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

HRID 1959618Notes

Reaction equation

HRID 1959618 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 toluene (30 mL) was stirred at −30° C. for 30 min, and then a solution of 5-bromo-1-methyl-1H-indazole (2.25 g, 10.66 mmol) in THF (5 mL) was added. After 1 h, anhydrous DMF (4.95 mL, 64.0 mmol) was added at −10° C. The reaction mixture was allowed to warm to rt and stirred for 2 h. The reaction was quenched with saturated aqueous NH4Cl solution 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) δppm 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. waitAfter 1 h
  2. temperatureto warm to rt
  3. stirringstirred for 2 h
  4. customThe reaction was quenched with saturated aqueous NH4Cl solution
  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-d48de0a53c904534b1704b0981c11952
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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