1-Hydroxybenzotriazole → (S)-3-(4-Benzyloxybenzenesulfonylamino)-N-hydroxy-2-(4-methanesulfonyl-piperazin-1-yl)propionamide

HRID 874564Notes

Reaction equation

HRID 874564 reaction equation
[OH:1][N:2]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34]([S:37]([NH:40][CH2:41][C@H:42]([N:46]2[CH2:51][CH2:50][N:49]([S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:47]2)[C:43](O)=[O:44])(=[O:39])=[O:38])=[CH:33][CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Si](ON)(C(C)(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[CH2:23]([O:30][C:31]1[CH:32]=[CH:33][C:34]([S:37]([NH:40][CH2:41][C@H:42]([N:46]2[CH2:51][CH2:50][N:49]([S:52]([CH3:55])(=[O:54])=[O:53])[CH2:48][CH2:47]2)[C:43]([NH:2][OH:1])=[O:44])(=[O:38])=[O:39])=[CH:35][CH:36]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

9

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 66870630(S)-3-(4-benzyloxybenzenesulfonylamino)-2-(4-methanesulfonylpiperazin-1-yl)propanoic acid

Product 1

HCID 49849090(S)-3-(4-Benzyloxybenzenesulfonylamino)-N-hydroxy-2-(4-methanesulfonyl-piperazin-1-yl)propionamideYield 39%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

224 mg (1.7 mmol) of 1-hydroxybenzotriazole and 318 mg (1.7 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride are added successively to 750 mg (1.5 mmol) of (S)-3-(4-benzyloxybenzenesulfonylamino)-2-(4-methanesulfonylpiperazin-1-yl)propanoic acid in 20 ml of dimethylformamide. After stirring at ambient temperature for 20 min, a solution of 244 mg (1.7 mmol) of O-tert-butyldimethylsilylhydroxylamine in 3 ml of dimethylformamide is added. The reaction medium is then stirred at ambient temperature for 18 h and then 2 ml of a saturated aqueous solution of sodium hydrogen carbonate and finally 2 ml of water are added. After extraction with ethyl acetate, the organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated. The crude residue obtained is taken up in 15 ml of ethyl acetate, heated to 70° C. and then brought back to ambient temperature, filtered and dried under vacuum. 300 mg (34%) of (S)-3-(4-benzyloxybenzenesulfonylamino)-N-hydroxy-2-(4-methanesulfonylpiperazin-1-yl)propionamide are obtained in the form of a white solid having a melting point of 165° C.

Workup

  1. stirringThe reaction medium is then stirred at ambient temperature for 18 h
  2. extractionAfter extraction with ethyl acetate
  3. washthe organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue obtained
  8. temperatureheated to 70° C.
  9. custombrought back to ambient temperature
  10. filtrationfiltered
  11. customdried under vacuum

Sources & evidence

ORD record
ord-703b7922e68e45ba9799dc7a8952bda9
Source dataset
uspto-grants-2015_03
Patent number
US08980897B2

Reaction notes

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