在這種合成嘧啶環(huán)的方法中，必須要嚴(yán)格的控制無水無氧條件，溫度的控制也很嚴(yán)格；Tf₂O和2-ClPyr加入的當(dāng)量數(shù)對反應(yīng)的收率影響不小，2-ClPy作為base，加入1.2個當(dāng)量時反應(yīng)的產(chǎn)率是最高的。在同樣的條件下，用其他的base (如：TEA,DIPEA or pyridine)都沒有用2-ClPyr作為base的產(chǎn)率高。

反應(yīng)實例：

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.