Triethylamine → 3,5-Dichloro-N-(3-(N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)sulfamoyl)benzyl)-N-(4-fluorobenzyl)-2-hydroxybenzenesulfonamide

HRID 1889658Notes

Reaction equation

HRID 1889658 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:34]=[C:35]([Cl:37])[CH:36]=1)[CH2:5][N:6]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[S:7]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][NH:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[CH:11]=1)(=[O:9])=[O:8].[Cl:38][C:39]1[C:40]([OH:50])=[C:41]([S:46](Cl)(=[O:48])=[O:47])[CH:42]=[C:43]([Cl:45])[CH:44]=1.CCN(CC)CC.S(Cl)(Cl)(=O)=O>C1COCC1>[Cl:38][C:39]1[C:40]([OH:50])=[C:41]([S:46]([N:17]([CH2:16][C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([S:7](=[O:8])(=[O:9])[N:6]([CH2:5][C:4]3[CH:3]=[C:2]([Cl:1])[CH:36]=[C:35]([Cl:37])[CH:34]=3)[CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH:11]=2)[CH2:18][C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)(=[O:48])=[O:47])[CH:42]=[C:43]([Cl:45])[CH:44]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 24648Sulfuryl chlorideHCID 900783,5-Dichloro-2-hydroxybenzenesulphonyl chlorideHCID 58531573N-(3,5-Dichlorobenzyl)-N-(4-fluorobenzyl)-3-((4-fluorobenzylamino)methyl)benzenesulfonamide

Product 1

HCID 585314823,5-Dichloro-N-(3-(N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)sulfamoyl)benzyl)-N-(4-fluorobenzyl)-2-hydroxybenzenesulfonamideYield 54.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)-3-((4-fluorobenzylamino)methyl)benzenesulfonamide (75 mg, 0.13 mmol) in THF (4 mL) at rt was added 3,5-dichloro-2-hydroxybenzene-1-sulfonyl chloride (38 mg, 0.15 mmol) and Et3N (0.06 mL, 0.40 mmol) and it was stirred at rt for 1.5 h. Additional sulfonyl chloride (15 mg) and Et3N (0.05 mL) were added to the reaction mixture, and it was continued to stir for 2 h. The mixture was concentrated and the residue was purified by preparative HPLC (Condition: solvent A: 10% MeOH-90% H2O-0.1% TFA; Solvent B: 90% MeOH-10% H2O-0.1% TFA. Column 3: YMC S5 ODS 20×100 mm; 45% B to final 100% B, gradient time: 10 minutes, flow rate: 20 ml/min) to give the desired product as a white solid (56 mg, 53%). 1H NMR (CD3OD): δ 7.72 (d, J=7.2 Hz, 1H), 7.70 (d, J=2.8 Hz, 1H), 7.64 (s, 1H), 7.58 (d, J=2.8 Hz, 1H), 7.50-7.46 (m, 2H), 7.20-7.10 (m, 5H), 6.93-6.90 (m, 6H), 4.61 (s, 2H), 4.46 (s, 2H), 4.26 (s, 2H), 4.21 (s, 21-1); MS (ESI): [M−H]−=784.9.

Workup

  1. stirringto stir for 2 h
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by preparative HPLC (Condition

Sources & evidence

ORD record
ord-2792361cb4814a2a9d84c251efe95463
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

Loading…