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

Participants

Reaction Conditions

Reaction Steps

Aminomalononitrile p-toluenesulfonate (744.65 g, 2.94 mol), triethylamine (297.5 g, 2.94 mol), and trimethyl orthobutyrate (436 g, 2.94 mol) were combined in toluene (7.45 L) and the solution was heated at 60° C. for 2.5 hours. Additional trimethyl orthobutyrate (21 g) was added, and the reaction was allowed to cool over a period of 30 minutes, and triethylamine (297.5 g, 2.94 mol) was added. The solution was further cooled to about 3° C. over 30 minutes, and isobutylamine (215.03 g, 2.94 mol) was added over a period of 90 minutes. During the addition, the reaction temperature rose to 10° C. The reaction was warmed to room temperature slowly and stirred overnight. Deionized water (7.35 L) and sodium carbonate (735 g) were added over a period of 15 minutes while maintaining the temperature of the mixture at 20° C. with the addition of ice. The mixture was stirred for 15 minutes, and then the precipitate was isolated by filtration, washed sequentially with toluene (300 mL) and water (3 L), air-dried, and further dried under vacuum at 70° C. for 24 hours to provide 394.4 g (65%) of 5-amino-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile as a beige solid, mp 134.5-136.5° C.

Provenance & Evidence