2-Chlorobenzoxazole → 4-[4'-(1,3-Benzoxazol-2-ylamino)-1,1'-biphenyl-4-yl]4-oxo-2-(2-phenylethyl)butanoic acid

HRID 9601

反応式

HRID 9601 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:30])[CH2:15][CH:16]([CH2:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:17]([O:19]CC)=[O:18])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:32]1[O:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[O:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=[C:32]1[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14](=[O:30])[CH2:15][CH:16]([CH2:22][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:17]([OH:19])=[O:18])=[CH:12][CH:13]=2)=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 119862-ChlorobenzoxazoleHCID 14798Sodium HydroxideHCID 21985715Ethyl 4-(4'-amino-1,1'-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate

生成物 1

HCID 113178184-[4'-(1,3-Benzoxazol-2-ylamino)-1,1'-biphenyl-4-yl]4-oxo-2-(2-phenylethyl)butanoic acid収率 33%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

A solution of ethyl 4-(4′-amino-1,1′-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate (100 mg, 0.25 mmol) and 2-chlorobenzoxazole (38.3 mg, 0.25 mmol) in toluene (1.0 mL) was heated at reflux for 16 h. Solvent was removed under reduced pressure, and the residue was dissolved in dichloromethane. The solution was washed with water, solvent was again removed under reduced pressure, and the residue was dissolved in methanol (1 mL) and tetrahydrofuran (1 mL). A 1 N aqueous solution of sodium hydroxide (0.77 mL, 0.77 mmol) was added, and the mixture was stirred at rt for 16 h and then concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 4-[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]4-oxo-2-(2-phenylethyl)butanoic acid (40 mg, 33% yield). LC-MS ret. time 4.14 min, m/z 519.5 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.82–1.90 (m, 2H), 2.68 (m, 2H), 2.80–2.85 (m, 1H), 3.16 (dd, 1H), 3.41 (m, 1H), 7.10–7.30 (m, 8H), 7.48 (t, 2H), 7.78–7.86 (m, 4H), 7.89 (d, 2H), 8.02 (d, 2H), 10.83 (br s, 1H).

後処理

  1. temperatureat reflux for 16 h
  2. customSolvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in dichloromethane
  4. washThe solution was washed with water, solvent
  5. customwas again removed under reduced pressure
  6. dissolutionthe residue was dissolved in methanol (1 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

出典と根拠

ORDレコード
ord-76471614d22c4503b487026d147d7e22
出典データセット
uspto-grants-2006_08
特許番号
US07091228B2

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