Diisopropylethylamine → (S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxamide

Participants

Reaction Steps

3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxylic acid (Intermediate B1) (100 mg, 0.390 mmol) was dissolved in DCM (10 mL) in a 40 mL screw-cap vial. (S)-2-amino-N,3,3-trimethylbutanamide (59.1 mg, 0.410 mmol) and DIEA (204 μl, 1.171 mmol) were added, followed by TBTU (132 mg, 0.410 mmol), and the reaction was stirred for 3 hours. LCMS showed complete consumption of starting material. The solution was extracted with saturated aqueous sodium bicarbonate (10 mL) and the organic layer was removed. The aqueous layer was extracted with DCM (10 ml). The combined organic extracts were dried with anhydrous sodium sulfate, filtered and evaporated under reduced pressure to a brown oil which was purified by flash chromatography (silica gel, 25% Hex/EtOAc to 100% EtOAc). Fractions were combined to yield the desired (S)—N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepine-1-carboxamide as a white solid (133 mg, 89%). LCMS (+ESI) m/z 383.2 [MH]+. 1H-NMR (CDCl3) δ 7.90 (d, 1H), 7.45-7.55 (m, 5H), 5.90 (m, 1H), 4.30 (d, 1H), 4.05 (m, 2H), 3.40 (m, 2H), 2.80 (d, 3H), 1.90 (m, 2H), 1.80 (m, 2H), 1.65 (m, 2H), 1.10 (s, 9H).

Provenance & Evidence