4-Chloro-N-methylbenzenamine → HCID 90289979, compound

Participants

Reaction Conditions

Reaction Steps

Triphosgene (593 mg, 2.0 mmol) was dissolved in 13 mL of methylene chloride and cooled to 0° C. To it was added a solution of tert-butyl 2-(3-bromo-5-fluorobenzyl)hydrazinecarboxylate (1.6 g, 5 mmol) and N,N-diisopropylethylamine (1.3 mL, 7.5 mmol) in 13 mL of methylene chloride. The reaction mixture was allowed to stir at 0° C. for 20 min, and to it was added a solution of 4-chloro-N-methylaniline (726 μL, 6 mmol) in 4 mL of methylene chloride. The resulting mixture was allowed to stir at ambient temperature for 3 days. It was diluted with methylene chloride and washed with 1N HCl, half saturated NaHCO3 and half brine, then dried over MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography eluting with ethyl acetate and hexanes to afford 359 mg of tert-butyl 2-(3-bromo-5-fluorobenzyl)-2-((4-chlorophenyl)(methyl)carbamoyl)hydrazinecarboxylate (0.74 mmol). It was then dissolved in 2 mL of methanol, and to it was added 4N HCl in 1,4-dioxane (0.9 mL, 3.7 mmol). The mixture was stirred at ambient temperature overnight. The solvent was removed to afford 1-(3-bromo-5-fluorobenzyl)-N-(4-chlorophenyl)-N-methylhydrazinecarboxamide hydrochloride. MS (m/z): 387.9 [M+H]+; HPLC retention time 3.88 min (5-99% acetonitrile:water with 0.05% formic acid).

Provenance & Evidence