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 418700Notes

Reaction equation

HRID 418700 reaction equation
[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]

Participants

5

Reactant 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

Product 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 acidYield 37%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-d48e9fa274a24a298d2eb749a7cb7944
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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