4-Bromobenzenesulfonamide → 4-(2-(3-Azabicyclo[3.1.0]hexan-3-ylmethyl)-4-(4-chlorophenyl)thiazol-5-yl)benzenesulfonamide

HRID 1051899Notes

Reaction equation

HRID 1051899 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C([O-])(=O)C.[K+].[CH:17]12[CH2:22][CH:21]1[CH2:20][N:19]([CH2:23][C:24]1[S:25][CH:26]=[C:27]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[N:28]=1)[CH2:18]2>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(N(C)C)=O>[CH:21]12[CH2:22][CH:17]1[CH2:18][N:19]([CH2:23][C:24]1[S:25][C:26]([C:2]3[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][CH:3]=3)=[C:27]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[N:28]=1)[CH2:20]2

Participants

6

Reactant 3

HCID 696964-BromobenzenesulfonamideHCID 517044Potassium AcetateHCID 89813117HCID 89813117, compound2×

Product 1

HCID 717353984-(2-(3-Azabicyclo[3.1.0]hexan-3-ylmethyl)-4-(4-chlorophenyl)thiazol-5-yl)benzenesulfonamideYield 22%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

4-bromobenzenesulfonamide (0.37 g, 1.57 mmol) and potassium acetate (0.28 g, 2.87 mmol) were added to a solution of 2-(3-azabicyclo[3.1.0]hexan-3-ylmethyl)-4-(4-chlorophenyl)thiazole (Step-2 of compound 102, 0.42 g, 1.43 mmol) in a DMA (5 ml) in a tube at 25° C. Nitrogen gas was bubbled through the reaction mixture for 15 minutes. Palladium acetate (0.032 g, 0.14 mmol) was then added to the reaction mixture under nitrogen atmosphere and the tube was sealed. The reaction mixture was heated at 150° C. for 20 hrs under stirring. The progress of the reaction was monitored by TLC. The reaction mixture was then cooled to 25° C. and filtered through celite. The celite cake was washed with ethyl acetate (20 ml). The combined filtrate was concentrated under reduced pressure to obtain a crude product, which was then purified by column chromatography using 30% ethyl acetate in hexanes as an eluent to obtain the title compound (0.14 g, 21.4%). MS: m/z 446 (M+1).

Workup

  1. customNitrogen gas was bubbled through the reaction mixture for 15 minutes
  2. customthe tube was sealed
  3. temperatureThe reaction mixture was then cooled to 25° C.
  4. filtrationfiltered through celite
  5. washThe celite cake was washed with ethyl acetate (20 ml)
  6. concentrationThe combined filtrate was concentrated under reduced pressure
  7. customto obtain a crude product, which
  8. customwas then purified by column chromatography

Sources & evidence

ORD record
ord-53a1ef27cef4423db3f70cb0fc59f3a3
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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