Sodium Hydroxide → 4,4,4-Trifluoro-3-(3-fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)butanoic acid

HRID 418700ノート

反応式

HRID 418700 の反応式
[F:1][C:2]([F:40])([F:39])[CH:3]([CH:28](C(OCC)=O)[C:29]([O:31]CC)=[O:30])[NH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[CH:18]=[C:19]([C:21]4[N:22]=[CH:23][N:24]([CH3:26])[CH:25]=4)[S:20][C:13]=23)=[C:7]([F:27])[CH:6]=1.[OH-].[Na+]>O.C(O)C>[F:40][C:2]([F:1])([F:39])[CH:3]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[CH:18]=[C:19]([C:21]4[N:22]=[CH:23][N:24]([CH3:26])[CH:25]=4)[S:20][C:13]=23)=[C:7]([F:27])[CH:6]=1)[CH2:28][C:29]([OH:31])=[O:30]

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 58790129Diethyl 2-(2,2,2-trifluoro-1-(3-fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)ethyl)malonate

生成物 1

HCID 587904194,4,4-Trifluoro-3-(3-fluoro-4-(2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenylamino)butanoic acid収率 37%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

A solution of 319 (490 mg, 0.84 mmol) and sodium hydroxide (338 mg, 8.44 mmol) in water (0.7 mL) and ethanol (3.4 mL) was stirred at room temperature for 48 h. The solvents were removed under reduced pressure and the residue was dissolved in water (20 mL). The solution was neutralized to pH 4 with a 3N HCl solution and the solid thus formed was filtered off, rinsed with water and dried. The solid was suspended in dry toluene (20 mL), heated to reflux for 1 h under continuous stirring, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent MeOH-dichloromethane, gradient 10:90 to 50:50) and the resulting solid was triturated in a mixture of dichloromethane, ethyl acetate and hexane, isolated by filtration, and dried under high vacuum to afford title compound 320 (150 mg, 0.31 mmol, 37% yield). LRMS (M+1) 480.9 (100%).

後処理

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe residue was dissolved in water (20 mL)
  3. customthe solid thus formed
  4. filtrationwas filtered off
  5. washrinsed with water
  6. customdried
  7. temperatureheated
  8. temperatureto reflux for 1 h under continuous stirring
  9. customthe solvent was removed under reduced pressure
  10. customThe residue was purified by column chromatography on silica gel (eluent MeOH-dichloromethane, gradient 10:90 to 50:50)
  11. customthe resulting solid was triturated in a mixture of dichloromethane, ethyl acetate and hexane
  12. customisolated by filtration
  13. customdried under high vacuum

出典と根拠

ORDレコード
ord-d48e9fa274a24a298d2eb749a7cb7944
出典データセット
uspto-grants-2012_01
特許番号
US08093264B2

反応ノート

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