Tetrahydrofuran → 4-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]heptan-4-ol

HRID 1628794Notes

Reaction equation

HRID 1628794 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:23]([O:25]C)=O)=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]21.[CH2:27]([Mg]Br)[CH2:28][CH3:29].O1C[CH2:35][CH2:34][CH2:33]1>>[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]([C:23]([OH:25])([CH2:33][CH2:34][CH3:35])[CH2:27][CH2:28][CH3:29])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 57785909Methyl 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylateHCID 178455851HCID 178455851, compound

Product 1

HCID 577861374-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]heptan-4-olYield 26%

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (200.0 mg, 0.487 mmol) in tetrahydrofuran (3.0 mL) was added n-propylmagnesium bromide (1.0 M solution in tetrahydrofuran, 2.44 mL, 2.435 mmol). The reaction mixture was stirred at 60° C. for 14 hrs. After cooling, the mixture was quenched with aqueous saturated ammonium chloride and extracted with ethyl acetate (×3). The combined organic layer was washed with brine, 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 hexane to give the title compound as a solid (60.0 mg, 0.129 mmol, 26%).

Workup

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

Sources & evidence

ORD record
ord-8bda7f6fe3854382842c720ccad6c59b
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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