Water → (1-methyl-1H-indol-3-yl)(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-6-yl)methanone

HRID 2225616Notes

Reaction equation

HRID 2225616 reaction equation
Cl.[N:2]1[C:6]2[CH2:7][CH2:8][CH:9]([C:11](N3CCCC3)=[O:12])[CH2:10][C:5]=2[NH:4][CH:3]=1.[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20]1.P(Cl)(Cl)(Cl)=O.O>C(Cl)CCl>[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]([C:11]([CH:9]2[CH2:8][CH2:7][C:6]3[N:2]=[CH:3][NH:4][C:5]=3[CH2:10]2)=[O:12])=[CH:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 117811-MethylindoleHCID 24813Phosphorus oxychloride2×HCID 18985210Pyrrolidin-1-yl(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-5-yl)methanone hydrochloride

Product 1

HCID 4442(1-methyl-1H-indol-3-yl)(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-6-yl)methanoneYield 89.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

In a suspension of 7.0 g of N-[(4,5,6,7-tetrahydrobenzimidazol-5-yl)carbonyl]pyrrolidine hydrochloride and 5.4 g of N-methylindole in 70 ml of ethylene chloride was added 12.6 g of phosphorus oxychloride, and the mixture was stirred at 80° to 85° C. for 7 hours. After allowing the mixture to cool, the mixture was cooled to 0° to 5° C., and 70 ml of cold water was slowly added to the reaction mixture while maintaining the temperature of the mixture below room temperature to thereby decompose the excess of phosphorus oxychloride. The organic layer was removed, and the aqueous layer was adjusted to a pH of 9 with a 20% sodium hydroxide aqueous solution under cooling, followed by extracting from chloroform. To the chloroform layer was added 70 ml of water, and 6N hydrochloric acid was added thereto under ice-cooling while stirring to adjust to a pH of from 2.4 to 2.8. The chloroform layer was removed. The aqueous layer was washed with chloroform, and 40 ml of methanol was added thereto. The solution was made alkaline with a 20% sodium hydroxide aqueous solution while cooling. The formed crystal was collected by filtration and washed with a cold 1:1 (by volume) mixture of methanol and water to give 6.87 g (89.9%) of 5-[(1-methylindol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.

Workup

  1. temperatureto cool
  2. temperaturethe mixture was cooled to 0° to 5° C.
  3. temperaturewhile maintaining the temperature of the mixture below room temperature
  4. customThe organic layer was removed
  5. temperatureunder cooling
  6. extractionby extracting from chloroform
  7. additionTo the chloroform layer was added 70 ml of water, and 6N hydrochloric acid
  8. additionwas added
  9. temperatureunder ice-cooling
  10. stirringwhile stirring
  11. customThe chloroform layer was removed
  12. washThe aqueous layer was washed with chloroform, and 40 ml of methanol
  13. additionwas added
  14. temperaturewhile cooling
  15. filtrationThe formed crystal was collected by filtration
  16. washwashed with a cold 1:1 (by volume) mixture of methanol and water

Sources & evidence

ORD record
ord-7762bc16ed1b402db0bee19befc6c7fe
Source dataset
uspto-grants-1994_09
Patent number
US05344927

Reaction notes

Loading…