Diisopropylethylamine → tert-butyl [2-methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]carbamate

Participants

Reaction Steps

tert-Butyl 2-ethanimidoylhydrazinecarboxylate (17.3 g, 99.9 mmol), 2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone (16.89 g, 83.18 mmol) and N,N-diisopropylethylamine (31.9 mL, 183 mmol) were combined in ice-cold 2-methyltetrahydrofuran (400 mL) and 1,2-dimethoxyethane (100 mL), and the reaction mixture was heated to reflux. After 2.5 hours, the reaction was cooled and washed with 50% saturated aqueous sodium chloride solution (75 mL). The aqueous layer was extracted with 2-methyltetrahydrofuran (100 mL), and the combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was dissolved in warm ethyl acetate (60 mL), allowed to cool to room temperature, then cooled to 5° C. for 30 minutes. The resulting solid was collected by filtration and washed with a small quantity of cold ethyl acetate, then washed with diethyl ether, to provide the product as a very pale yellow solid. Yield: 16.0 g, 57.7 mmol, 69%. LCMS m/z 278.5 (M+1). 1H NMR (500 MHz, CDCl3) δ 1.49 (br s, 9H), 2.23 (s, 3H), 3.84 (s, 3H), 6.87 (s, 1H), 7.51 (s, 1H), 7.60 (s, 1H), 8.67 (br s, 1H).

Provenance & Evidence