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 1619693ノート

反応式

HRID 1619693 の反応式
[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

参加物

8

反応物 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

生成物 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)benzenesulfonamide収率 39%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
45 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-65c8be6e5aae406cad3e9d75ca18d5ad
出典データセット
uspto-grants-2014_07
特許番号
US08772293B2

反応ノート

読み込み中…