1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57920059, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclopentyl-propionic acid (200 mg, 0.53 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (90 mg, 0.58 mmol) and 1-hydroxybenzotriazole (75 mg, 0.55 mmol). The reaction mixture was stirred at 25° C. for 2 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, 94 mg, 0.61 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, a saturated sodium chloride solution and dried over magnesium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane) to afford (S)-2-[4-(2-chloro-3-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (147 mg, 54%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04 (br. s., 3H) 1.06 (br. s., 3H) 1.08-1.95 (m, 11H) 3.89 (br. s., 2H) 3.90 (s, 3H) 4.21 (d, J=18.4 Hz, 1H) 4.59 (d, J=18.4 Hz, 1H) 4.67 (s, 1H) 4.80 (s, 1H) 4.81-4.87 (m, 1H) 6.45 (d, J=2.1 Hz, 1H) 7.09 (d, J=8.2 Hz, 1H) 7.13 (d, J=8.5 Hz, 1H) 7.41 (t, J=8.5 Hz, 1H) 7.53 (d, J=2.1 Hz, 1H) 10.80 (s, 1H).

Provenance & Evidence