▷ 合成取代嘧啶环的新方法

在这种合成嘧啶环的方法中，必须要严格的控制无水无氧条件，温度的控制也很严格；Tf2O和2-ClPyr加入的当量数对反应的收率影响不小，2-ClPy作为base，加入1.2个当量时反应的产率是最高的。在同样的条件下，用其他的base (如：TEA,DIPEA or pyridine)都没有用2-ClPyr作为base的产率高。

反应实例：

Experimental Section

Trifluoromethanesulfonic anhydride (1.10 equiv) was added via syringe over 2 min to a well-stirred mixtureof amide (1 equiv) and 2-chloropyridine(1.20 equiv) in dichloromethane (88 mL) at-78 ºC. After 10 min, the reaction mixture was placed in an ice-water bath and warmed to 0 ºC. After 4 min, nitrile (1.10 equiv) was added via syringe over 1 min.The resulting solution was allowed to warm to 23 ºC for 5 min before the reaction mixture was heated to 45 ºC in an oil bath. After 6 h, the reaction vessel was allowed to cool to 23 ºC and then triethylamine (8.08 mL) was introduced to neutralize thetrifluoromethanesulfonate salts. The volatiles were removed under reduced pressure and the residue was purified by flashcolumn chromatography (eluent: 10% EtOAc in hexanes; SiO2:11 6.5 cm) on neutralized silica gel to give quinazoline derivative product as a white solid.