Phosgene → N-{4-[4-(Piperidine-1-carbonyl)-piperazine-1-sulfonyl]-phenyl}-acrylamide

HRID 1841926Notes

Reaction equation

HRID 1841926 reaction equation
[C:1](Cl)(Cl)=[O:2].[NH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.[N:11]1([S:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:30])[CH:28]=[CH2:29])=[CH:22][CH:21]=2)(=[O:19])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(C(C)C)CC)(C)C>C1COCC1.CN(C=O)C>[N:5]1([C:1]([N:14]2[CH2:13][CH2:12][N:11]([S:17]([C:20]3[CH:21]=[CH:22][C:23]([NH:26][C:27](=[O:30])[CH:28]=[CH2:29])=[CH:24][CH:25]=3)(=[O:18])=[O:19])[CH2:16][CH2:15]2)=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 56953730N-[4-(piperazine-1-sulfonyl)-phenyl]-acrylamide

Product 1

HCID 52938046N-{4-[4-(Piperidine-1-carbonyl)-piperazine-1-sulfonyl]-phenyl}-acrylamideYield 14%

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 piperidine (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 (0.032 g, 14% 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-0d5a1e71be314f479af632b7ae1553dc
Source dataset
uspto-grants-2015_02
Patent number
US08946197B2

Reaction notes

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