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

HRID 1399054Notes

Reaction equation

HRID 1399054 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:12]2[N:11]=[C:10]3[N:13]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[CH2:14][CH2:15][CH2:16][N:9]3[C:8]=2[C:7]([CH:25]([OH:29])[CH2:26][CH2:27][CH3:28])=[CH:6][CH:5]=1.[CH3:30]I>CN(C)C=O.O>[Cl:3][C:4]1[C:12]2[N:11]=[C:10]3[N:13]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[CH2:14][CH2:15][CH2:16][N:9]3[C:8]=2[C:7]([CH:25]([O:29][CH3:30])[CH2:26][CH2:27][CH3:28])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 577861451-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]butan-1-ol

Product 1

HCID 577862329-Chloro-1-(2,4-dichlorophenyl)-6-(1-methoxybutyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 36%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 50.8 mg, 1.27 mmol) was added to a stirred solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]butan-1-ol (250 mg, 1.06 mmol) in N,N-dimethylformamide (3.0 mL) at room temperature. After stirring 5 min, methyl iodide (226 mg, 1.59 mmol) was added to the mixture, and the mixture was stirred at room temperature for 3 hr. The mixture was diluted with water, 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 5-50% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/diisopropyl ether to give the title compound as a colorless crystal (166 mg, 0.378 mmol, 36%).

Workup

  1. stirringthe mixture was stirred at room temperature for 3 hr
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel eluting with a 5-50% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give the solid, which
  10. customwas recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-40a512aec6da466abf61a2848387fa56
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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