Ethyl Acetate → N1-(cyanomethyl)-N2-{(S)-(4-fluorophenyl)[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

HRID 1009284Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1009284
[C:1]([CH2:3][NH:4][C:5](=[O:27])[C@@H:6]([NH:11][C@@H:12]([C:20]1[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=1)[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[CH2:7][CH:8]([CH3:10])[CH3:9])#[N:2].[CH3:28][S:29]([C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][CH:33]=1)(=[O:31])=[O:30].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.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]>[C:1]([CH2:3][NH:4][C:5](=[O:27])[C@H:6]([CH2:7][CH:8]([CH3:10])[CH3:9])[NH:11][C@H:12]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[C:20]1[CH:25]=[CH:24][C:23]([C:35]2[CH:36]=[CH:37][C:32]([S:29]([CH3:28])(=[O:31])=[O:30])=[CH:33][CH:34]=2)=[CH:22][CH:21]=1)#[N:2]

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27595302-(4-Methanesulfonylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86590549(2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino)-4-methylpentanoic acid cyanomethylamide

Produkt 1

HCID 59715505N1-(cyanomethyl)-N2-{(S)-(4-fluorophenyl)[4'-(methylsulfonyl)-1,1'-biphenyl-4-yl]methyl}-L-leucinamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
82.5 °C

Versuchsvorschrift

A mixture of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid cyanomethylamide (0.27 g, 0.636 mmol), 2-(4-methanesulfonylphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.177 g, 0.626 mmol) and potassium carbonate (0.703 mL of a 2.0 M solution) in DMF (5 mL) was degassed. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloromethane complex (27 mg, 0.038 mmol) was added. The reaction mixture was heated in a sealed tube at 80-85° C. for 3 hours and cooled to room temperature. Ethyl acetate (15 mL) was added. The reaction mixture was washed with brine (10 mL), saturated aqueous NaHCO3 (10 mL), brine (10 mL), filtered through a plug of MgSO4/DARCO activated charcoal/silica gel, concentrated in vacuo, and purified by preparative TLC (Chromatotron® using 5% ethyl acetate/dichloromethane to elute to give N1-(cyanomethyl)-N2-{(S)-(4-fluorophenyl) [4′-(methylsulfonyl)-1,1′-biphenyl-4-yl]methyl}-L-leucinamide.

Aufarbeitung

  1. customwas degassed
  2. temperaturecooled to room temperature
  3. washThe reaction mixture was washed with brine (10 mL), saturated aqueous NaHCO3 (10 mL), brine (10 mL)
  4. filtrationfiltered through a plug of MgSO4/DARCO
  5. concentrationconcentrated in vacuo
  6. custompurified by preparative TLC (Chromatotron®
  7. washto elute

Quellen und Nachweise

ORD-Eintrag
ord-1cf5ec6f9d3745288bc63b203126d335
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07973037B2

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