Propargyl alcohol → methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxyprop-1-ynyl)benzoate

HRID 1627286Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1627286
Br[C:2]1[CH:11]=[CH:10][C:9]([CH2:12][S:13][C:14]2[N:15]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([O:37][CH3:38])[CH:31]=3)[C:16]([C:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=3)([CH3:21])[CH3:20])=[CH:17][N:18]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH2:39]([OH:42])[C:40]#[CH:41].N1CCCC1>CCOC(C)=O.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:29][C:24]1[CH:23]=[C:22]([C:19]([C:16]2[N:15]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([O:37][CH3:38])[CH:31]=3)[C:14]([S:13][CH2:12][C:9]3[CH:10]=[CH:11][C:2]([C:41]#[C:40][CH2:39][OH:42])=[C:3]([CH:8]=3)[C:4]([O:6][CH3:7])=[O:5])=[N:18][CH:17]=2)([CH3:21])[CH3:20])[CH:27]=[CH:26][C:25]=1[Cl:28]

Komponenten

7

Edukt 3

HCID 7859Propargyl alcoholHCID 31268PyrrolidineHCID 66740663HCID 66740663, Verbindung

Produkt 1

HCID 66740390methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxyprop-1-ynyl)benzoateAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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+)KatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of methyl 2-bromo-5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)benzoate (506 mg, 0.79 mmol, 1.0 eq), propargyl alcohol (0.07 mL, 1.2 mmol, 1.5 eq) and pyrrolidine (0.1 mL, 1.2 mmol, 1.5 eq) in dry, degassed DMF (4 mL) was added PdCl2(dppf)2 (30 mg, 0.04 mmol, 5 mol %) and CuI (15 mg, 0.08 mmol, 10 mol %). The reaction mixture was heated at 80° C. for 5 h at which time LCMS showed 85% conversion. The mixture was diluted with EtOAc, washed with brine, dried and concentrated. Purification by column chromatography (0 to 75% EtOAc/Hexanes) provided 378 mg (78% yield) of methyl 5-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-2-(3-hydroxyprop-1-ynyl)benzoate. MS (EI) m/z 615 (MH+).

Aufarbeitung

  1. customdegassed DMF (4 mL)
  2. washwashed with brine
  3. customdried
  4. concentrationconcentrated
  5. customPurification by column chromatography (0 to 75% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-2eb7c2c9074e451b97456a3b88577e2b
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785488B2

Notizen zur Reaktion

Wird geladen…