反应详情

To a solution of N4-((8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methyl)-N2-(diphenylmethylene)-5-fluoropyrimidine-2,4-diamine (0.1370 g, 0.237 mmol) in 6 ml of MeOH at room temperature was added sodium acetate anhydrous (0.0661 g, 0.805 mmol) followed by hydroxylamine hydrochloride (0.0461 g, 0.663 mmol), and the mixture was stirred at room temperaure for 15 hr. Then mixture was heated under reflux. After 6 hr at 70° C., the mixture was concentrated under reduced pressure. The crude residue was purified by column chromatography on a 40 g of Redi-Sep™ column using 0-100% gradient of EtOAc in Hexane over 14 min and then 100% isocratic of EtOAc for 10 min as eluent to give N4-((8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methyl)-5-fluoropyrimidine-2,4-diamine as a yellow syrup and the yellow syrup was purified by semi-prep-HPLC on a Gemini™ 10μ C18 column (250×21.2 mm, 10 μm) using 10-90% gradient of CH3CN (0.1% of TFA) in water (0.1% of TFA) over 28 min as eluent to give the desired product as a TFA salt. The purified product as a TFA salt was treated with saturated NaHCO3 (20 ml) and extracted with CH2Cl2 (30 ml×2). The combined organic layers were washed with H2O (30 ml×2), dried over Na2SO4, filtered, concentrated under reduced pressure to give N4-((8-chloro-2-(2-chlorophenyl)quinolin-3-yl)methyl)-5-fluoropyrimidine-2,4-diamine as a light yellow film: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.38 (1H, s), 8.07 (1H, dd, J=8.4, 1.2 Hz), 7.95 (1H, dd, J=7.5, 1.3 Hz), 7.48-7.67 (7H, m), 5.76 (2H, br. s.), 4.42 (2H, d, J=19.4 Hz); LC-MS (ESI) m/z 414.0 and 416.0 [M+H]+.

1. temperatureThen mixture was heated
2. temperatureunder reflux
3. waitAfter 6 hr at 70° C.
4. concentrationthe mixture was concentrated under reduced pressure
5. customThe crude residue was purified by column chromatography on a 40 g of Redi-Sep™ column
6. customover 14 min