4-Methylmorpholine → (3R)-3-(cyclopentyl methyl)-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxo-N-[(phenylmethyl)oxy]butanamide

Participants

Reaction Steps

To a solution of (3R)-3-(cyclopentylmethyl)-4-[5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxobutanoic acid (212 mg, 0.58 mmol) in dichloromethane (DCM) (10 ml) was added O-(phenylmethyl)hydroxylamine (93 mg, 0.75 mmol), 4-methylmorpholine (0.17 ml, 1.5 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (79 mg, 0.58 mmol), and N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (133 mg, 0.70 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature and was stirred for 5 hours. The reaction mixture was then washed with water (15 mL) and NaHCO3 solution (15 mL×3), and concentrated to provide the crude product as a mixture of diastereomers. This mixture was purified by Gilson HPLC (Sunfire Column 19×50 mm, flowrate 25 mL/min, 10 min, 5-65% MeCN:H2O) to afford (3R)-3-(cyclopentyl methyl)-4-[(5S)-5-(4-morpholinylcarbonyl)-4,5-dihydro-1H-pyrazol-1-yl]-4-oxo-N-[(phenylmethyl)oxy]butanamide (57 mg, 21% yield). MS: 472 ([M+H]+).

Provenance & Evidence