1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920103, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-[4-(3-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid (prepared as in Example 162, 300 mg, 0.90 mmol) in dichloromethane (20 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (154 mg, 0.99 mmol) and 1-hydroxybenzotriazole (128 mg, 0.95 mmol). The reaction mixture was stirred at 25° C. for 1 h followed by the addition of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 168 mg, 1.08 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The crude product obtained after concentration, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 40 g; (20% to 100% ethyl acetate/hexanes) to afford (S)-2-[4-(3-ethoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-amide (217 mg, 51%) as a yellow powder: HR-ES-MS m/z calculated for C25H34N4O5 [M+H]+ 470, observed 471; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.04 (br. s., 3H), 1.06 (br. s., 3H), 1.31 (t, J=6.8 Hz, 3H), 1.38-1.64 (m, 2H), 1.67-1.84 (m, 1H), 3.89 (s, 2H), 4.04 (q, J=6.8 Hz, 2H), 4.16 (d, J=18.1 Hz, 1H), 4.56 (d, J=18.1 Hz, 4.68 (s, 1H), 4.86 (s, 1H), 4.87-4.93 (m, 1H), 6.44 (d, J=1.8 Hz, 1H), 6.78-6.92 (m, 3H), 7.35 (t, J=8.3 Hz, 1H), 7.53 (d, J=1.8 Hz, 1H), 10.79 (s, 1H).

Provenance & Evidence