1-Hydroxybenzotriazole → HCID 18391354, compound

HRID 1585548Notes

Reaction equation

HRID 1585548 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[C:6]([N:8]1[C@H:13]([CH2:14][C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:12][N:11]([CH2:24][C:25]([OH:27])=O)[C:10](=[O:28])[CH2:9]1)=[O:7].[CH3:38][N:39]1[CH2:45][CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.ON1C2C=CC=CC=2N=N1.[ClH:56].CN(C)CCCN=C=NCC.C(=O)(O)[O-].[Na+]>ClCCl.O>[ClH:56].[F:1][C:2]([F:36])([F:37])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=1)[C:6]([N:8]1[C@H:13]([CH2:14][C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)[CH2:12][N:11]([CH2:24][C:25]([N:42]2[CH2:43][CH2:44][CH2:45][N:39]([CH3:38])[CH2:40][CH2:41]2)=[O:27])[C:10](=[O:28])[CH2:9]1)=[O:7]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 2283491-MethylhomopiperazineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54494969HCID 54494969, compound

Product 1

HCID 18391354HCID 18391354, compoundYield 70.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice-cooled solution of (5R)-4-[3,5-bis(trifluoromethyl)benzoyl]-1-(carboxymethyl)-5-(1H-indol-3-ylmethyl)piperazin-2-one (0.15 g), 1-methylhomopiperazine (0.032 g) and 1-hydroxybenzotriazole (0.038 g) in dichloromethane (3 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.055 g). The mixture was stirred at the same temperature for 1 hour and then at room temperature for 16 hours. Water and aqueous sodium bicarbonate solution were added and then the resulting mixture was extracted with dichloromethane. The organic layer was washed successively with aqueous sodium bicarbonate solution, water and brine, and dried over magnesium sulfate. After evaporation in vacuo, the residue (0.13 g) was dissolved in dichloromethane (2 ml). To the solution was added 4N hydrogen chloride in dioxane solution (0.052 ml) under ice-cooling, and the mixture was stirred for 50 minutes at the same temperature. After concentration, ether was added to the residue and the resulting precipitates were collected by filtration, washed with ether, and dried to give (5R)-4-[3,5-bis(trifluoromethyl)benzoyl]-5-(1H-indol-3-ylmethyl)-1-[(4-methyl-1-homopiperazinyl)carbonylmethyl]-piperazin-2-one hydrochloride (0.13 g) as an amorphous solid.

Workup

  1. waitat room temperature for 16 hours
  2. extractionthe resulting mixture was extracted with dichloromethane
  3. washThe organic layer was washed successively with aqueous sodium bicarbonate solution, water and brine
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation in vacuo
  6. dissolutionthe residue (0.13 g) was dissolved in dichloromethane (2 ml)
  7. additionTo the solution was added 4N hydrogen chloride in dioxane solution (0.052 ml) under ice-
  8. temperaturecooling
  9. stirringthe mixture was stirred for 50 minutes at the same temperature
  10. concentrationAfter concentration, ether
  11. additionwas added to the residue
  12. customthe resulting precipitates
  13. filtrationwere collected by filtration
  14. washwashed with ether
  15. customdried

Sources & evidence

ORD record
ord-dfaf7614d0514fa3b222d194dc09dabe
Source dataset
uspto-grants-1999_08
Patent number
US05939413

Reaction notes

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