4-Bromothioanisole → 2-[4-(Methylthio)phenyl]-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

HRID 891298Notes

Reaction equation

HRID 891298 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:24])[NH:10][N:11]=[CH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.Br[C:26]1[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=1>N1C=CC=CC=1.O.C(OCC)(=O)C.[Cu]>[CH3:33][S:32][C:29]1[CH:30]=[CH:31][C:26]([N:10]2[C:9](=[O:24])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[C:13]([C:14]3[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=3)[CH:12]=[N:11]2)=[CH:27][CH:28]=1

Participants

7

Reactant 2

HCID 660374-BromothioanisoleHCID 102911854-(4-Fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone

Product 1

HCID 103222982-[4-(Methylthio)phenyl]-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinoneYield 81.5%

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 962WaterSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the product from Example 11, 4-(4-Fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (344 mg, 1.0 mmol), 4-bromothioanisole (812 mg, 4.0 mmol), and copper (70 mg, 1.1 mmol) in 20 mL of pyridine was stirred at reflux under a nitrogen atmosphere for 18 hours. After cooling to room temperature, the reaction mixture was diluted with a mixture of water and ethyl acetate. The two layers were filtered through Celite®, and separated. The organic layer was washed with 10% aqueous citric acid, with brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo and the residue purified by column chromatography (silica gel, 93:7 dichloromethane/ethyl acetate) to provide the title compound as a foam (yield: 380 mg, 81.5%). 1H NMR (300 MHz, CDCl3) δ 2.55 (s, 3H), 3.05 (s, 3H), 6.98 (t, J=9 Hz, 2H), 7.22 (dd, J=9 Hz, 6 Hz, 2H), 7.38 (dd, J=8 Hz, 2 Hz, 4H), 7.64 (d, J=9 Hz, 2H), 7.91 (d, J=9 Hz, 2H), 7.98 (s, 1H). MS (DCI/NH3) m/z 467 (M+H)+. Anal. calc. for C24H19FN2O3S2.0.5H2O: C, 60.63; H, 4.21; N, 5.90. Found: C, 60.72; H, 3.96; N, 5.70.

Workup

  1. temperatureat reflux under a nitrogen atmosphere for 18 hours
  2. filtrationThe two layers were filtered through Celite®
  3. customseparated
  4. washThe organic layer was washed with 10% aqueous citric acid, with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue purified by column chromatography (silica gel, 93:7 dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-811eaf9291ab4e22a40a6e46a104eb04
Source dataset
uspto-grants-2006_02
Patent number
US07001895B2

Reaction notes

Loading…