Sodium Hydroxide → 4-((3-chlorophenyl)amino)-3-hydroxy-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide formate

HRID 528568Notes

Reaction equation

HRID 528568 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([S:17]([N:20](CC4C=CC(OC)=CC=4OC)[C:21]4[S:22][CH:23]=[N:24][N:25]=4)(=[O:19])=[O:18])=[CH:16][C:11]=3[O:10][C:9]2=[O:37])[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+].[NH4+].[Cl-]>CO>[CH:9]([OH:37])=[O:10].[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:12]2[CH:13]=[CH:14][C:15]([S:17]([NH:20][C:21]3[S:22][CH:23]=[N:24][N:25]=3)(=[O:18])=[O:19])=[CH:16][C:11]=2[OH:10])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 897613473-(3-chlorophenyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 897619394-((3-chlorophenyl)amino)-3-hydroxy-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide formate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A sealable vial was charged with 3-(3-chlorophenyl)-N-(2,4-dimethoxybenzyl)-2-oxo-N-(1,3,4-thiadiazol-2-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (38 mg, 0.068 mmol), and an aqueous solution of sodium hydroxide (2549 μL, 5.10 mmol) was added. The mixture was heated at 80° C. for 1 h, then poured into sat. aq. NH4Cl. The solution became heterogeneous, extracted with DCM, product did not go into organic layer, even after addition of brine. Aqueous layer was lyophilized to give product along with salts. The mixture was dissolved in MeOH and filtered to remove the majority of salts. The filtrate was concentrated onto Celite® (diatomaceous earth) and eluted through a pre-equilibrated C18 silica gel column (12 g) and eluted with a gradient of 95:5 1% formic acid in water: 1% formic acid in MeCN—10:90 1% formic acid in water: 1% formic acid in MeCN, followed by 100% IPA wash. The fractions containing desired product were concentrated to provide 4-((3-chlorophenyl)amino)-3-hydroxy-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide formate as a white amorphous solid. m/z (ESI) 383.1 (M+H)+.

Workup

  1. extractionextracted with DCM, product
  2. additioneven after addition of brine
  3. customto give product along with salts
  4. filtrationfiltered
  5. customto remove the majority of salts
  6. concentrationThe filtrate was concentrated onto Celite® (diatomaceous earth)
  7. washeluted through a pre-equilibrated C18 silica gel column (12 g)
  8. washeluted with a gradient of 95:5 1% formic acid in water
  9. washwash
  10. additionThe fractions containing desired product
  11. concentrationwere concentrated

Sources & evidence

ORD record
ord-e5c14b6bc9834eed8e5e9c499401401b
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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