Dimethylformamide → 6-[1-(Difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-9-carbonitrile

HRID 1399369Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1399369
Br[C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([CH3:24])=[N:17][C:18]([O:22][CH3:23])=[N:19][C:20]=4[CH3:21])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:25]([O:30][CH:31]([F:33])[F:32])[C:26]([F:29])([F:28])[F:27])=[CH:4][CH:3]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:55][N:56](C)C=O>C(=O)([O-])O.[Na+].[C-]#N.[Zn+2].[C-]#N.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]>[F:33][CH:31]([F:32])[O:30][CH:25]([C:5]1[C:6]2[N:7]3[CH2:14][CH2:13][CH2:12][N:11]([C:15]4[C:20]([CH3:21])=[N:19][C:18]([O:22][CH3:23])=[N:17][C:16]=4[CH3:24])[C:8]3=[N:9][C:10]=2[C:2]([C:55]#[N:56])=[CH:3][CH:4]=1)[C:26]([F:28])([F:27])[F:29]

Komponenten

7

Edukt 3

HCID 6228DimethylformamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 577860939-Bromo-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

Produkt 1

HCID 577858226-[1-(Difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-9-carbonitrileAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 9-bromo-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (254 mg, 0.474 mmol), zinc cyanide (557 mg, 4.74 mmol), 2-(di-tert-butylphosphino)biphenyl (14.1 mg, 0.0474 mmol), and tris(dibenzylideneacetone)dipalladium (43.4 mg, 0.0474 mmol) in N,N-dimethylformamide (2.4 ml) was stirred at 120° C. under nitrogen for 7 hr. The mixture was diluted with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 75-100% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound as colorless crystals (118 mg, 0.245 mmol, 52%).

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel eluting with a 75-100% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give a solid, which
  9. customwas recrystallized from ethyl acetate/n-hexane

Quellen und Nachweise

ORD-Eintrag
ord-ee069489219548f7b2b2b3758113d038
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901141B2

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