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

HRID 1399048Notes

Reaction equation

HRID 1399048 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]([C:25]([CH:30]2[CH2:32][CH2:31]2)([CH:27]2[CH2:29][CH2:28]2)[OH:26])=[CH:6][CH:5]=1.[CH3:33]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]([C:25]([CH:30]2[CH2:32][CH2:31]2)([CH:27]2[CH2:29][CH2:28]2)[O:26][CH3:33])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57786360[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](dicyclopropyl)methanol

Product 1

HCID 577863949-Chloro-1-(2,4-dichlorophenyl)-6-[dicyclopropyl(methoxy)methyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 17.5 mg, 0.438 mmol) was added to a stirred solution of [9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl](dicyclopropyl)methanol (100 mg, 0.216 mmol) in N,N-dimethylformamide (1.0 mL) at room temperature. After stirring min, methyl iodide (61.3 mg, 0.422 mmol) was added to the mixture, and the mixture was stirred at room temperature for 6 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 10-40% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (59.4 mg, 0.125 mmol, 58%).

Workup

  1. additionwas added to the mixture
  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 10-40% 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/n-hexane

Sources & evidence

ORD record
ord-ed712864dc824d5a98c4e47e3c2175ed
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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