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

HRID 30918

Reaction equation

HRID 30918 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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]-4oxo-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).

Workup

  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)

Sources & evidence

ORD record
ord-2dcc4e30bd0444e5861c85b924c8b106
Source dataset
uspto-grants-2008_09
Patent number
US07423156B2

Linked notes

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