N-bromobutanimide → 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

HRID 1629016Notes

Reaction equation

HRID 1629016 reaction equation
[Br:1]N1C(=O)CCC1=O.[F:9][CH:10]([F:40])[O:11][CH:12]([C:17]1[C:22]2[N:23]3[CH2:29][CH2:28][CH2:27][N:26]([C:30]4[C:31]([CH3:39])=[N:32][C:33]([O:37][CH3:38])=[N:34][C:35]=4[CH3:36])[C:24]3=[N:25][C:21]=2[CH:20]=[CH:19][CH:18]=1)[C:13]([F:16])([F:15])[F:14]>C(#N)C.C(=O)([O-])O.[Na+]>[Br:1][C:20]1[C:21]2[N:25]=[C:24]3[N:26]([C:30]4[C:35]([CH3:36])=[N:34][C:33]([O:37][CH3:38])=[N:32][C:31]=4[CH3:39])[CH2:27][CH2:28][CH2:29][N:23]3[C:22]=2[C:17]([CH:12]([O:11][CH:10]([F:9])[F:40])[C:13]([F:16])([F:15])[F:14])=[CH:18][CH:19]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 577860406-[1-(Difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

Product 1

HCID 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]benzimidazoleYield 60.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

N-Bromosuccinimide (190 mg, 1.07 mmol) was added to a stirred solution of 6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (469 mg, 1.02 mmol) in acetonitrile (5.0 mL) at room temperature, and the mixture was stirred at room temperature for 5 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 70-100% 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 (330 mg, 0.615 mmol, 60%).

Workup

  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 70-100% 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

Sources & evidence

ORD record
ord-2cd5942eb35d4863b7aaa8652c78dd9c
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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