Lithium → 3-Fluoro-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]benzoic acid

HRID 401770

Reaction equation

HRID 401770 reaction equation
COC1C=C(OC)C=CC=1C[NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1.[Li].Cl[S:20]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][C:24]=1[F:32])(=[O:22])=[O:21]>C1COCC1.[Cl-].[Na+].O>[F:32][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:23]=1[S:20]([NH:6][C:7]1[S:11][N:10]=[CH:9][N:8]=1)(=[O:22])=[O:21])[C:27]([OH:29])=[O:28]

Participants

6

Reactant 3

HCID 3028194LithiumHCID 113109714-(Chlorosulfonyl)-3-fluorobenzoic acidHCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

Product 1

HCID 577320643-Fluoro-4-[(1,2,4-thiadiazol-5-ylamino)sulfonyl]benzoic acidYield 16%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 26, 500 mg, 2.1 mmol, 1.0 eq) was dissolved in THF (10 ml) and cooled to −78° C. 1,1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 4.2 ml, 4.19 mmol, 2.0 eq) was added dropwise and the reaction mixture stirred for a further 10 minutes. A solution of 4-(chlorosulfonyl)-3-fluorobenzoic acid (Preparation 9, 500 mg, 2.1 mmol, 1 eq) in THF (3 ml) was added dropwise and the reaction mixture stirred at −78° C. for 1 hour then at room temperature for 18 hours. The reaction mixture was diluted with brine, extracted into ethyl acetate, dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was passed through a SCX cartridge to remove remaining amine. The material was redissolved in 4M HCl in dioxane and stirred at room temperature for 2 hours. The resulting precipitate was collected by filtration and washed with diethylether to yield the title compound (100 mg, 0.33 mmol, 16%).

Workup

  1. stirringthe reaction mixture stirred at −78° C. for 1 hour
  2. waitat room temperature for 18 hours
  3. extractionextracted into ethyl acetate
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto remove
  8. dissolutionThe material was redissolved in 4M HCl in dioxane
  9. stirringstirred at room temperature for 2 hours
  10. filtrationThe resulting precipitate was collected by filtration
  11. washwashed with diethylether

Sources & evidence

ORD record
ord-b02317c19ec341018c4af3458b9a817a
Source dataset
uspto-grants-2014_06
Patent number
US08741934B2

Linked notes

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