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 1619693노트

반응식

HRID 1619693 반응식
[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

참가 물질

8

반응물 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

생성물 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)benzenesulfonamide수율 39%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
45 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-65c8be6e5aae406cad3e9d75ca18d5ad
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772293B2

반응 노트

불러오는 중…