Triphenylphosphine → HCID 67682397, Verbindung

HRID 1751589Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1751589
Br[C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[CH:8][C:9]([C:17]4[NH:21][C:20]([C@@H:22]5[CH2:26][CH2:25][CH2:24][N:23]5[C:27](=[O:37])[C@@H:28]([NH:32][C:33](=[O:36])[O:34][CH3:35])[CH:29]([CH3:31])[CH3:30])=[N:19][CH:18]=4)=[CH:10][C:11]=3[C:12]2([F:16])[F:15])=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:46]2[CH:47]=[CH:48][C:49]3[N:53]=[C:52]([C@@H:54]4[C@@H:59]5[CH2:60][C@@H:56]([CH2:57][CH2:58]5)[N:55]4[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[NH:51][C:50]=3[CH:68]=2)O1.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:16][C:12]1([F:15])[C:13]2[CH:14]=[C:2]([C:47]3[CH:46]=[CH:68][C:50]4[N:51]=[C:52]([C@@H:54]5[C@@H:59]6[CH2:60][C@@H:56]([CH2:57][CH2:58]6)[N:55]5[C:61]([O:63][C:64]([CH3:66])([CH3:65])[CH3:67])=[O:62])[NH:53][C:49]=4[CH:48]=3)[CH:3]=[CH:4][C:5]=2[C:6]2[C:11]1=[CH:10][C:9]([C:17]1[NH:21][C:20]([C@@H:22]3[CH2:26][CH2:25][CH2:24][N:23]3[C:27](=[O:37])[C@@H:28]([NH:32][C:33]([O:34][CH3:35])=[O:36])[CH:29]([CH3:30])[CH3:31])=[N:19][CH:18]=1)=[CH:8][CH:7]=2

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 67506198(1R,3S,4S)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylateHCID 67522673HCID 67522673, Verbindung

Produkt 1

HCID 67682397HCID 67682397, VerbindungAusbeute 76,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A mixture of methyl (S)-1-((S)-2-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (192 mg, 0.33 mmol), (1R,3S,4S)-tert-butyl 3-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (177 mg, 0.40 mmol), 1M aqueous sodium bicarbonate solution (1.27 mL, 1.27 mmol), triphenylphosphine (9 mg, 0.03 mmol), palladium(II) acetate (4 mg, 0.02 mmol) and dimethoxyethane (3.5 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 (1R,3S,4S)-tert-butyl 3-(6-(9,9-difluoro-7-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-9H-fluoren-2-yl)-1H-benzo[d]imidazol-2-yl)-2-azabicyclo[2.2.1]heptane-2-carboxylate (204 mg, 76%).

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-aaba04296d0642ef8938977f7771ac19
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156823B2

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