1,2-Oxazole-5-carboxylic acid → N-[[3-[1,2,3,4,4a,5-hexahydro-3-(5 isoxazolylcarbonyl)pyrazino[2,1-c][1,4]benzoxazin-8-yl]-2-oxo-5-(S)-oxazolidinyl]methyl]-acetamide

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Reaction Steps

To a flask containing 8-[5-(S)-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]-1, 2, 4a, 5-tetrahydropyrazino[2, 1-c] [1, 4]benzoxazine-3(4H)-carboxylic acid phenylmethyl ester (EXAMPLE 1, 150 mg, 0.31 mmol) in methanol (5 mL) and methylene chloride (5 mL) is introduced 10% palladium on carbon (70 mg). The mixture is placed under a hydrogen balloon for 17 hours, filtered through celite, and concentrated in vacuo. The residue is dissolved in pyridine (5 mL) followed by the addition of isoxazole-5-carboxylic acid (40 mg, 0.35 mmol), 4-dimethylaminopyridine (5 mg, 0.04 mmol), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(70 mg, 0.35 mmol). The reaction is stirred under an inert atmosphere for 17 hours, diluted with methylene chloride (20 mL), washed with 1N HCl (20 mL) and saline, dried over Na2SO4, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with chloroform/methanol (97/3). The appropriate fractions are combined (Rf =0.42, TLC, chloroform/methanol, 90/10) and concentrated in vacuo to give the title compound, HRMS calcd for C21H23N5O6 : 441.1648. Found: 441.1658.

Provenance & Evidence