Phosgene → 4-(4-Acryloylamino-benzenesulfonyl)-piperazine-1-carboxylic acid 2-chloro-benzyl ester

HRID 1841924Notes

Reaction equation

HRID 1841924 reaction equation
[C:1](Cl)(Cl)=[O:2].[Cl:5][C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[CH2:8][OH:9].[N:14]1([S:20]([C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C>C1COCC1.CN(C=O)C>[Cl:5][C:6]1[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=1[CH2:8][O:9][C:1]([N:17]1[CH2:16][CH2:15][N:14]([S:20]([C:23]2[CH:24]=[CH:25][C:26]([NH:29][C:30](=[O:33])[CH:31]=[CH2:32])=[CH:27][CH:28]=2)(=[O:21])=[O:22])[CH2:19][CH2:18]1)=[O:2]

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 288102-Chlorobenzyl alcoholHCID 81531DiisopropylethylamineHCID 56953730N-[4-(piperazine-1-sulfonyl)-phenyl]-acrylamide

Product 1

HCID 529396444-(4-Acryloylamino-benzenesulfonyl)-piperazine-1-carboxylic acid 2-chloro-benzyl esterYield 12%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

Phosgene (0.5 ml, 20% solution in toluene) was added in one portion to a stirred solution of 2-chlorobenzyl alcohol (0.1 g, 0.7 mmol) in THF (2 ml) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. After this time the reaction mixture was concentrated under vacuum and the resulting residue was diluted with DMF (2 ml) and added drop wise to a stirred solution of N-[4-(piperazine-1-sulfonyl)-phenyl]-acrylamide (0.16 g, 0.54 mmol) and diisopropylethylamine (0.19 ml, 1.1 mmol) in DMF (4 ml). The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours. After this time the reaction mixture was concentrated under vacuum and the residue was purified by Prep HPLC to give the title compound (0.029 g, 12% yield) as a white powder.

Workup

  1. concentrationAfter this time the reaction mixture was concentrated under vacuum
  2. additionthe resulting residue was diluted with DMF (2 ml)
  3. stirringThe resulting mixture was stirred at room temperature under a nitrogen atmosphere for 18 hours
  4. concentrationAfter this time the reaction mixture was concentrated under vacuum
  5. customthe residue was purified by Prep HPLC

Sources & evidence

ORD record
ord-852b23af1f314c938a12cbf4ce4c30bc
Source dataset
uspto-grants-2015_02
Patent number
US08946197B2

Reaction notes

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