Morpholine → HCID 58641332, compound

Participants

Reaction Steps

A solution of methyl N-{(1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl}-β-alaninate (40-1, 84 mg, 0.19 mmol, 1 equiv) and sodium hydroxide (1N, 0.57 mL, 0.57 mmol, 3.00 equiv) in t-BuOH (4 mL) was stirred at 23 deg C. for 4 h. The reaction mixture was concentrated and the residue was partitioned between brine adjusted to pH 4 with aqueous 1 N HCL solution and ethyl acetate (2×40 mL). The combined organic layers were dried over sodium sulfate and concentrated. A solution of the residue, morpholine (0.083 mL, 0.95 mmol, 5.0 equiv), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 73 mg, 0.38 mmol, 2.0 equiv), and 1-hydroxy-7-azabenzotriazole (52 mg, 0.38 mmol, 2.0 equiv) in DMF (2 mL) was heated at 50° C. for 20 h. The reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution and ethyl acetate (2×30 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TFA present) and the desired fractions partitioned between saturated sodium bicarbonate solution and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to provide N-{(1S)-1-cyclopropyl-2-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]-2-oxoethyl}-3-morpholin-4-yl-3-oxopropan-1-amine (41-2) as a white foam. LRMS m/z M+H) 496.5 found, 496.2 required.

Provenance & Evidence