Water → HCID 178502381, Verbindung

HRID 1500513Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1500513
[CH3:1][O:2][C:3](=[O:36])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].Br[C:38]1[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][C:39]=1[O:45][C:46]([F:49])([F:48])[F:47].O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[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>[CH3:1][O:2][C:3](=[O:36])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:38]3[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][C:39]=3[O:45][C:46]([F:47])([F:48])[F:49])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 141291984-Bromo-3-(trifluoromethoxy)anilineHCID 178502353HCID 178502353, Verbindung

Produkt 1

HCID 178502381HCID 178502381, VerbindungAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of [(S)-2-methyl-1-((S)-2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (1.80 g, 3.63 mmol) and 4-bromo-3-trifluoromethoxy-phenylamine (1.00 g, 3.90 mmol) dissolved in toluene (5.4 mL) and water (2.7 mL) was added potassium carbonate (2.50 g, 18.1 mmol). The reaction mixture was sparged with nitrogen. Tetrakis(triphenylphosphine)-palladium(0) (0.21 g, 0.18 mmol) was added and the reaction mixture was sparged with nitrogen and heated at 100° C. in a sealed tube overnight, diluted in ethyl acetate (100 mL) and washed with water, brine. The organic layer was dried over sodium sulfate, filtered, and concentrated to produce a red paste (6.5 g), which was purified by silica gel chromatography (120 g silica, 0-3% MeOH/DCM) to provide the title intermediate (1.05 g) and a second fraction which was purified by reverse phase HPLC to provide the di-TFA salt of the title intermediate (800 mg). (Total yield 80%).

Aufarbeitung

  1. customThe reaction mixture was sparged with nitrogen
  2. customthe reaction mixture was sparged with nitrogen
  3. additiondiluted in ethyl acetate (100 mL)
  4. washwashed with water, brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto produce a red paste (6.5 g), which
  9. customwas purified by silica gel chromatography (120 g silica, 0-3% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-9ddbb592361b40ddb36551aab4146539
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206159B2

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