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

HRID 1808191

反応式

HRID 1808191 の反応式
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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 57417360Sodium chloride; water溶媒

反応条件

温度
-78 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-5d150023172042c38609c17a69f9decb
出典データセット
uspto-grants-2013_01
特許番号
US08357711B2

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