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

HRID 1399147Notes

Reaction equation

HRID 1399147 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:27])[CH:24]([CH3:26])[CH3:25])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:30]I>CN(C)C=O>[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:27][CH3:30])[CH:24]([CH3:25])[CH3:26])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 577863881-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2-methylpropan-1-ol

Product 1

HCID 577857819-Chloro-1-(2,4-dichlorophenyl)-6-(1-methoxy-2-methylpropyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2-methylpropan-1-ol (73.6 mg, 0.173 mmol) in N,N-dimethylformamide (1.0 mL) was added sodium hydride (10.3 mg, 0.260 mmol) at 0° C. After 30 min, to the mixture was added methyl iodide (53.9 μL, 0.865 mmol) at 0° C. The reaction mixture was stirred at room temperature for 12 hrs. The mixture was quenched with water and extracted with ethyl acetate (×3). The combined organic layer was washed with water (×2) and brine (×1), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 0-50% ethyl acetate/n-hexane gradient mixture. The resulting solid was recrystallized from n-hexane to give the title compound as a colorless powder (43.7 mg, 0.0996 mmol, 58%).

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined organic layer was washed with water (×2) and brine (×1)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with a 0-50% ethyl acetate/n-hexane gradient mixture
  9. customThe resulting solid was recrystallized from n-hexane

Sources & evidence

ORD record
ord-f7e5c65e190e4e80bcc21835c3588854
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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