Sodium hydride → 9-Chloro-6-[1-(cyclopropylmethoxy)propyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1399148Notes

Reaction equation

HRID 1399148 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:26])[CH2:24][CH3:25])=[CH:4][CH:3]=1.[H-].[Na+].[CH:29]1([CH2:32]Br)[CH2:31][CH2:30]1>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:26][CH2:32][CH:29]2[CH2:31][CH2:30]2)[CH2:24][CH3:25])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 44156374HCID 44156374, compound

Product 1

HCID 577859969-Chloro-6-[1-(cyclopropylmethoxy)propyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoleYield 91%

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]propan-1-ol (120.0 mg, 0.292 mmol) in N,N-dimethylformamide (1.5 mL) was added sodium hydride (23.4 mg, 0.584 mmol) at 0° C. After 20 min, to the mixture was added cyclopropylmethyl bromide (0.14 mL, 1.46 mmol). The reaction mixture was stirred at room temperature for 1 day. 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 0-30% ethyl acetate/n-hexane gradient mixture. The resulting solid was recrystallized from n-hexane to give the title compound as a colorless powder (123.0 mg, 0.265 mmol, 91%).

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 0-30% ethyl acetate/n-hexane gradient mixture
  9. customThe resulting solid was recrystallized from n-hexane

Sources & evidence

ORD record
ord-673f550c1b134335b999566a2dbbdb3f
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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