Sodium Carbonate → (1H-benzo[d]imidazol-2-yl)(4-(3-(4,4-difluorocyclohex-1-enyl)pyrazin-2-yloxy)phenyl)methanone

HRID 555848Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 555848
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:24](Cl)=[N:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11].[F:26][C:27]1([F:42])[CH2:32][CH2:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH2:28]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:19]2[C:24]([C:30]3[CH2:31][CH2:32][C:27]([F:42])([F:26])[CH2:28][CH:29]=3)=[N:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11]

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 46207940(4-(3-chloropyrazin-2-yloxy)phenyl)(1H-benzo[d]imidazol-2-yl)methanoneHCID 593513932-(4,4-Difluorocyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Produkt 1

HCID 59351172(1H-benzo[d]imidazol-2-yl)(4-(3-(4,4-difluorocyclohex-1-enyl)pyrazin-2-yloxy)phenyl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

To a round bottomed flask was added (1H-benzo[d]imidazol-2-yl)(4-(3-chloropyrazin-2-yloxy)phenyl)methanone (0.5018 g, 1.431 mmol), 2-(4,4-difluorocyclohex-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.698 g, 2.86 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (0.080 g, 0.114 mmol), and sodium carbonate (0.455 g, 4.29 mmol) in DME (3.58 mL) and water (1.192 mL) at 80° C. to stir overnight. Upon completion, solvent was removed. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Synergi column, 4 micron, MAX-RP, 80 Å, 150×30 MM, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 15 min to provide (1H-benzo[d]imidazol-2-yl)(4-(3-(4,4-difluorocyclohex-1-enyl)pyrazin-2-yloxy)phenyl)methanone. MS (ESI, pos. ion) m/z: 433.0 (M+1). IC50 (uM) +++++.

Aufarbeitung

  1. customUpon completion, solvent was removed
  2. customThe crude product was purified by reverse-phase preparative HPLC
  3. customover 15 min

Quellen und Nachweise

ORD-Eintrag
ord-83318dbca0b948bab834c45c96b186fe
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08053438B2

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