Hydrochloric Acid → N-(3,4-Dimethyl-5-isoxazolyl)-2-[1-(phenylsulfonyl)-1H-indol-3-yl]benzenesulfonamide

HRID 1585671Notes

Reaction equation

HRID 1585671 reaction equation
[CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([N:8](COCCOC)[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:29])=[O:28])[CH:19]=2)(=[O:11])=[O:10])[O:4][N:3]=1.Cl.CCO>CO.O>[CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([S:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)(=[O:28])=[O:29])[CH:19]=2)(=[O:10])=[O:11])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 21219232N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-2-[1-(phenylsulfonyl)-1H-indol-3-yl]benzenesulfonamide

Product 1

HCID 9849124N-(3,4-Dimethyl-5-isoxazolyl)-2-[1-(phenylsulfonyl)-1H-indol-3-yl]benzenesulfonamideYield 43.4%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A mixture of the title product of Step (D) (350 mg; 0.59 mmol), 6N HCl (6 ml) and EtOH (6 ml) was refluxed for 3 hours. After cooling, the reaction mixture was partitioned between EtOAc (50 ml) and water (25 ml). The aqueous layer was extracted with EtOAc (50 ml) and the combined organic layers were washed with brine (2×50 ml). The blue solution was dried (MgSO4) and concentrated to a dark blue residue. Attempts at purifying this residue using silica gel chromatography were unsuccessful. The material isolated from combining all fractions was subjected to reverse phase preparative HPLC. (30×500 mm ODS column; S-3; two injections-30 and 150 mg; stepwise gradient 75-83% MeOH/H2O+0.1% trifluoroacetic acid (TFA); 2% increments every 5 minutes; 35 ml/minute flow rate.) The pure fractions were concentrated and the residues were partitioned between EtOAc and water. The organic layer was washed with water and brine. Drying (MgSO4), concentration and co-evaporation from MeOH/H2O afforded 130 mg (43%) of the title product of this Example as a light yellow amorphous solid. mp 85-95° C. (dec.); Rf=0.63, EtOAc (UV detection).

Workup

  1. temperaturewas refluxed for 3 hours
  2. temperatureAfter cooling
  3. customthe reaction mixture was partitioned between EtOAc (50 ml) and water (25 ml)
  4. extractionThe aqueous layer was extracted with EtOAc (50 ml)
  5. washthe combined organic layers were washed with brine (2×50 ml)
  6. dry with materialThe blue solution was dried (MgSO4)
  7. concentrationconcentrated to a dark blue residue
  8. customAttempts at purifying this residue
  9. customThe material isolated
  10. customevery 5 minutes
  11. concentration) The pure fractions were concentrated
  12. customthe residues were partitioned between EtOAc and water
  13. washThe organic layer was washed with water and brine
  14. customDrying
  15. concentration(MgSO4), concentration and co-evaporation from MeOH/H2O

Sources & evidence

ORD record
ord-32555357d7094107ae7c1291cd671461
Source dataset
uspto-grants-1999_08
Patent number
US05939446

Reaction notes

Loading…