3-((2-Ethoxy-3,4-dioxocyclobut-1-en-1-yl)amino)-2-hydroxy-N,N-dimethylbenzamide → 3-(4-Hydroxy-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-5-ylamino)-4-{[(5-methylfuran-2-yl)-(3-methyloxetan-3-yl)methyl]amino}cyclobut-3-ene-1,2-dione

Participants

Reaction Conditions

Reaction Steps

287 mg (1.58 mmol) of C-(5-methylfuran-2-yl)-C-(3-methyloxetan-3-yl)methylamine in 3 ml of methanol were added to a suspension of 235 mg (0.78 mmol) of 3-(2-ethoxy-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N,N-dimethylbenzamide in 20 ml of methanol at 55° C. The reaction medium was heated at 55° C. for 24 hours and then concentrated to dryness. The residue was chromatographed on silica gel (40 g prepacked column, 30 ml/min, 100% dichloromethane then 4% of methanol). A residue of 130 mg was obtained and was purified by preparative TLC (eluent: 50/50/1 ethyl acetate/acetone/water). 52 mg were obtained and then precipitated from dimethyl sulfoxide and filtered off 15 mg of product were obtained in the form of a white solid. Yield=4%, HPLC=98.56%

Provenance & Evidence