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

HRID 869788

Reaktionsgleichung

Reaktionsgleichung von HRID 869788
[C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[C:4]([O-:6])=O.Cl.[CH3:11][O:12][C:13](=[O:18])[C@H:14]([CH2:16][SH:17])[NH2:15].CCN=C=NCCCN(C)C.CN1CCOCC1>CC#N.CCOC(C)=O>[SH:17][CH2:16][C@H:14]([NH:15][C:4](=[O:6])/[CH:3]=[CH:2]/[C:1]([O:8][CH3:9])=[O:7])[C:13]([O:12][CH3:11])=[O:18]

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2733208L-Cysteine, methyl ester, hydrochlorideHCID 21721168(E)-4-methoxy-4-oxobut-2-enoate

Produkt 1

HCID 86655430(R,E)-methyl 4-(3-mercapto-1-methoxy-1-oxopropan-2-ylamino)-4-oxobut-2-enoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  1. washThe organic layer was washed with saturated aqueous NaHCO3 and brine
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-4291ff60cc144a75a5d71713ee327fd4
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969354B2

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