Methylhydrazine → 5-Amino-3-cyclohexyl-1-methyl-1H-pyrazole-4-carbonitrile

Participants

Reaction Steps

To a solution of 17.2 g (260 mmol) of malononitrile in 260 mL of tetrahydrofuran was added slowly to 20.8 g (60% dispersion in mineral oil; 520 mmol) of sodium hydride at 0° C., then, to this mixture was added by dripping 35 mL (260 mmol) of cyclohexanecarbonyl chloride at the same temperature and the mixture was stirred for 1.5 hours at room temperature. Then, 30 mL (312 mmol) of dimethyl sulfate was added to the reaction mixture and the mixture was refluxed for 3 hours. Then, 17.4 mL (125 mmol) of triethylamine and 13.8 mL (260 mmol) of methylhydrazine were added to the reaction mixture under ice cooling and the mixture was refluxed for 1 hour. After the mixture was cooled to the room temperature, the solvent was removed under reduce pressure. Water was added to the residue and the mixture was extracted with ethyl acetate and the organic layer was washed with water, and saturated saline solution, then, dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1 to 20/1). The obtained crude crystalline was further purified by recrystallization (hexane-ethyl acetate) to give 20.7 g (39%) of the title compound. The filtrate was further purified by silica gel column chromatography (eluent: hexane/ethyl acetate=2: 1) to give 11.3 g (21%) of the title compound.

Provenance & Evidence