반응 #1933458

반응 방정식

potassium hydroxide

iodine

2-amino-N-(4-sec-butylphenyl)-benzamide

4-hydroxy-benzaldehyde

→

3-(4-sec-butylphenyl)-2-(4-hydroxyphenyl)-3H-quinazolin-4-one

용매

N,N-dimethylformamide

반응 조건

후처리

1. 1
   기타the solvent was removed under reduced pressure
2. 2
   workup.ADDITIONthe residue was diluted with ethyl acetate
3. 3
   세척washed with water
4. 4
   건조dried over sodium sulfate
5. 5
   기타The crude oil (0.97 g) was purified by column chromatography (silica gel 230-400 mesh; 1/1 hexanes/EtOAc as eluent)

실험 절차

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).

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