4-Chloro-3-sulfamoylbenzoic acid → 3-(aminosulfonyl)-4-chloro-N-((1R)-1-(3-chlorophenyl)ethyl)benzamide

HRID 1801577Notes

Reaction equation

HRID 1801577 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([NH2:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[Cl:11][C:12]1[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][C:13]=1[S:21](=[O:24])(=[O:23])[NH2:22].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O.O>[NH2:22][S:21]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:12]=1[Cl:11])[C:16]([NH:10][C@@H:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[CH3:9])=[O:17])(=[O:24])=[O:23]

Participants

8

Reactant 4

HCID 145684-Chloro-3-sulfamoylbenzoic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2507697(R)-1-(3-chlorophenyl)ethanamine

Product 1

HCID 91647343-(aminosulfonyl)-4-chloro-N-((1R)-1-(3-chlorophenyl)ethyl)benzamideYield 89.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-1-(3-chlorophenyl)ethanamine (0.426 g, 2.74 mmol) and 4-chloro-3-sulfamoylbenzoic acid 37 (0.452 g, 1.92 mmol) in DMF (5 mL) at room temperature was added EDCI (0.439 g, 2.29 mmol) and HOBT (0.368 g, 2.40 mmol). The reaction mixture was stirred at room temperature for 16 h, and diluted with EtOAc and water. The organic phase was washed with water (2×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 50% to 80% EtOAc in hexanes) yielded 3-(aminosulfonyl)-4-chloro-N-((1R)-1-(3-chlorophenyl)ethyl)benzamide 38 (0.643 g, 89.8% yield) as a white solid. Mass spectrum: calculated for C15H14Cl2N2O3S 372.0. found 373.1 (M++1).

Workup

  1. washThe organic phase was washed with water (2×), brine (1×)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography on silica gel (eluted with 50% to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-bd2cf040e52e4e5498e9cf4fec8f18ba
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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