Lithium Hexamethyldisilazide → N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

HRID 528521Notes

Reaction equation

HRID 528521 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:11][N:10]=[CH:9][N:8]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][C:30]=1[N+:39]([O-:41])=[O:40]>C1COCC1>[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][N:6]([C:7]1[S:11][N:10]=[CH:9][N:8]=1)[S:35]([C:32]1[CH:33]=[CH:34][C:29]([F:28])=[C:30]([N+:39]([O-:41])=[O:40])[CH:31]=1)(=[O:36])=[O:37]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27827994-Fluoro-3-nitrobenzene-1-sulfonyl chlorideHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine2×

Product 1

HCID 71259496N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 100-mL round-bottom flask was charged with N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (INTERMEDIATE A, 1.478 g, 5.88 mmol) and THF (10 mL) to give a clear, light-yellow solution. The flask was cooled in a dry ice-acetone bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (5.88 mL, 5.88 mmol) was added dropwise over 2 min. The cooling bath was removed for 5 minutes, then re-cooled for 5 min. A solution of 4-fluoro-3-nitrobenzene-1-sulfonyl chloride (1.281 g, 5.35 mmol) in THF (3 mL with a 1 mL flask/syringe wash) was added dropwise over 2 minutes. The cooling bath was removed and the reaction was warmed to room temperature. The mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over sodium sulfate, filtered, and concentrated. The material was concentrated from EtOAc (2×), then taken up in EtOAc, sonicated for 1 min, and filtered through a membrane filter. The resulting solid was transferred to a sonication vial, then put under high vacuum at 60° C. for 10 min to give N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (INTERMEDIATE S) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ=8.24 (s, 1 H), 8.18 (dd, J=2.4, 6.7 Hz, 1 H), 7.99 (ddd, J=2.4, 3.9, 8.8 Hz, 1H), 7.33-7.28 (m, 1 H), 7.09 (d, J=8.4 Hz, 1 H), 6.32 (dd, J=2.3, 8.4 Hz, 1 H), 6.21 (d, J=2.4 Hz, 1 H), 5.37 (s, 2 H), 3.76 (s, 3 H), 3.63 (s, 3 H). m/z (ESI) 477.0 (M+Na)+.

Workup

  1. customto give a clear, light-yellow solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 10 min
  3. customThe cooling bath was removed for 5 minutes
  4. temperaturere-cooled for 5 min
  5. customThe cooling bath was removed
  6. additionThe mixture was diluted with water
  7. extractionextracted with EtOAc
  8. extractionThe organic extract
  9. washwas washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. concentrationThe material was concentrated from EtOAc (2×)
  14. customsonicated for 1 min
  15. filtrationfiltered through a membrane
  16. filtrationfilter

Sources & evidence

ORD record
ord-916d42a87fff4206962c4de78f6d6a09
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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