反应详情

2-(7-Methyl-4-(piperazin-1-yl)quinazolin-2-yl)phenol (87 mg, 0.27 mmol), 4,4,4-trifluoro-2-hydroxybutanoic acid (43 mg, 0.27 mmol), HATU (0.12 g, 0.33 mmol) and triethylamine (45 μL, 0.33 mmol) were stirred in DMF (3 mL) at room temperature overnight. The mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine and water, dried over Na2SO4 and concentrated. Purification via silica gel chromatography using 0-20% EtOAc in 1:1 CH2Cl2: hexanes gave 4,4,4-trifluoro-2-hydroxy-1-(4-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperazin-1-yl)butan-1-one as an off-white solid (86 mg, 66%). 1H NMR (400 MHz, CDCl3) δ 8.46 (dd, J=8.0, 1.7 Hz, 1H), 7.77 (d, J=8.5 Hz, 1H), 7.70 (s, 1H), 7.41-7.37 (m, 1H), 7.31 (dd, J=8.5, 1.5 Hz, 1H), 7.05-7.03 (m, 1H), 6.97-6.93 (m, 1H), 4.80-4.75 (m, 1H), 4.07-3.68 (m, 9H), 2.56 (s, 3H), 2.50-2.39 (m, 2H); LC/MS: m/z 461.3 (M+H)+ at 2.49 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

1. extractionextracted with EtOAc
2. washThe combined organic layers were washed with brine and water
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. customPurification via silica gel chromatography