Phosphorus oxychloride → 5-[(3-Methylindolizin-1-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole

HRID 2225621Notes

Reaction equation

HRID 2225621 reaction equation
Cl.N1([C:7]([CH:9]2[CH2:17][CH2:16][C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH2:10]2)=[O:8])CCCC1.P(Cl)(Cl)(Cl)=O.[CH3:23][C:24]1[N:32]2[C:27]([CH:28]=[CH:29][CH:30]=[CH:31]2)=[CH:26][CH:25]=1>ClC(Cl)C>[CH3:23][C:24]1[N:32]2[C:27]([CH:28]=[CH:29][CH:30]=[CH:31]2)=[C:26]([C:7]([CH:9]2[CH2:17][CH2:16][C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH2:10]2)=[O:8])[CH:25]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 5826233-MethylindolizineHCID 18985210Pyrrolidin-1-yl(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-5-yl)methanone hydrochloride

Product 1

HCID 1837815-[(3-Methylindolizin-1-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazoleYield 84.8%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To 10 ml of dichloroethane were added 1.08 g of 5-pyrrolidinocarbonyl-4,5,6,7-tetrahydrobenzimidazole hydrochloride and 1.18 ml of phosphorus oxychloride, and the mixture was stirred at 80° C. for 1 hour. At the same temperature 0.69 g of 3-methylindolizine in 2 ml of dichloroethane was added dropwise thereto during 15 minutes. The mixture was refluxed while stirring for 3 hours after that the mixture was poured into 20 ml of ice-water, and then the mixture was stirred at room temperature for 30 minutes. After liquid-liquid separation, the aqueous layer was washed with 10 ml of dichloromethane. Further, the aqueous layer was adjusted to a pH of about 9 with an aqueous 20% sodium hydroxide solution and then extracted with 20 ml of chloroform-methanol (4:1) twice. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed off under reduced pressure. The residue was washed with 20 ml of dichloromethane-ethylacetate (3:1) to obtain 1.00 g of 5-[(3-methylindolizin-1-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.

Workup

  1. waitduring 15 minutes
  2. temperatureThe mixture was refluxed
  3. stirringwhile stirring for 3 hours after that the mixture
  4. stirringthe mixture was stirred at room temperature for 30 minutes
  5. customAfter liquid-liquid separation
  6. washthe aqueous layer was washed with 10 ml of dichloromethane
  7. extractionextracted with 20 ml of chloroform-methanol (4:1) twice
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. customthe solvent was removed off under reduced pressure
  10. washThe residue was washed with 20 ml of dichloromethane-ethylacetate (3:1)

Sources & evidence

ORD record
ord-148e7e1763eb4a21829a93bfdc7add99
Source dataset
uspto-grants-1994_09
Patent number
US05344927

Reaction notes

Loading…