Potassium Carbonate → Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate

HRID 1056137Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1056137
Br[CH2:2][C:3]([C:5]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:17][CH:18]1[CH2:20][CH2:19]1)[C:9]([CH3:16])=[N:10]2)=[O:4].[C:21]([O:25][C:26]([NH:28][C@H:29]([CH3:38])[C:30](=[O:37])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C([O-])(O)=O.[Na+].C(Cl)(Cl)Cl>[C:21]([O:25][C:26]([NH:28][CH:29]([CH3:38])[C:30](=[O:37])[CH:31]([CH2:2][C:3]([C:5]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:17][CH:18]1[CH2:20][CH2:19]1)[C:9]([CH3:16])=[N:10]2)=[O:4])[C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])([CH3:23])([CH3:24])[CH3:22]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 11288402Ethyl (4R)-4-[[(1,1-dimethylethoxy)carbonyl]amino]-3-oxopentanoateHCID 897821632-Bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

Produkt 1

HCID 89781885Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoateAusbeute 98 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6212ChloroformLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

A mixture of 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (293c) (0.81 g, 2.38 mmol) and (R)-ethyl 4-((tert-butoxycarbonyl)amino)-3-oxopentanoate (602) (0.74 g, 2.86 mmol) was dissolved in DMF (7.00 mL). Then K2CO3 (Acros Organics, New Jersey) (0.82 g, 5.95 mmol) was added into the reaction mixture. The overall mixture was stirred under inert atmosphere overnight. The mixture was diluted with saturated NaHCO3 (10 mL) and CHCl3 (20 mL). The layers were separated and the aq. layer was extracted with CHCl3 (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography through an Interchim PuriFlash UP (25 micron) pre-packed silica-gel column (40 gram), eluting with a gradient of 0-30% EtOAc in DCM, to provide ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate (1.20 g, 2.32 mmol, 98% yield) as a yellow oil.

Aufarbeitung

  1. customThe layers were separated
  2. extractionthe aq. layer was extracted with CHCl3 (3×)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by chromatography through an Interchim PuriFlash UP (25 micron) pre-packed silica-gel column (40 gram)
  7. washeluting with a gradient of 0-30% EtOAc in DCM

Quellen und Nachweise

ORD-Eintrag
ord-000e2558689f4c70ae5a1e58919705f7
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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