N-Methylformanilide → 4,6-difluoro-1-methyl-1H-indazole-5-carbaldehyde

HRID 1942062Notes

Reaction equation

HRID 1942062 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:12].[Li+].CC([N-]C(C)C)C.CN([CH:29]=[O:30])C1C=CC=CC=1>C1COCC1>[F:1][C:2]1[C:10]([CH:29]=[O:30])=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:12]

Participants

5

Reactant 3

HCID 66737N-MethylformanilideHCID 2724682Lithium diisopropylamideHCID 579174794,6-Difluoro-1-methyl-1H-indazole

Product 1

HCID 579173344,6-difluoro-1-methyl-1H-indazole-5-carbaldehyde

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4,6-difluoro-1-methyl-1H-indazole ((xvi), 168 mg, 1 mmol) in dry THF (1 mL) was added dropwise to a freshly prepared solution of LDA (n-BuLi 1.25 mL and diisopropylamine 0.285 mL, 2 mmol, in 10 mL THF) at −78° C. The solution was stirred at this temperature for 2 h, and then N-methylformanilide (0.247 mL, 2 mmol) was added dropwise at −70° C. After stirring 2 additional hours at −78° C. the RM was quenched with glacial acetic acid, diluted with water, and extracted twice with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4 and the solvent was removed. The residue was purified by flash chromatography to afford the title compound as a yellowish crystalline powder (tR 4.49 min (conditions 5), MH+=197, 1H-NMR in DMSO-d6: 10.2 (s, 1H); 8.42 (s, 1H); 7.61 (d, 1H); 4.04 (s, 3H)).

Workup

  1. stirringAfter stirring 2 additional hours at −78° C. the RM
  2. customwas quenched with glacial acetic acid
  3. additiondiluted with water
  4. extractionextracted twice with EtOAc
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent was removed
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-c8e197fa50b54e57a6d4892ae4d8b3f0
Source dataset
uspto-grants-2013_03
Patent number
US08389526B2

Reaction notes

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