4-Methylmorpholine → phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl) heptanoyl]-1-pyrazolidinecarboxylate

Participants

Reaction Steps

To a solution of (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (1.015 g, 1.931 mmol) in acetonitrile (30 mL) at 0° C. was added 4-methylmorpholine (0.467 mL, 4.25 mmol), followed by 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium tetrafluoroborate (DMTMM) (0.559 g, 2.317 mmol). The solution was stirred for 15 min, then 5-fluoro-2-pyridinamine (0.260 g, 2.317 mmol) was added. The reaction mixture was warmed up to room temperature and stirred overnight. The solvent was evaporated, and the residue was dissolved in DCM. The solution was washed with 5% aq. NaHSO4 followed by water, and the organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford a crude oil which was purified by RP-HPLC to yield phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-pyrazolidinecarboxylate as a colorless gum (830 mg, 69%). LCMS: (M+H)+: 620.2.

Provenance & Evidence