Methyl iodide → 9-Chloro-1-(2,4-dichlorophenyl)-6-(2,2,2-trifluoro-1-methoxyethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1628852Notes

Reaction equation

HRID 1628852 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([OH:28])[C:24]([F:27])([F:26])[F:25])=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:32]>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([O:28][CH3:32])[C:24]([F:25])([F:26])[F:27])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 577861691-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanol

Product 1

HCID 577862669-Chloro-1-(2,4-dichlorophenyl)-6-(2,2,2-trifluoro-1-methoxyethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 96.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanol (67.6 mg, 0.150 mmol) in tetrahydrofuran (1.0 mL) was added sodium hydride (60% in oil, 7.2 mg, 0.18 mmol) at 0° C. After 15 min, iodomethane (46.7 μL, 0.75 mmol) was added. After being stirred for 1.5 h at room temperature, the reaction mixture was diluted with ethyl acetate, washed with aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 0-50% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (67.2 mg, 0.145 mmol, 96%).

Workup

  1. washwashed with aqueous sodium hydrogen carbonate and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel eluting with a 0-50% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-d9177a33ccd24948b58755ff8f999ff7
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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