Dimethyl Sulfoxide → 4-{4-Chloro-2-[2-(dimethylamino)pyridin-4-yl]phenoxy}-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 1692225Notes

Reaction equation

HRID 1692225 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([S:10]([NH:13][C:14]2[S:18][N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([N:33]([CH3:35])[CH3:34])[CH:28]=2)[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O.[Cl-].[NH4+]>>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:8]2[CH:7]=[CH:6][C:5]([S:10]([NH:13][C:14]3[S:18][N:17]=[CH:16][N:15]=3)(=[O:12])=[O:11])=[CH:4][C:3]=2[C:1]#[N:2])=[C:22]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([N:33]([CH3:35])[CH3:34])[CH:28]=2)[CH:21]=1

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 580423023-cyano-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamideHCID 1360636144-Chloro-2-[2-(dimethylamino)pyridin-4-yl]phenol

Product 1

HCID 468417864-{4-Chloro-2-[2-(dimethylamino)pyridin-4-yl]phenoxy}-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamideYield 60%

Procedure

3-Cyano-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (Preparation 65, 40 mg, 0.14 mmol), 4-chloro-2-[2-(dimethylamino)pyridin-4-yl]phenol (Preparation 865, 35.0 mg, 0.141 mmol) and potassium carbonate (58 mg, 0.42 mmol) in dimethyl sulfoxide (1 mL, 20 mmol) was stirred at 150° C. for 16 hours. The reaction mixture was cooled to ambient temperature and poured into saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with 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 20% methanol in ethyl acetate). The product-containing fractions were concentrated in vacuo then lyophilized from water and minimal acetonitrile to afford the product as a light yellow powder (40 mg, 60%).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. concentrationconcentrated onto diatomaceous earth
  7. custompurified by automated flash chromatography (12 g SiO2, hexanes to 20% methanol in ethyl acetate)
  8. concentrationThe product-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-5dd1e0d2d83d419c9dcc8319951d9bed
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

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