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Dimethyl Sulfoxide → 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

HRID 1401937
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HRID 1401937 반응식
[Cl:1][C:2]1[C:3](F)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.[F:30][C:31]1[C:32]([C:44]([F:47])([F:46])[F:45])=[CH:33][C:34]([C:38]2[CH:43]=[CH:42][N:41]=[N:40][CH:39]=2)=[C:35]([OH:37])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O.[Cl-].[NH4+]>[Cl:1][C:2]1[C:3]([O:37][C:35]2[CH:36]=[C:31]([F:30])[C:32]([C:44]([F:47])([F:45])[F:46])=[CH:33][C:34]=2[C:38]2[CH:43]=[CH:42][N:41]=[N:40][CH:39]=2)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:9])=[O:10])[CH:7]=1
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참가 물질

7

반응물 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 1360636295-Fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol

생성물 1

HCID 866438255-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide
수율 23%

시약·촉매·용매 2

HCID 962Water용매HCID 25517Ammonium Chloride용매

실험 절차

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 247, 63 mg, 0.14 mmol) was added to a mixture of 5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenol (Preparation 884, mg, 0.14 mmol) and potassium carbonate (22 mg, 0.16 mmol) in dimethyl sulfoxide (2 mL, 30 mmol). The reaction mixture was stirred at ambient temperature. After 3 hours the reaction mixture was diluted with water and saturated aqueous ammonium chloride and extracted with ethyl acetate (3×). The combined organic layers were washed with water then brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in methylene chloride, concentrated onto diatomaceous earth, and purified by automated flash chromatography (12 g SiO2, hexanes to ethyl acetate) to afford the intermediate 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide as a glass (22 mg, 23%).

후처리

  1. customPreparation 884
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with water
  4. dry with materialbrine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. concentrationconcentrated onto diatomaceous earth
  8. custompurified by automated flash chromatography (12 g SiO2, hexanes to ethyl acetate)

출처 및 근거

ORD 기록
ord-9a548b3d54cb4915aa649fa01f34784a
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08907101B2

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