Triphenylphosphine → HCID 67682549, Verbindung

HRID 1751591Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751591
[CH3:1][CH:2]([CH3:36])[C@H:3]([NH:31][C:32](=[O:35])[O:33][CH3:34])[C:4](=[O:30])[N:5]1[C@H:10]([C:11]2[NH:15][C:14]3[CH:16]=[C:17](B4OC(C)(C)C(C)(C)O4)[CH:18]=[CH:19][C:13]=3[N:12]=2)[C@@H:9]2[CH2:29][C@H:6]1[CH2:7][CH2:8]2.Br[C:38]1[CH:50]=[C:49]2[C:41]([C:42]3[CH:43]=[CH:44][C:45]([C:53]4[NH:57][C:56]([C@@H:58]5[CH2:62][CH2:61][CH2:60][N:59]5[C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])=[N:55][CH:54]=4)=[CH:46][C:47]=3[C:48]2([F:52])[F:51])=[CH:40][CH:39]=1.C(=O)(O)[O-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(COC)OC>[F:52][C:48]1([F:51])[C:47]2[CH:46]=[C:45]([C:53]3[NH:57][C:56]([C@@H:58]4[CH2:62][CH2:61][CH2:60][N:59]4[C:63]([O:65][C:66]([CH3:68])([CH3:67])[CH3:69])=[O:64])=[N:55][CH:54]=3)[CH:44]=[CH:43][C:42]=2[C:41]2[C:49]1=[CH:50][C:38]([C:17]1[CH:18]=[CH:19][C:13]3[N:12]=[C:11]([C@@H:10]4[C@@H:9]5[CH2:29][C@@H:6]([CH2:7][CH2:8]5)[N:5]4[C:4](=[O:30])[C@@H:3]([NH:31][C:32]([O:33][CH3:34])=[O:35])[CH:2]([CH3:36])[CH3:1])[NH:15][C:14]=3[CH:16]=1)=[CH:39][CH:40]=2

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 59610218HCID 59610218, VerbindungHCID 67682542HCID 67682542, Verbindung

Produkt 1

HCID 67682549HCID 67682549, VerbindungAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A mixture of methyl (S)-3-methyl-1-oxo-1-((1R,3S,4S)-3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)butan-2-ylcarbamate (122 mg, 0.25 mmol), (S)-tert-butyl 2-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (127 mg, 0.25 mmol), 1M aqueous sodium bicarbonate solution (0.93 mL, 0.93 mmol), triphenylphosphine (13 mg, 0.05 mmol), palladium(II) acetate (5.5 mg, 0.02 mmol) and dimethoxyethane (2.5 mL) was degassed with a stream of argon for twenty minutes. The reaction was heated to 95° C. After four hours, the reaction was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with saturated aqueous NaHCO3 solution and brine, dried (Na2SO4) and concentrated. The crude material was purified by flash column chromatography to yield (S)-tert-butyl 2-(5-(9,9-difluoro-7-(2-((1R,3S,4S)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[2.2.1]heptan-3-yl)-1H-benzo[d]imidazol-6-yl)-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (106 mg, 54%).

Aufarbeitung

  1. customwas degassed with a stream of argon for twenty minutes
  2. temperaturethe reaction was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe organic phase was washed with saturated aqueous NaHCO3 solution and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-2ee67e528a32408892aa47a55a440dbc
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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