Sodium Carbonate → 2-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydro-imidazol-4-one

HRID 643478Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 643478
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:20][C:21]1[N:25]([CH3:26])[C:24](=[O:27])[C:23]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[C:42](Br)[CH:41]=2)([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[C:30]([F:39])[CH:29]=2)[N:22]=1.[N:48]1[CH:53]=[C:52](B(O)O)[CH:51]=[N:50][CH:49]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.COCCOC>[NH2:20][C:21]1[N:25]([CH3:26])[C:24](=[O:27])[C:23]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[C:42]([C:52]3[CH:53]=[N:48][CH:49]=[N:50][CH:51]=3)[CH:41]=2)([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[C:30]([F:39])[CH:29]=2)[N:22]=1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 575312642-Amino-5-(3-bromo-4-fluorophenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydroimidazol-4-one

Produkt 1

HCID 575313272-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydro-imidazol-4-oneAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A mixture of ethylene glycol dimethyl ether, tris(dibenzylideneacetone)-dipalladium(0) (0.015 g, 16.5 μmol) and triphenylphosphine (0.008 g, 32.0 μmol) under nitrogen is stirred for 5 min, treated with 2-amino-5-(3-bromo-4-fluorophenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydroimidazol-4-one (0.154 g, 0.33 mmol), 5-pyrimidine boronic acid (0.046 g, 0.37 mmol), sodium carbonate (0.105 g, 0.99 mmol) and water, heated at reflux temperature for 1.25 h, cooled to room temperature and concentrated in vacuo. The resultant residue is purified by flash chromatography (silica, 95:5:0.5 methylene chloride/methanol/concentrated ammonium hydroxide as eluent) to afford a viscous oil. This oil is suspended in a mixture of methylene chloride/hexanes and concentrated to afford the title compound as an off-white solid, 0.045 g (29% yield), mp 102-110° C., identified by HNMR and mass spectral analyses. 1H NMR (500 MHz, CD3OD) δ 9.15 (s, 1H), 8.95 (s, 2H), 7.62-7.56 (m, 2H), 7.39-7.27 (m, 4H), 3.12 (s, 3H); IR 3353, 3061, 2956, 1732, 1668, 1498, 1470, 1416, 1251, 1216, 1170 cm−1; ESI MS m/z 464 [C21H14F5N5O2+H]+; HPLC (Method 2) 95.0% (AUC) tR=13.78 min.

Aufarbeitung

  1. temperatureheated
  2. temperatureat reflux temperature for 1.25 h
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue is purified by flash chromatography (silica, 95:5:0.5 methylene chloride/methanol/concentrated ammonium hydroxide as eluent)
  5. customto afford a viscous oil
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-d1ff1d8d088e480eb1f191129379c76a
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07700602B2

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