Propargyl alcohol → 2-Amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(4-hydroxybut-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one

HRID 30575

Reaktionsgleichung

Reaktionsgleichung von HRID 30575
[C:1](P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(NC(C)C)(C)C.[NH2:21][C:22]1[N:26]([CH3:27])[C:25](=[O:28])[C:24]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41](Br)[CH:40]=2)([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[CH:31][CH:30]=2)[N:23]=1.[OH:46][CH2:47][C:48]#[CH:49]>O1CCOCC1.[Cu](I)I.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.O>[NH2:21][C:22]1[N:26]([CH3:27])[C:25](=[O:28])[C:24]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH:36]([F:38])[F:37])=[CH:31][CH:30]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([C:1]#[C:49][CH2:48][CH2:47][OH:46])[CH:40]=2)[N:23]=1

Komponenten

9

Edukt 4

HCID 7859Propargyl alcoholHCID 7912DiisopropylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 597903072-amino-4-(3-bromophenyl)-4-(4-(difluoromethoxy)phenyl)-1-methyl-1H-imidazol-5(4H)-one

Produkt 1

HCID 161141522-Amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(4-hydroxybut-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-oneAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 83717Copper iodideKatalysatorHCID 498840Bis(benzonitrile)palladium chlorideKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
35 °C

Versuchsvorschrift

A mixture of copper iodide (8 mg, 0.04 mmol), bis(benzonitrile)dichloro palladium(II) (23 mg, 0.06 mmol) and anhydrous dioxane under argon was stirred for 3 min., treated with tri-t-butyl phosphine (10% in hexane) (240 mg, 0.12 mmol), stirred for 5 min. treated with diisopropyl amine (0.33 mL, 2.4 mmol) followed by a solution of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (0.82 g, 2 mmol) in dioxane and 1-hydroxy-2-propyne (0.47 mL, 0.006 mmol). The reaction mixture was heated to 35° C. for 30 min., poured into water and extracted with ethyl acetate. The extracts were combined, washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The resultant residue was purified by flash chromatography on silica gel, 1st in ethyl acetate 2nd 5% methanol/ethyl acetate as eluent to afford the title compound as a white solid, 0.39 g (48% yield), mp 90-93° C.; 1H NMR (DMSO-d6) δ 2.5 ((2H, under DMSO peak); 2.95 (s, 3 H); 3.5 (q, 2 H); 4.8 (t, 1 H); 6.6 (b, 2H); 7.1 (d, 2H); 7.15 (t, 2F); 7.2 (m, 2 H); 7.3 (m, 4 H); MS [(+)ESI] m/z=400.2 [M−H]+.

Aufarbeitung

  1. stirringstirred for 5 min.
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by flash chromatography on silica gel, 1st in ethyl acetate 2nd 5% methanol/ethyl acetate as eluent

Quellen und Nachweise

ORD-Eintrag
ord-e1700d82ac8d44c18148b7514ef11cb0
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423158B2

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