1-Methylimidazole → phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[(4-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

1-Methylimidazole (1.78 mL, 22.3 mmol) was added into a solution of (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (4 g, 7.4 mmol) in dichloromethane (50.8 mL). The resulting solution was cooled to 0° C., and then methanesulfonyl chloride (0.6 mL, 7.8 mmol) was added dropwise at 0° C. To the reaction mixture was added 4-pyrimidinamine (849 mg, 8.9 mmol) and stirring continued for 1.5 h at ambient temperature. The reaction solution was filtered to remove unreacted 4-pyrimidinamine, and the filtrate was concentrated to provide a residue. The residue was dissolved in a mixed solution of ethyl acetate and acetonitrile, and was purified by silica gel chromatography (CombiFlash; Column: 220 g; 0-85% ethyl acetate in hexane; 60 min). The solvent was removed under reduced pressure to yield the desired product, phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[(4-pyrimidinylamino)carbonyl]-1-pyrazolidinecarboxylate (4.22 g, 92% yield). (ES+) m/z 615.2 (MH+).

Herkunft & Nachweise