2-氨基-5-溴-3-吗啉-4-基吡嗪的合成

Synthesis of 2-Amino-5-bromo-3-morpholin-4-ylpyrazine

以2-氨基吡嗪(Ⅰ)为原料,经溴代、吗啉取代,合成得到目标化合物2-氨基-5-溴-3-吗啉-4-基吡嗪(Ⅲ),合成路线总收率为45.9%(以2-氨基吡嗪计),目标化合物结构经1HNMR确证。该文对反应投料比、温度、反应时间等因素进行了考察并优化,最优反应条件为:n(2-氨基吡嗪)∶n(溴素)∶n(吡啶)=1∶2.1∶2.1,避光,40℃下反应30 min;每克3,5-二溴-2-氨基吡嗪加入4 mL吗啉,80℃下反应1 h。优化后的合成路线反应条件温和、操作简单、成本低廉,适合较大规模制备。

2-Amino-5-bromo-3-morpholin-4-ylpyrazine was prepared from 2-amidopyrazine in an overall yield of 45.9% via bromination and substitution by morpholine, and its structure was confirmed by ^1HNMR. The reaction conditions were optimized in terms of temperature, reactant proportions, and reaction time. The optimized reaction conditions are as follows ： n （ 2-amidopyrazine ） ： n （ bromine ） ： n （pyridine） = 1：2. 1：2. 1, the reaction being conducted at 40 ~C for 30 rain,and kept in dark place;4 rnL morpholine was added per gram of 3,5-dibromopyrazin-2-amine, the reaction being conducted at 80℃ for an hour. The improved process has the advantages of mild reaction conditions, simple operation, and low cost, which is also suitable for large scale synthesis.