p-Toluenesulfonic acid → 3-(4-sec-butylphenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

HRID 1846260Notes

Reaction equation

HRID 1846260 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH2:15][CH3:16])[CH3:14])=[CH:9][CH:8]=1)=[O:5].[OH:21][CH2:22][CH2:23][O:24][C:25]1[C:32]([CH3:33])=[CH:31][C:28]([CH:29]=O)=[CH:27][C:26]=1[CH3:34].S([O-])(O)=O.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[CH:13]([C:10]1[CH:11]=[CH:12][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:1]=[C:29]2[C:28]2[CH:31]=[C:32]([CH3:33])[C:25]([O:24][CH2:23][CH2:22][OH:21])=[C:26]([CH3:34])[CH:27]=2)=[CH:8][CH:9]=1)([CH2:15][CH3:16])[CH3:14]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 167700372-Amino-N-(4-sec-butylphenyl)benzamideHCID 23665763Sodium BisulfiteHCID 289325784-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde

Product 1

HCID 467007623-(4-sec-butylphenyl)-2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-amino-N-(4-sec-butylphenyl)benzamide (1.27 g, 4.73 mmol) in N,N-dimethyl acetamide (20 mL) were added 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (D) (0.92 g, 4.7 mmol), sodium hydrogen sulphite (58.5 wt %) (0.95 g, 5.2 mmol) and p-toluenesulfonic acid (0.18 g, 0.95 mmol). The reaction mixture was stirred at 120° C. overnight, and cooled to room temperature. The solvent was removed under reduced pressure and water (100 mL) was added. The mixture was extracted with ethyl acetate (200 mL). The organic phase was washed with water (2×100 mL), then brine (100 mL), and dried over anhydrous Na2SO4. Removal of solvent gave crude compound, which was purified by the Simpliflash system (30% ethyl acetate in hexanes as eluent) to give the title compound (E) as a white solid. Yield: 0.34 g (16%). MP 152-153° C. 1H-NMR (400 MHz, CDCl3): δ 8.36-8.34 (m, 1H), 7.81-7.80 (m, 2H), 7.54-7.50 (m, 1H), 7.13 (d, J=6.26 Hz, 2H), 7.06 (d, J=8.21 Hz, 2H), 6.98 (s, 2H), 3.92-3.88 (m, 2H), 3.78-3.76 (m, 2H), 2.56-2.54 (m, 1H), 2.13 (s, 6H), 2.06 (t, J=6.26 Hz, 1H), 1.60-1.48 (m, 2H), 1.20 (d, J=7.04 Hz, 3H), 0.727 (t, J=7.43 Hz, 3H). MS (ES+) m/z: 443.01 (M+1) (100%).

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed under reduced pressure and water (100 mL)
  3. additionwas added
  4. extractionThe mixture was extracted with ethyl acetate (200 mL)
  5. washThe organic phase was washed with water (2×100 mL)
  6. dry with materialbrine (100 mL), and dried over anhydrous Na2SO4
  7. customRemoval of solvent
  8. customgave crude compound, which
  9. customwas purified by the Simpliflash system (30% ethyl acetate in hexanes as eluent)

Sources & evidence

ORD record
ord-453414e49834444590be0ebee5262339
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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