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

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Reaction Steps

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)).

Provenance & Evidence