Triethylamine → HCID 86751333, compound

HRID 1379216Notes

Reaction equation

HRID 1379216 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:26])[C:12]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=2)[C@H:7]([CH2:27][C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[NH:30][CH:29]=2)[CH2:6]1.[CH2:37]([N:39]([CH2:42]C)CC)C.[Cl:44]C(OC1C=CC([N+]([O-])=O)=CC=1)=[O:46]>O1CCCC1>[ClH:44].[F:24][C:22]([F:23])([F:25])[C:14]1[CH:13]=[C:12]([CH:17]=[C:16]([C:18]([F:20])([F:19])[F:21])[CH:15]=1)[C:11]([N:8]1[CH2:9][CH2:10][N:5]([CH2:4][CH2:3][CH2:2][NH:1][C:37]([NH:39][CH3:42])=[O:46])[CH2:6][C@H:7]1[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:26]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 86751335HCID 86751335, compound

Product 1

HCID 86751333HCID 86751333, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2R)-4-(3-aminopropyl)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-yl-methyl)piperazine (0.20 g) and triethylamine (0.06 ml) in tetrahydrofuran (10 ml) was added 4-nitrophenyl chloroformate (0.08 g) under ice-cooling. After 35 minutes, the resulting precipitate was filtered off. To the filtrate were added triethylamine (0.06 ml) and 30% methylamine in ethanol (0.05 ml) at room temperature. After stirring for 1 hour and 40 minutes, additional 30% methylamine in ethanol (0.05 ml) was added to the reaction mixture and then stirred for 45 minutes. The reaction mixture was concentrated in vacuo and the residue was partitioned between dichloromethane and water. The organic layer was separated, washed with aqueous saturated sodium chloride solution and dried over magnesium sulfate. After evaporation of the solvent in vacuo, the residue was purified by column chromatography on silica gel eluting with a mixed solvent of dichloromethane and methanol (100:3). The eluate was treated with 4N hydrogen chloride in dioxane solution to afford (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-yl-methyl)-4-[3-(3-methylureido)propyl]-piperazine hydrochloride (0.08 g).

Workup

  1. temperaturecooling
  2. filtrationthe resulting precipitate was filtered off
  3. additionTo the filtrate were added triethylamine (0.06 ml) and 30% methylamine in ethanol (0.05 ml) at room temperature
  4. additionadditional 30% methylamine in ethanol (0.05 ml) was added to the reaction mixture
  5. stirringstirred for 45 minutes
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. customthe residue was partitioned between dichloromethane and water
  8. customThe organic layer was separated
  9. washwashed with aqueous saturated sodium chloride solution
  10. dry with materialdried over magnesium sulfate
  11. customAfter evaporation of the solvent in vacuo
  12. customthe residue was purified by column chromatography on silica gel eluting with a mixed solvent of dichloromethane and methanol (100:3)
  13. additionThe eluate was treated with 4N hydrogen chloride in dioxane solution

Sources & evidence

ORD record
ord-b11b6c224a94415ebc5f4f3f42a73be9
Source dataset
uspto-grants-1997_09
Patent number
US05670505

Reaction notes

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