Water → 5-[(2-Methylindolizin-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole

HRID 2225615Notes

Reaction equation

HRID 2225615 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][C:19]1[CH:20]=[C:21]2[N:26]([CH:27]=1)[CH:25]=[CH:24][CH:23]=[CH:22]2.P(Cl)(Cl)(Cl)=O.O>ClCCCl>[CH3:18][C:19]1[CH:20]=[C:21]2[N:26]([C:27]=1[C:11]([CH:9]1[CH2:8][CH2:7][C:6]3[N:2]=[CH:3][NH:4][C:5]=3[CH2:10]1)=[O:12])[CH:25]=[CH:24][CH:23]=[CH:22]2

Participants

6

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 5826302-MethylindolizineHCID 18985210Pyrrolidin-1-yl(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-5-yl)methanone hydrochloride

Product 1

HCID 189852225-[(2-Methylindolizin-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazoleYield 38.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 0.50 g of N-[(4,5,6,7-tetrahydrobenzimidazol-5-yl)carbonyl]pyrrolidinehydrochloride and 0.39 g of 2-methylindolizine in 5 ml of 1,2-dichloroethane was added dropwise 0.90 g of phosphorus oxychloride. The reaction mixture was refluxed at 85° C. for one night. After cooling to room temperature, 5 ml of water was added thereto. The organic layer was removed, and 10 ml of chloroform was added to the aqueous layer. The solution was adjusted to a pH of 9 with a 20% aqueous solution of sodium hydroxide and then extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation. The residue was purified by silica gel column chromatography using chloroform/methanol as an eluent, followed by recrystallization from ethanol to obtain 0.21 g of 5-[(2-methylindolizin-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole.

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe organic layer was removed
  3. addition10 ml of chloroform was added to the aqueous layer
  4. extractionextracted with chloroform
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. customthe solvent was removed by distillation
  7. customThe residue was purified by silica gel column chromatography
  8. customfollowed by recrystallization from ethanol

Sources & evidence

ORD record
ord-537106097f2848f4ba8749c2029b0f40
Source dataset
uspto-grants-1994_09
Patent number
US05344927

Reaction notes

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