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

HRID 1051893Notes

Reaction equation

HRID 1051893 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[S:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=3[F:19])[N:11]=1)[CH2:2]2.Br[C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH2:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1.C([O-])(=O)C.[K+]>CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:5]12[CH2:6][CH:1]1[CH2:2][N:3]([C:7]1[S:8][C:9]([C:21]3[CH:26]=[CH:25][C:24]([S:27]([NH2:30])(=[O:29])=[O:28])=[CH:23][CH:22]=3)=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=3[F:19])[N:11]=1)[CH2:4]2

Participants

6

Reactant 3

HCID 696964-BromobenzenesulfonamideHCID 517044Potassium AcetateHCID 89813524HCID 89813524, compound2×

Product 1

HCID 717370094-(2-(3-Azabicyclo[3.1.0]hexan-3-yl)-4-(2,4-difluorophenyl)thiazol-5-yl)benzenesulfonamideYield 24.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(2,4-difluorophenyl)thiazole (Step 2 of compound 66, 0.23 g, 0.82 mmol) in dimethyl acetamide (5 ml) were added 4-bromobenzenesulfonamide (0.21 g, 0.90 mmol) and potassium acetate (0.16 g, 1.65 mmol) at 25° C. in a tube, the nitrogen gas was bubbled through reaction mixture for 15 minutes. To the reaction mixture was added palladium (II) acetate (0.019 gm, 0.08 mmol) under nitrogen and the reaction mixture was heated at 150° C. for 15 hr with stirring. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 ml). The reaction mixture was washed with water (2×10 ml), dried over sodium sulphate and concentrated under reduced pressure to obtain a crude product; which was purified by flash column chromatography using 40% ethyl acetate in hexanes as an eluent to obtain the title compound (0.088 g, 24.5%). MS: m/z 434 (M+1).

Workup

  1. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customThe progress of reaction
  3. temperatureThe reaction mixture was cooled to 25° C.
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate (50 ml)
  6. washThe reaction mixture was washed with water (2×10 ml)
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customto obtain a crude product
  10. customwhich was purified by flash column chromatography

Sources & evidence

ORD record
ord-dd0ddbef989448099ea7241a69ae81b3
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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