4-Toluenesulfonyl chloride → 4-chloro-3,5-dimethyl-1-tosyl-1H-indazole

Participants

Reaction Conditions

Reaction Steps

A solution of 1-(2-chloro-6-fluoro-3-methylphenyl)ethanone (10 g, 53.6 mmol) and hydrazine (5.05 mL, 161 mmol) in DMSO (50 mL) was heated at 80° C. overnight. The reaction mixture was then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to provide crude 4-chloro-3,5-dimethyl-1H-indazole as a white solid, which was used in the next step directly. MS (ESI+) m/z 180.9 (M+H)+. NaH (60% dispersion in mineral oil, 3.87 g, 97 mmol) was added portion wise to a solution of crude 4-chloro-3,5-dimethyl-1H-indazole (9.7 g, 53.7 mmol) in THF (200 mL) at −20° C. The mixture was allowed to warm to 0° C. and stir for 20 min, then TsCl (14.33 g, 75 mmol) was added. The reaction mixture was allowed to warm to rt and stir overnight. The reaction mixture was cooled to −20° C. and sat. NH4Cl aqueous solution was added to quench excess base. The resulting mixture was extracted with CH2Cl2 (2×). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was triturated with EtOAc and filtered to provide 4-chloro-3,5-dimethyl-1-tosyl-1H-indazole. 1H NMR (400 MHz, CDCl3) δ ppm 7.98 (d, J=8.34 Hz, 1 H) 7.84 (m, J=8.34 Hz, 2 H) 7.39 (d, J=8.59 Hz, 1 H) 7.25 (m, J=7.83 Hz, 2 H) 2.73 (s, 3 H) 2.46 (s, 3 H) 2.38 (s, 3 H); MS (ESI+) m/z 334.7 (M+H)+.

Provenance & Evidence