Phenol → 5-chloro-4-[(5-chloro-6-phenoxypyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide

HRID 2048030ノート

反応式

HRID 2048030 の反応式
[Cl:1][C:2]1[C:3]([O:16][C:17]2[CH:18]=[N:19][C:20](F)=[C:21]([Cl:23])[CH:22]=2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8].[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O>[Cl:1][C:2]1[C:3]([O:16][C:17]2[CH:18]=[N:19][C:20]([O:31][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:21]([Cl:23])[CH:22]=2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8]

参加物

5

反応物 3

HCID 996PhenolHCID 10796Cesium carbonateHCID 580424375-Chloro-4-[(5-chloro-6-fluoropyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide

生成物 1

HCID 580424275-chloro-4-[(5-chloro-6-phenoxypyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide収率 66.2%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
100 °C

実験手順

To a solution of 5-chloro-4-[(5-chloro-6-fluoropyridin-3-yl)oxy]-2-fluoro-N-(methylsulfonyl)benzamide (Example 19, 100 mg, 0.25 mmol) and phenol (71 mg, 0.76 mmol) in DMSO (1 mL) was added Cs2CO3 (246 mg, 0.76 mmol) at room temperature under N2. The resulting mixture was stirred at 100° C. for 45 minutes. The reaction mixture was allowed to cool to room temperature. The reaction was quenched with water, and acidified with 1N aqueous citric acid solution. The mixture was extracted with DCM (3×3 mL) and filtered through a phase separation cartridge. The organic phase was washed with brine (3 mL), and filtered through a phase separation cartridge. The filtrate was dried by N2 blowing to give a crude product that was purified by reverse phase column chromatography eluting with 5-95% CH3CN in water to give a crude white solid. The solid was purified using trituration with heptane/acetone 9/1 to give the title compound (78 mg, 65%) as a white solid.

後処理

  1. temperatureto cool to room temperature
  2. customThe reaction was quenched with water
  3. extractionThe mixture was extracted with DCM (3×3 mL)
  4. filtrationfiltered through a phase separation cartridge
  5. washThe organic phase was washed with brine (3 mL)
  6. filtrationfiltered through a phase separation cartridge
  7. dry with materialThe filtrate was dried by N2 blowing
  8. customto give a crude product that
  9. customwas purified by reverse phase column chromatography
  10. washeluting with 5-95% CH3CN in water
  11. customto give a crude white solid
  12. customThe solid was purified

出典と根拠

ORDレコード
ord-e62f76ec49214619923b00e97997449a
出典データセット
uspto-grants-2013_11
特許番号
US08592629B2

反応ノート

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