Isobutylamine → 5-Amino-1-isobutyl-1H-imidazole-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a suspension of aminomalononitrile p-toluenesulfonate (1 g, 4.0 mmol, 1 equiv) in THF (30 mL) at 25° C. was added NEt3 (0.65 mL, 4.8 mmol, 1.2 equiv) in one portion. The mixture was stirred for 30 min to afford a homogeneous solution. To this solution was added triethyl orthoformate (0.80 mL, 4.8 mmol, 1.2 equiv) and the solution was heated at reflux for 3 h. TLC indicated the presence of starting material and additional triethyl orthoformate (0.4 mL, 2.4 mmol, 0.6 equiv) was added. The solution was heated at reflux for another 2 h then cooled to 25° C. NEt3 (0.65 mL, 4.8 mmol, 1.2 equiv) and isobutylamine (350 mg, 4.8 mmol, 1.2 equiv) were added sequentially and the reaction was stirred at 25° C. for 15 h. The reaction was concentrated in vacuo and the crude residue was redissolved in CH2Cl2 (100 mL) and washed with saturated Na2CO3 solution (25 mL) The aqueous layer was extracted with CH2Cl2 (3×20 mL). The combined organic fractions were washed with saturated aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Purification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient) afforded the title compound (426 mg, 65%) as a light yellow solid: 1H NMR (CDCl3, 600 Hz) δ 0.96 (d, J=6.6 Hz, 6H), 2.01-2.07 (m, 1H), 3.57 (d, J=7.8 Hz, 2H), 3.94 (br s, 2H), 7.05 (s, 1H); 13C NMR (CDCl3, 150 Hz) δ 19.8, 28.9, 51.6, 115.7, 116.5, 133.5, 144.8; MS (ESI+): calcd C8H13N4 [M+H]+ 165.1. found 165.1.

Provenance & Evidence