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

HRID 51966

反応式

HRID 51966 の反応式
[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]

参加物

5

反応物 4

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

生成物 1

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

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-73b17bf7c0474960b51461ff373804ab
出典データセット
uspto-grants-2004_03
特許番号
US06713489B2

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