  8. customThe precipitate formed
  9. filtrationwas filtered off
  10. waitThe filtrate was left in the freezer over night
  11. filtrationa second batch of the product was filtered off

Sources & evidence

ORD record
ord-791dd7a128fa472780a4f13c06961939
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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