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

HRID 1619693Notes

Reaction equation

HRID 1619693 reaction equation
[Cl:1][C:2]1[C:3]([O:29][C:30]2[CH:31]=[C:32]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])[C:33]([Cl:37])=[CH:34][C:35]=2I)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1.C([Sn](CCCC)(CCCC)[C:50]1[CH:55]=[CH:54][N:53]=[N:52][CH:51]=1)CCC.[F-].[Cs+].C(#N)C>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I>[Cl:1][C:2]1[C:3]([O:29][C:30]2[CH:31]=[C:32]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[F:44])[C:33]([Cl:37])=[CH:34][C:35]=2[C:50]2[CH:55]=[CH:54][N:53]=[N:52][CH:51]=2)=[CH:4][C:5]([F:28])=[C:6]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[C:12]2[S:13][CH:14]=[N:15][N:16]=2)(=[O:10])=[O:9])[CH:7]=1

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 580422945-chloro-4-(6-chloro-2'-fluoro-4-iodobiphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide

Product 1

HCID 580422495-chloro-4-(6-chloro-2'-fluoro-4-(pyridazin-4-yl)biphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamideYield 39%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Tetrakistriphenylphosphinepalladium (0) (44 mg, 0.038 mmol) and copper (I) iodide (29 mg, 0.152 mmol) were added to a degassed mixture of 5-chloro-4-(6-chloro-2′-fluoro-4-iodobiphenyl-3-yloxy)-N-(2,4-dimethoxybenzyl)-2-fluoro-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide (Preparation 93, 600 mg, 0.759 mmol), 4-(tributylstannyl)pyridazine (364 mg, 0.987 mmol), caesium fluoride (230 mg, 1.52 mmol), and acetonitrile (5.0 mL). The reaction was heated at 45° C. for 18 hours and then the cooled reaction mixture was diluted with ethyl acetate (30 mL) and filtered through Arbocel. The filtrate was then washed with water (5 mL), brine (5 mL), dried over MgSO4, filtered and evaporated. The residue was purified by preparative HPLC using acetonitrile/water as eluent (15/85 to 95/5, Phenomenex Luna C18 5 u 110 A 21.2×150 mm) to give the title compound (220 mg, 39%) as a brown foam.

Workup

  1. customthe cooled reaction mixture
  2. filtrationfiltered through Arbocel
  3. washThe filtrate was then washed with water (5 mL), brine (5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-65c8be6e5aae406cad3e9d75ca18d5ad
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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