Tetrahydrofuran → 1-[1-(2,4-Dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-one

HRID 1399114Notes

Reaction equation

HRID 1399114 reaction equation
[CH2:1]([Mg]Br)[CH3:2].[Cl:5][C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[N:13]1[C:18]2=[N:19][C:20]3[C:21](=[C:22]([C:26]#N)[CH:23]=[CH:24][CH:25]=3)[N:17]2[CH2:16][CH2:15][CH2:14]1.[O:28]1CCCC1>>[Cl:5][C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[N:13]1[C:18]2=[N:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26](=[O:28])[CH2:1][CH3:2])[C:21]=3[N:17]2[CH2:16][CH2:15][CH2:14]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 577858151-(2,4-Dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbonitrileHCID 178418443HCID 178418443, compound

Product 1

HCID 577859441-[1-(2,4-Dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]propan-1-oneYield 56%

Conditions

Temperature
50 °C

Procedure

Ethylmagnesium bromide (3.0 M solution in diethyl ether, 14.6 mL, 43.7 mmol) was added to a stirred solution of 1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbonitrile (5.00 g, 14.6 mmol) in tetrahydrofuran (50 mL) at 0° C., and the mixture was stirred at 50° C. for 2 hr. The reaction was quenched by methanol, and 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. A mixture of the resulting imine, acetic acid (10 mL) and 1N hydrochloric acid (20 mL) was stirred at 50° C. for 2 hr. The mixture was concentrated in vacuo, diluted with saturated aqueous sodium hydrogen carbonate 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 recrystallized from ethyl acetate/diisopropyl ether to give the title compounds as a colorless crystal (3.04 g, 8.12 mmol, 56%).

Workup

  1. customThe reaction was quenched by methanol
  2. additionthe mixture was diluted with aqueous saturated ammonium chloride
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionA mixture of the resulting imine, acetic acid (10 mL) and 1N hydrochloric acid (20 mL)
  9. stirringwas stirred at 50° C. for 2 hr
  10. concentrationThe mixture was concentrated in vacuo
  11. additiondiluted with saturated aqueous sodium hydrogen carbonate
  12. extractionextracted with ethyl acetate
  13. washThe combined organic layer was washed with brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customThe residue was recrystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-b0bbdfc04f8f4dff8b6ad4f6ccebf68f
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

Loading…