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

HRID 1399080Notes

Reaction equation

HRID 1399080 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]([CH3:29])([CH3:28])[CH2:26][OH:27])=[CH:6][CH:5]=1.[CH3:30]I>CN(C)C=O.[Cl-].[NH4+]>[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]([CH3:29])([CH3:28])[CH2:26][O:27][CH3:30])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 577858392-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2-methylpropan-1-ol

Product 1

HCID 577859339-Chloro-1-(2,4-dichlorophenyl)-6-(2-methoxy-1,1-dimethylethyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Sodium hydride (60% in oil, 10.2 mg, 0.255 mmol) was added to a stirred solution of 2-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2-methylpropan-1-ol (90.3 mg, 0.213 mmol) in N,N-dimethylformamide (2.0 mL) at room temperature. After stirring 5 min, methyl iodide (45.1 mg, 0.320 mmol) was added to the mixture, and the mixture was stirred at room temperature for 50 min. The mixture was diluted with aqueous saturated ammonium chloride, 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/diisopropyl ether to give the title compound as a colorless crystal (71.5 mg, 0.163 mmol, 77%).

Workup

  1. stirringthe mixture was stirred at room temperature for 50 min
  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/diisopropyl ether

Sources & evidence

ORD record
ord-6dd2f1fde3a5422e8f973e071af5bb76
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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