Acetic Acid → 7-[(4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester

HRID 431356

Reaction equation

HRID 431356 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]([C:13]2[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:12])[CH:5]=[CH:6][C:7]=1C=O.[CH2:29]([O:31][C:32](=[O:36])[CH:33]=[CH:34]O)[CH3:30].[Na].[C:38](O)(=O)C>>[CH2:29]([O:31][C:32]([C:33]1[CH:38]=[N:1][C:2]2[C:7]([CH:34]=1)=[CH:6][CH:5]=[C:4]([NH:10][C:11]([C:13]1[C:14]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:27])([F:26])[F:28])=[CH:21][CH:20]=3)=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:12])[CH:3]=2)=[O:36])[CH3:30]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 428818beta-Hydroxyacrylic acid ethyl ester3×HCID 5360545Sodium3×HCID 101346044'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide

Product 1

HCID 101832717-[(4'-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester

Procedure

A solution of 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide (7 g, 18.2 mmol, 1 equiv) and 3-hydroxy-acrylic acid ethyl ester, sodium salt (2.52 g, 18.2 mmol, 1 equiv) in glacial acetic acid (70 mL, 10 volumes) was heated at 80° C. for 2 hours. Additional 3-hydroxy-acrylic acid ethyl ester, sodium salt (2.52 g, 18.2 mmol, 1 equiv) was added and the solution heated for 15 hours. Again, additional 3-hydroxy-acrylic acid ethyl ester, sodium salt (1.26 g, 9.1 mmol, 0.5 equiv) was added and the solution heated for another 4 hours. The reaction mixture was concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and the organic layer was washed with a saturated aqueous sodium carbonate solution (2×200 mL) and 1 N NaOH solution (200 mL). The combined aqueous layers were back extracted with ethyl acetate (200 mL). The combined organic layers were dried over sodium sulfate and treated with Darco G-60® (7 g). The solids were removed by filtration and the filtrate was concentrated to afford crude 7-[(4′-trifluoromethyl-biphenyl-2-carbonyl)-amino]-quinoline-3-carboxylic acid ethyl ester, which was used in the next step without further purification.

Workup

  1. temperaturethe solution heated for 15 hours
  2. temperaturethe solution heated for another 4 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (300 mL)
  5. washthe organic layer was washed with a saturated aqueous sodium carbonate solution (2×200 mL) and 1 N NaOH solution (200 mL)
  6. extractionThe combined aqueous layers were back extracted with ethyl acetate (200 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. additiontreated with Darco G-60® (7 g)
  9. customThe solids were removed by filtration
  10. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-628267fd1966415d9779148ddd228b41
Source dataset
uspto-grants-2003_12
Patent number
US06657065B2

Linked notes

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