Potassium Carbonate → HCID 178502495, Verbindung

HRID 1413028Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1413028
[CH3:1][CH:2]([CH3:46])[C@H:3]([NH:42][C:43](=[O:45])[O-:44])[C:4]([N:6]1[C@H:10]([C:11]2[NH:15][C:14]3[C:16]4[C:21]([CH:22]=[CH:23][C:13]=3[N:12]=2)=[CH:20][C:19]2[C:24]3[C:29]([CH2:30][O:31][C:18]=2[CH:17]=4)=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=3)[CH2:9][CH2:8][C@@H:7]1[CH3:41])=[O:5].Br[C:48]1[NH:52][C:51]([C@@H:53]2[CH2:57][C@H:56]([CH3:58])[CH2:55][N:54]2[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][CH:49]=1.[C:66](=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:66][O:44][C:43]([NH:42][C@H:3]([C:4]([N:6]1[C@@H:7]([CH3:41])[CH2:8][CH2:9][C@H:10]1[C:11]1[NH:15][C:14]2[C:16]3[C:21]([CH:22]=[CH:23][C:13]=2[N:12]=1)=[CH:20][C:19]1[C:24]2[C:29]([CH2:30][O:31][C:18]=1[CH:17]=3)=[CH:28][C:27]([C:48]1[NH:52][C:51]([C@@H:53]3[CH2:57][C@H:56]([CH3:58])[CH2:55][N:54]3[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][CH:49]=1)=[CH:26][CH:25]=2)=[O:5])[CH:2]([CH3:1])[CH3:46])=[O:45]

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 69675472HCID 69675472, VerbindungHCID 178448384HCID 178448384, Verbindung

Produkt 1

HCID 178502495HCID 178502495, VerbindungAusbeute 63,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of [(2S)-3-methyl-1-{(2S,5S)-2-methyl-5-[9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]pyrrolidin-1-yl}-1-oxobutan-2-yl]carbamate (269 mg, 0.42 mmol), (2S,4S)-tert-butyl 2-(5-bromo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate (206 mg, 0.54 mmol), tetrakis(triphenylphosphine) palladium(0) (49 mg, 0.042 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (31 mg, 0.042 mmol) in DMSO (3 mL) and dioxanes (3 mL) was added a solution of potassium carbonate (2M in water, 0.69 mL, 1.39 mmol). The resulting mixture was degassed and then heated to 95° C. for 2 h. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with saturated sodium bicarbonate and brine, dried over Na2SO4 and concentrated. The crude residue was purified by flash chromatography (1 to 20% MeOH/EtOAc) to yield tert-butyl(2S,4S)-2-[5-(2-{(2S,5 S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-methylpyrrolidine-1-carboxylate (202 mg, 63%).

Aufarbeitung

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction was diluted with ethyl acetate
  4. washThe organics were washed with saturated sodium bicarbonate and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography (1 to 20% MeOH/EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-1109d8eef1ba45589d0822dac62e492c
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921341B2

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