9-Chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole → 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 1399367Notes

Reaction equation

HRID 1399367 reaction equation
Cl[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(O)(=O)C.[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[CH:2]=[CH:3][CH:4]=1)[C:26]([F:29])([F:28])[F:27]

Participants

4

Reactant 1

HCID 441296849-Chloro-6-[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 577860406-[1-(Difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 70%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of 9-chloro-6-[1-(difluoromethoxy)-2,2,2-trifluoroethyl]-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (783 mg, 1.59 mmol) in acetic acid (8.0 mL) was added 10% palladium on carbon (50% wet, 78.3 mg), and the mixture was purged with hydrogen and stirred under balloon pressure hydrogen at room temperature for 2 days. The catalyst was removed by filtration, and the filtrate was concentrated in vacuo. The residue 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 washed with ethyl acetate/diisopropyl ether to give the title compound as a colorless powder (507 mg, 1.11 mmol, 70%)

Workup

  1. customthe mixture was purged with hydrogen
  2. customThe catalyst was removed by filtration
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionThe residue was diluted with saturated aqueous sodium hydrogen carbonate
  5. extractionextracted with ethyl acetate
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash column chromatography on silica gel eluting with a 75-100% ethyl acetate/n-hexane gradient mixture
  11. concentrationThe filtrate was concentrated in vacuo
  12. customto give a solid, which
  13. washwas washed with ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-329f8f365de14c909d926a99e613e4cd
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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