4-Methylmorpholine → phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

4-Methylmorpholine (73.6 μl, 0.670 mmol) was added into the solution of (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (300 mg, 0.558 mmol) and 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium (220 mg, 0.670 mmol) in acetonitrile (9.3 ml). The resulting solution was cooled to 0° C., and it was stirred at 0° C. for 15 min. To the reaction mixture was added 6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinamine (139 mg, 0.670 mmol). After stirring for 2 days at ambient temperature, the reaction mixture was concentrated to yield a residue. The residue was dissolved in DCM, and the resulting solution was washed with Na2SO4 (sat.) and brine. The solvent was removed to give a residue again. The residue was purified by RP-HPLC to give an impure product. The impure product was purified by using Silica Gel chromatography (DCM/MeOH/NH4OH=9/1/0.002) to yield phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({6-[(2R)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino) carbonyl]-1-pyrazolidinecarboxylate (71 mg, 0.098 mmol, 18% yield). MS (ES+) m/z 727.1 (MH+).

Provenance & Evidence