Dichloromethane → HCID 86751325, compound

HRID 1379212Notes

Reaction equation

HRID 1379212 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7].[C:33]([N:40]1[CH:44]=[CH:43]N=[CH:41]1)(N1C=CN=C1)=[O:34].Cl[CH2:46]Cl>>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:24]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:31])[F:32])[CH:26]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:33](=[O:34])[N:40]([CH3:41])[CH2:44][CH2:43][CH3:46])[CH2:10][C@H:9]1[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:7]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 682631,1'-Carbonyldiimidazole2×HCID 10972505(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazine

Product 1

HCID 86751325HCID 86751325, compound

Procedure

To a stirred solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-yl-methyl)piperazine (400 mg) in dichloromethane (5 ml) was added 1,1'-carbonyldiimidazole (140 mg) at room temperature. The resulting mixture was stirred overnight. Additional 1,1'-carbonyldiimidazole (70 mg) was added to the mixture and then stirred for 1 hour. After the dichloromethane was removed under reduced pressure, N-methylpropylamine (1 g) was added. The mixture was stirred at room temperature for 2 hours and then at reflux temperature for 12 hours. After cooling, dichloromethane and water were added to the reaction mixture. The organic layer was separated, washed with aqueous 0.5N hydrochloric acid and brine. After evaporation of the solvent, the residue was purified by column chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (99:1) to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-yl-methyl)-4-(N-methyl-N-propylcarbamoyl)piperazine (0.18 g).

Workup

  1. stirringstirred for 1 hour
  2. customAfter the dichloromethane was removed under reduced pressure, N-methylpropylamine (1 g)
  3. additionwas added
  4. stirringThe mixture was stirred at room temperature for 2 hours
  5. temperatureat reflux temperature for 12 hours
  6. temperatureAfter cooling
  7. additiondichloromethane and water were added to the reaction mixture
  8. customThe organic layer was separated
  9. washwashed with aqueous 0.5N hydrochloric acid and brine
  10. customAfter evaporation of the solvent
  11. customthe residue was purified by column chromatography on silica gel
  12. washeluting with a mixture of dichloromethane and methanol (99:1)

Sources & evidence

ORD record
ord-8cff7da25d334639be1d921dca980220
Source dataset
uspto-grants-1997_09
Patent number
US05670505

Reaction notes

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