Dimethylformamide → 1-Methyl-1H-indazole-5-carboxaldehyde

HRID 456053Notes

Reaction equation

HRID 456053 reaction equation
[Li]CCCC.C([Mg]Br)C.Br[C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH3:20])[N:15]=[CH:14]2.CN([CH:24]=[O:25])C>C1(C)C=CC=CC=1.C1COCC1>[CH3:20][N:16]1[C:17]2[C:13](=[CH:12][C:11]([CH:24]=[O:25])=[CH:19][CH:18]=2)[CH:14]=[N:15]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 225587255-Bromo-1-methyl-1H-indazoleHCID 178418339ButyllithiumHCID 178418443HCID 178418443, compound

Product 1

HCID 378185941-Methyl-1H-indazole-5-carboxaldehydeYield 80.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

A suspension of n-BuLi (7.33 mL, 11.73 mmol) and ethylmagnesium bromide (5.76 mL, 5.76 mmol) in 30 mL toluene was stirred at −30° C. for 30 min, then 5-bromo-1-methyl-1H-indazole (2.25 g, 10.66 mmol) in 5 mL THF was added. After stirring at −10° C. for 1 hour, anhydrous DMF (4.95 mL, 64.0 mmol) was added at −10° C. The reaction was allowed to warm to room temperature and stirred for 2 hours. The reaction was quenched with 1N HCl and concentrated in vacuo. The residue was diluted with water, extracted with DCM twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (hexane:EtOAc=10:1) to give the title compound as a white solid (1.37 g, 76%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 10.02 (s, 1H), 8.41 (d, 1H), 8.31 (d, 1H), 7.86 (dd, 1H), 7.78 (d, 1H), 4.09 (s, 3H). LCMS (method A): [MH]+=161, tR=4.00 min.

Workup

  1. stirringAfter stirring at −10° C. for 1 hour
  2. temperatureto warm to room temperature
  3. stirringstirred for 2 hours
  4. customThe reaction was quenched with 1N HCl
  5. concentrationconcentrated in vacuo
  6. additionThe residue was diluted with water
  7. extractionextracted with DCM twice
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography (hexane:EtOAc=10:1)

Sources & evidence

ORD record
ord-0784e2a63be9412981142960a5a6b351
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

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