4-Methylmorpholine → 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate

Participants

Reaction Steps

To a solution of 1-{(2R)-2-(cyclopentylmethyl)-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoyl}-4,5-dihydro-1H-pyrazole-5-carboxylic acid (352 mg, 1.0 mmol) in acetonitrile (10 mL) at 0° C. was added 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (656 mg, 2.0 mmol) and N-methylmorpholine (0.28 mL, 2.5 mmol). The reaction mixture was stirred for 2 hours. After this time, 6-ethyl-2-pyridinamine (159 mg, 1.3 mmol) was added to the mixture, which was then allowed to warm to room temperature and stirred for 3 hours. The solvent was removed under reduced pressure, and water (5 mL) and DCM (15 mL) were added to the resulting residue. The phases were separated. The aqueous phase was extracted twice with DCM (15 mL), and the combined organic phases were dried over sodium sulfate and concentrated. The crude product residue was purified by Combiflash silica gel chromatography (0-100% EtOAc in hex) to provide 1,1-dimethylethyl (3R)-3-(cyclopentylmethyl)-4-(5-{[(6-ethyl-2-pyridinyl)amino]carbonyl}-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoate (359 mg, 0.79 mmol, 79% yield) as a clear oil. MS: 457 ([M+H]+).

Provenance & Evidence