Triethylamine → (S)-4-methyl-2-(2-oxo-4-o-tolyloxy-2,5-dihydro-pyrrol-1-yl)-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-4-methyl-2-(2-oxo-4-o-tolyloxy-2,5-dihydro-pyrrol-1-yl)-pentanoic acid (0.208 g, 0.69 mmol) in N,N-dimethylformamide (4 mL) was added 1-methyl-1H-pyrazol-3-ylamine (0.080 g, 0.82 mmol) and benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (0.620 g, 1.40 mmol). The mixture was stirred at 0° C. and triethylamine (0.150 g, 1.48 mmol) was added. The mixture was stirred at room temperature for 3 h and the solvents were evaporated. The residue was treated with ethyl acetate and ammonium chloride solution, and the organic layer separated. The organic layer was washed with brine and dried over sodium sulfate. The solvents were evaporated and the residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 25 g, 20% to 100% ethyl acetate/hexanes) which afforded (S)-4-methyl-2-(2-oxo-4-o-tolyloxy-2,5-dihydro-pyrrol-1-yl)-pentanoic acid (1-methyl-1H-pyrazol-3-yl)-amide (0.050 g, 19%) as a tan solid: HR-ES-MS m/z calculated for C21H26N4O3 [M+H]+ 383.2078, observed 383.2077, 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00-0.90 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.3 Hz, 3H), 1.20-1.92 (m, 3H), 2.19 (s, 3H), 3.73 (s, 3H), 4.20 (d, J=18.1 Hz, 1H), 4.57 (d, J=18.1 Hz, 1H), 4.63 (s, 1H), 4.87 (dd, J=10.3, 4.8 Hz, 1H), 6.40 (d, J=1.8 Hz, 1H), 7.17-7.33 (m, 3H), 7.36 (d, J=7.2 Hz, 1H), 7.55 (d, J=1.8 Hz, 1H), 10.72 (s, 1H).

Provenance & Evidence