Isobutylamine → 5-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile

Participants

Reaction Steps

Aminomalononitrile p-toluenesulfonate (15.0 g, 59.2 mmol) and triethylamine (9.08 mL, 71.1 mmol) were combined in tetrahydrofuran (THF) (200 mL) and stirred for 30 minutes; the reaction became homogeneous. Trimethyl orthobutyrate (11.4 mL, 71.1 mmol) was added, and the solution was heated at reflux for three hours. An analysis by TLC indicated the presence of starting material, and additional trimethyl orthobutyrate (5.0 mL) was added. The solution was heated at reflux for another 3.5 hours and allowed to cool to room temperature. A mixture of isobutylamine (7.06 mL, 71.1 mmol) and triethylamine (9.08 mL, 71.1 mmol) was added, and the reaction was stirred overnight. The majority of the THF was removed under reduced pressure, and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous layer was extracted twice with dichloromethane. The combined organic fractions were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to provide an orange solid that was triturated with ethyl acetate and isolated by filtration to provide 8.60 g (70%) of 5-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile as a white solid.

Provenance & Evidence