Diisopropylethylamine → (S)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-3-cyclopentyl-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (prepared as in Example 26, 150 mg, 0.43 mmol) in dichloromethane (10 mL) was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 75 mg, 0.48 mmol), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (230 mg, 0.52 mmol) and N,N-diisopropylethylamine (170 mg, 1.30 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, saturated sodium chloride solution and dried. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes) to afford (S)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (47 mg, 22%) as a white solid: LR-ES-MS m/z calculated for C26H34N4O5 [M]+ 482, observed [M+H]+ 483; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00-1.94 (m, 11H) 1.04 (br. s., 3H) 1.06 (br. s., 3H) 3.81 (s, 3H) 3.89 (s, 2H) 4.13 (d, J=18.4 Hz, 1H) 4.52 (d, J=18.4 Hz, 1H) 4.68 (s, 1H) 4.70 (s, 1H) 4.81 (dd, J=10.4, 4.7 Hz, 1H) 6.44 (d, J=2.2 Hz, 1H) 6.95-7.05 (m, 1H) 7.18-7.24 (m, 1H) 7.25-7.36 (m, 2H) 7.53 (d, J=2.2 Hz, 1H) 10.79 (s, 1H).

Provenance & Evidence