Water → 5-Chloro-4-(6-chloro-4'-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

HRID 1619702Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1619702
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][C:5]([OH:15])=[C:4]([C:16]2[CH:21]=[CH:20][N:19]=[N:18][CH:17]=2)[CH:3]=1.[Cl:22][C:23]1[C:24](F)=[CH:25][C:26]([F:49])=[C:27]([S:29]([N:32]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][C:40]=2[O:47][CH3:48])[C:33]2[S:34][CH:35]=[N:36][N:37]=2)(=[O:31])=[O:30])[CH:28]=1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[Cl:22][C:23]1[C:24]([O:15][C:5]2[CH:6]=[C:7]([C:8]3[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=3)[C:2]([Cl:1])=[CH:3][C:4]=2[C:16]2[CH:21]=[CH:20][N:19]=[N:18][CH:17]=2)=[CH:25][C:26]([F:49])=[C:27]([S:29]([N:32]([CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][C:40]=2[O:47][CH3:48])[C:33]2[S:34][CH:35]=[N:36][N:37]=2)(=[O:30])=[O:31])[CH:28]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 580422535-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideHCID 1362008786-Chloro-4'-fluoro-4-(pyridazin-4-yl)biphenyl-3-ol

Produkt 1

HCID 580422795-Chloro-4-(6-chloro-4'-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Versuchsvorschrift

6-Chloro-4′-fluoro-4-(pyridazin-4-yl)biphenyl-3-ol (Preparation 102, 150 mg, 0.50 mmol), 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 16, 345 mg, 0.75 mmol), and potassium carbonate (207 mg, 1.50 mmol) were suspended in dimethyl sulfoxide (2 mL). The reaction mixture was stirred for 18 hours at room temperature. Water (50 mL) was added and the suspension was extracted with ethyl acetate (2×50 mL) and dichloromethane (3×50 mL). The organic layers were combined, dried over MgSO4, filtered and evaporated. The residue was purified by semi preparative reverse phase HPLC (solvent A: 0.05% formic acid in acetonitrile; solvent B: 0.05% formic acid in water; flow rate: 15 mL/min; gradient 0 min 5% A, 2.5 min 5% A, 22.5 min 95% A, 32.5 min 95% A then return to initial conditions) to afford the title compound (100 mg, 27%) as a glass.

Aufarbeitung

  1. extractionthe suspension was extracted with ethyl acetate (2×50 mL) and dichloromethane (3×50 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by semi preparative reverse phase HPLC (solvent A
  6. customgradient 0 min 5% A, 2.5 min 5% A, 22.5 min 95% A, 32.5 min 95% A

Quellen und Nachweise

ORD-Eintrag
ord-9fca5bc0d9ca463d8ea26b6bf7a108f0
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772293B2

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