1-Hydroxybenzotriazole → N-[[2-[3-(2-benzothiazolylmethoxy)benzoylamino]-4-[3-(4-chlorophenylsulfonyl)propyl]phenoxy]acetyl]glycine amide

HRID 1602513Notes

Reaction equation

HRID 1602513 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:42]=[CH:43][CH:44]=1)[C:15]([NH:17][C:18]1[CH:28]=[C:27]([CH2:29][CH2:30][CH2:31][S:32]([C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=2)(=[O:34])=[O:33])[CH:26]=[CH:25][C:19]=1[O:20][CH2:21][C:22]([OH:24])=O)=[O:16].Cl.[NH2:46][CH2:47][C:48]([NH2:50])=[O:49].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>C(OCC)(=O)C.O.CN(C)C=O.C(N(CC)CC)C>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][O:11][C:12]1[CH:13]=[C:14]([CH:42]=[CH:43][CH:44]=1)[C:15]([NH:17][C:18]1[CH:28]=[C:27]([CH2:29][CH2:30][CH2:31][S:32]([C:35]2[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=2)(=[O:33])=[O:34])[CH:26]=[CH:25][C:19]=1[O:20][CH2:21][C:22]([NH:50][C:48](=[O:49])[CH2:47][NH2:46])=[O:24])=[O:16]

Participants

9

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 2723639Glycinamide hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 542101982-[3-(2-Benzothiazolylmethoxy)benzoylamino]-4-[3-(4-chlorophenylsulfonyl)propyl]phenoxyacetic acid

Product 1

HCID 86754776N-[[2-[3-(2-benzothiazolylmethoxy)benzoylamino]-4-[3-(4-chlorophenylsulfonyl)propyl]phenoxy]acetyl]glycine amideYield 39%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under ice-cooling, triethylamine (220 μl) was added to a mixture of 2-[3-(2-benzothiazolylmethoxy)benzoylamino]-4-[3-(4-chlorophenylsulfonyl)propyl]phenoxyacetic acid (400 mg, 0.62 mmol), glycine amide hydrochloride (86 mg), 1-hydroxybenzotriazole (125 mg), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (130 mg) and N,N-dimethylformamide (10 ml), and the mixture prepared was stirred at room temperature for 12 hours. Water and ethyl acetate were added to the reaction solution. The insoluble solid material formed was collected by filtration, washed with ethyl acetate, water, 1 N hydrochloric acid, water, ether, 1 N sodium hydroxide aqueous solution, water and ether in that order and then dried under reduced pressure. Acetonitrile (13 ml) was added to the resulting solid material, and the mixture was heated under reflux for 5 minutes with stirring and then cooled. The crystals formed were collected by filtration to give N-[[2-[3-(2-benzothiazolylmethoxy)benzoylamino]-4-[3-(4-chlorophenylsulfonyl)propyl]phenoxy]acetyl]glycine amide (170 mg, 0.24 mmol, 39%) as colorless crystals.

Workup

  1. temperatureUnder ice-cooling
  2. customthe mixture prepared
  3. customThe insoluble solid material formed
  4. filtrationwas collected by filtration
  5. washwashed with ethyl acetate, water, 1 N hydrochloric acid, water, ether, 1 N sodium hydroxide aqueous solution, water and ether in that order
  6. customdried under reduced pressure
  7. additionAcetonitrile (13 ml) was added to the resulting solid material
  8. temperaturethe mixture was heated
  9. temperatureunder reflux for 5 minutes
  10. stirringwith stirring
  11. temperaturecooled
  12. customThe crystals formed
  13. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-3a964f856fa94049a532437515ceb02e
Source dataset
uspto-grants-1999_11
Patent number
US05981559

Reaction notes

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