Pyrrolidine → 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine

HRID 83840

Reaktionsgleichung

Reaktionsgleichung von HRID 83840
Br[C:2]1[CH:33]=[C:32]([F:34])[C:5]([CH2:6][S:7][C:8]2[N:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:10]([C:13]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([O:23][CH3:24])[CH:17]=3)([CH3:15])[CH3:14])=[CH:11][N:12]=2)=[C:4]([F:35])[CH:3]=1.[CH3:36][N:37]([CH3:41])[CH2:38][C:39]#[CH:40].N1CCCC1>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].[Cu]I>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:13]([C:10]2[N:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:8]([S:7][CH2:6][C:5]3[C:32]([F:34])=[CH:33][C:2]([C:40]#[C:39][CH2:38][N:37]([CH3:41])[CH3:36])=[CH:3][C:4]=3[F:35])=[N:12][CH:11]=2)([CH3:15])[CH3:14])=[CH:17][C:18]=1[O:23][CH3:24]

Komponenten

6

Edukt 3

HCID 31268PyrrolidineHCID 81643N,N-DimethylpropargylamineHCID 667405782-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

Produkt 1

HCID 672365113-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amineAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (250 mg, 0.43 mmol, 1.0 eq), N,N-dimethylprop-2-yn-1-amine (0.07 mL, 0.64 mmol, 1.5 eq) and pyrrolidine (0.05 mL, 0.64 mmol, 1.5 eq) in dry, degassed DMF (2 mL) were added PdCl2(dppf)2 (16 mg, 0.022 mmol, 5 mol %) and CuI (8 mg, 0.043 mmol, 10 mol %). The reaction mixture was heated at 80° C. for 16 h, at which time LCMS showed complete consumption of starting material. The mixture was diluted with EtOAc, washed with brine, dried and concentrated. Purification by column chromatography (0 to 15% MeOH/DCM) furnished 238 mg (95% yield) of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine as a brown oil: MS (EI): 584 (MH+).

Aufarbeitung

  1. customdegassed DMF (2 mL)
  2. customconsumption of starting material
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with brine
  5. customdried
  6. concentrationconcentrated
  7. customPurification by column chromatography (0 to 15% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-23485bfa6a9a4682ae91505b2978e3ce
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846739B2

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