4-Methylmorpholine → (R,E)-methyl 4-(3-mercapto-1-methoxy-1-oxopropan-2-ylamino)-4-oxobut-2-enoate

Participants

Reaction Steps

Separately, mono methyl fumarate (100 mg, 0.77 mmol) was taken up in 4 mL of CH3CN along with L-cysteine methyl ester hydrochloride (132 mg, 0.77 mmol), EDCI (245 mg, 0.77 mmol) and N-methylmorpholine (85 μL, 0.77 mmol). The reaction mixture was stirred at room temperature for 3 h. It was then diluted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3 and brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure to afford crude (R,E)-methyl 4-(3-mercapto-1-methoxy-1-oxopropan-2-ylamino)-4-oxobut-2-enoate. This material was then taken up in 3 mL of CH3CN along with (4Z,7Z,10Z,13Z,16Z,19Z)—N-(2-(2,5-dioxo-2H-pyrrol-1(5H)-yl)ethyl)docosa-4,7,10,13,16,19-hexaenamide (173 mg, 0.38 mmol) and stirred at room temperature for 30 min. The reaction mixture was then concentrated under reduced pressure. Purification by chromatography (CH2Cl2) afforded 60 mg of (E)-methyl 4-((R)-3-(1-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethyl)-2,5-dioxopyrrolidin-3-ylthio)-1-methoxy-1-oxopropan-2-ylamino)-4-oxobut-2-enoate (22%). MS (EI) calcd for C37H51N3O8S: 697.34. found: 698 (M+1).

Provenance & Evidence