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

Participants

Reaction Steps

A solution of (S)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (prepared as in Example 1, 94 mg, 0.24 mmol) in a hydrochloric acid (gas) saturated acetic acid (5 mL) was heated in a sealed tube at 75° C. for 2 h. After that time the reaction mixture was cooled to room temperature, and concentrated. The residue was added to benzyl alcohol (1000 mg, 9.15 mmol), and toluene-4-sulfonic acid hydrate (10 mg), cesium chloride hexahydrate (0.3 g) on silica gel (Sabitha, G.; Reddy, M. N.; Sudhakar, K.; Yadav, J. S.; Letters Org. Chem, 2005, 2, 763-766). The mixture was stirred at room temperature for 72 h. The reaction mixture was concentrated and the residue was dissolved in dichloromethane. The organic layer was washed with saturated sodium bicarbonate solution, saturated sodium chloride solution, and dried over magnesium sulfate and purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes) to afford (S)-2-(4-benzyloxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-3-cyclopentyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (6 mg, 5%): LR-ES-MS m/z calculated for C26H34N4O4 [M]+ 466, observed [M+H]+ 467; 1H NMR (300 MHz, CDCl3) δ ppm 0.77 (br. s., 1H) 1.08 (br. s., 2H) 1.08 (br. s., 6H) 1.32-2.07 (m, 8H) 2.89 (br. s., 1H) 3.79-3.96 (m, 1H) 3.88 (br. s., 2H) 3.98-4.15 (m, 1H) 4.78 (br. s., 1H) 4.92 (br. s., 2H) 5.16 (br. s., 1H) 6.61 (br. s., 1H) 7.08-7.43 (m, 5H) 8.81 (br. s., 1H).

Provenance & Evidence