Ammonia → HCID 86754413, compound

HRID 1585547Notes

Reaction equation

HRID 1585547 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](O)=[O:26])[C:10](=[O:28])[CH2:9]1)=[O:7].O[N:39]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.N>ClCCl>[F:34][C:32]([F:33])([F:35])[C:30]1[CH:29]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:36])[F:37])[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](=[O:26])[NH2:39])[C:10](=[O:28])[CH2:9]1)=[O:7]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 54494969HCID 54494969, compound

Product 1

HCID 86754413HCID 86754413, compoundYield 67.5%

Reagents, catalysts & solvents 1

HCID 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) and 1-hydroxybenzotriazole (0.038 g) in dichloromethane (3 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.055 g). After the solution was stirred for 2 hours and 55 minutes at the same temperature, 28% aqueous ammonia solution (0.017 ml) was added into the mixture under ice-cooling. The mixture was stirred for 2 hours and 25 minutes at room temperature. After evaporation of the solvent, the residue was extracted with ethyl acetate. 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 was purified by column chromatography on silica gel (10 g) eluting with a mixture of dichloromethane-methanol (from 0c to 5% gradient solution). To the eluate containing objective product was added diisopropyl ether and the resulting precipitates were collected by filtration, washed with diisopropyl ether, and dried to give (5R)-4-[3,5-bis(trifluoromethyl)benzoyl]-1-(carbamoylmethyl)-5-(1H-indol-3-ylmethyl)piperazin-2-one (0.10 g) as an amorphous solid.

Workup

  1. additionwas added into the mixture under ice-
  2. temperaturecooling
  3. customAfter evaporation of the solvent
  4. extractionthe residue was extracted with ethyl acetate
  5. washThe organic layer was washed successively with aqueous sodium bicarbonate solution, water and brine
  6. dry with materialdried over magnesium sulfate
  7. customAfter evaporation in vacuo
  8. customthe residue was purified by column chromatography on silica gel (10 g)
  9. washeluting with a mixture of dichloromethane-methanol (from 0c to 5% gradient solution)
  10. additionTo the eluate containing objective product was added diisopropyl ether
  11. customthe resulting precipitates
  12. filtrationwere collected by filtration
  13. washwashed with diisopropyl ether
  14. customdried

Sources & evidence

ORD record
ord-b4dc28cfa64a45de8486d070918955c6
Source dataset
uspto-grants-1999_08
Patent number
US05939413

Reaction notes

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