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

HRID 1399047Notes

Reaction equation

HRID 1399047 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]([OH:30])([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:6][CH:5]=1.[CH3:31]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]([CH2:28][CH3:29])([O:30][CH3:31])[CH2:26][CH3:27])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 577863903-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentan-3-ol

Product 1

HCID 577859869-Chloro-1-(2,4-dichlorophenyl)-6-(1-ethyl-1-methoxypropyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 84.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Sodium hydride (60% in oil, 21.8 mg, 0.546 mmol) was added to a stirred solution of 3-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]pentan-3-ol (200 mg, 0.456 mmol) in N,N-dimethylformamide (2.0 mL) at room temperature. After stirring 5 min, methyl iodide (97.0 mg, 0.684 mmol) was added to the mixture, and the mixture was stirred at room temperature for 5 hr. 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 10-50% 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 (174 mg, 0.384 mmol, 84%).

Workup

  1. stirringthe mixture was stirred at room temperature for 5 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 10-50% 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-68d685cf832e4e9981f9abe9debb746d
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

Loading…