2-Chloroethanol → 3-(4-sec-butylphenyl)-2-(4-(2-hydroxyethoxy)phenyl)quinazolin-4(3H)-one

HRID 1846277Notes

Reaction equation

HRID 1846277 reaction equation
[CH:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]2[C:22]2[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=2)=[CH:7][CH:6]=1)([CH2:3][CH3:4])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:36][CH2:37][OH:38]>CN(C)C=O>[CH:1]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]2[C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:36][CH2:37][OH:38])=[CH:26][CH:27]=2)=[CH:9][CH:10]=1)([CH2:3][CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 342-ChloroethanolHCID 11430Potassium CarbonateHCID 1363307883-(4-sec-butylphenyl)-2-(4-hydroxyphenyl)-3H-quinazolin-4-one

Product 1

HCID 468406123-(4-sec-butylphenyl)-2-(4-(2-hydroxyethoxy)phenyl)quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-amino-N-(4-sec-butylphenyl)-benzamide (0.500 g, 1.86 mmol) in N,N-dimethylformamide (9 mL) under nitrogen atmosphere was added 4-hydroxy-benzaldehyde (0.450 g, 3.73 mmol) followed by iodine (0.560 g, 2.23 mmol) and potassium hydroxide (0.120 g, 2.23 mmol). The resulting mixture was heated at 110° C. overnight, then the solvent was removed under reduced pressure, the residue was diluted with ethyl acetate, washed with water and dried over sodium sulfate. The crude oil (0.97 g) was purified by column chromatography (silica gel 230-400 mesh; 1/1 hexanes/EtOAc as eluent) to give pure 3-(4-sec-butylphenyl)-2-(4-hydroxyphenyl)-3H-quinazolin-4-one as a yellow solid. Yield: 0.33 g (47.8%). To a mixture of 3-(4-sec-butylphenyl)-2-(4-hydroxyphenyl)-3H-quinazolin-4-one (0.11 g, 0.31 mmol) and potassium carbonate (0.13 g, 0.93 mmol) in N,N-dimethylformamide (3.5 mL) under nitrogen atmosphere was added 2-chloroethanol (0.032 mL, 46 mmol). The reaction mixture was heated at reflux for 14 hours, then the solvent was removed under reduced pressure and the residue was diluted with ethyl acetate, washed with 5% aqueous solution of sodium hydroxide, brine, and dried over sodium sulfate. The crude solid (0.13 g) was purified by column chromatography (silica gel 230-400 mesh; 10/0 to 1/1 hexanes/EtOAc, then 10/0 to 9.4/0.6 methylene chloride/MeOH as eluent) and triturated with Et2O to give the pure title compound as a light brown solid. Yield: 60 mg, (46.3%). MP 172.8-174.9° C. 1H-NMR (400 MHz, CDCl3): δ 8.35 (d, 1H), 7.80 (d, 2H), 7.50 (m, 1H), 7.28 (d, 2H), 7.14 (d, 2H), 7.05 (d, 2H), 6.72 (d, 2H), 4.00 (m, 2H), 3.95 (m, 2H), 2.58 (m, 1H), 1.95 (s, OH), 1.65-1.48 (m, 2H), 1.20 (d, 3H), 0.75 (t, 3H). MS (ES+) m/z: 415.09 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 14 hours
  3. customthe solvent was removed under reduced pressure
  4. additionthe residue was diluted with ethyl acetate
  5. washwashed with 5% aqueous solution of sodium hydroxide, brine
  6. dry with materialdried over sodium sulfate
  7. customThe crude solid (0.13 g) was purified by column chromatography (silica gel 230-400 mesh
  8. custom10/0 to 1/1 hexanes/EtOAc, then 10/0 to 9.4/0.6 methylene chloride/MeOH as eluent) and triturated with Et2O

Sources & evidence

ORD record
ord-1660e87c8f9b43189fa568271328e49a
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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