Ammonium Chloride → 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 2283625Notes

Reaction equation

HRID 2283625 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[N:10][N:11]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35](Cl)(=[O:37])=[O:36])[CH:34]=1.[Cl-].[NH4+]>O1CCCC1>[Cl:28][C:29]1[C:30]([F:40])=[CH:31][C:32]([F:39])=[C:33]([S:35]([N:6]([CH2:5][C:4]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:3]=2[O:2][CH3:1])[C:7]2[S:8][CH:9]=[N:10][N:11]=2)(=[O:37])=[O:36])[CH:34]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27735275-Chloro-2,4-difluorobenzenesulphonyl chlorideHCID 58042278N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideYield 73.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 5, 899 mg, 3.58 mmol) in tetrahydrofuran (6.0 mL) cooled to −78° C., was added lithium hexamethyldisilazide (1.0 M in tetrahydrofuran, 4.3 mL) dropwise. The reaction mixture was stirred for 35 minutes at ambient temperature, then cooled again to −78° C. before the dropwise addition of 5-chloro-2,4-difluorobenzenesulfonyl chloride (850 mg, 3.4 mmol). The reaction mixture was stirred at −78° C. for 1 hour then at ambient temperature for 4 hours. The reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with dichloromethane. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by automated silica gel flash chromatography (0% to 10% ethyl acetate in hexanes gradient elution) to afford the title compound as a white solid (1.16 g, 73%).

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 1 hour
  2. waitat ambient temperature for 4 hours
  3. extractionextracted with dichloromethane
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by automated silica gel flash chromatography (0% to 10% ethyl acetate in hexanes gradient elution)

Sources & evidence

ORD record
ord-a309d6c78037421fb8893568e7cc93b0
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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