Diisopropylethylamine → (2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate

HRID 659828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 659828
Cl.[Cl:2][C:3]1[C:4]([O:15][C@H:16]2[CH2:20][NH:19][C@H:18]([C:21]([O:23][CH3:24])=[O:22])[CH2:17]2)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][CH:9]=[C:8]([O:13][CH3:14])[CH:7]=2.[CH3:25][C:26]([CH3:44])([CH3:43])[C@@H:27]([C:40](O)=[O:41])[NH:28][C:29]([O:31][C@@H:32]1[CH2:34][C@H:33]1[CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39])=[O:30].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH3:25][C:26]([CH3:44])([CH3:43])[C@@H:27]([C:40]([N:19]1[CH2:20][C@H:16]([O:15][C:4]2[C:3]([Cl:2])=[N:12][C:11]3[C:6](=[CH:7][C:8]([O:13][CH3:14])=[CH:9][CH:10]=3)[N:5]=2)[CH2:17][C@H:18]1[C:21]([O:23][CH3:24])=[O:22])=[O:41])[NH:28][C:29]([O:31][C@@H:32]1[CH2:34][C@H:33]1[CH2:35][CH2:36][CH2:37][CH:38]=[CH2:39])=[O:30]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59287076L-Valine, 3-methyl-N-[[[(1R,2R)-2-(4-penten-1-yl)cyclopropyl]oxy]carbonyl]-HCID 78358295Methyl (2S)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-2-carboxylate hydrochloride

Produkt 1

HCID 78358296(2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylateAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

A solution (0.2 M) of methyl (4R)-4-[(3-chloro-7-methoxyquinoxalin-2-yl)oxy]-L-prolinate hydrochloride in DMF was treated with 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valine (1.1 eq), DIEA (5 eq) and HATU (1.2 eq). The resulting mixture was stirred at 20° C. for 5 h, then diluted with EtOAc. The organic layer was separated and washed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine. The dried organic phase was concentrated under reduced pressure to give a residue that was purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether) to furnish the title compound (96%) as an oil. MS (ES+) m/z 604 (M+H)+

Aufarbeitung

  1. customThe organic layer was separated
  2. washwashed with aqueous HCl (1 N), saturated aqueous NaHCO3 and brine
  3. concentrationThe dried organic phase was concentrated under reduced pressure
  4. customto give a residue that
  5. customwas purified by flash chromatography (eluent 10-30% EtOAc/petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-564de583833948feb3a913c56edcf3dd
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08080654B2

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