摘要
4,6-二氯-2-甲基嘧啶是合成抗癌药物达沙替尼的重要中间体。以乙脒盐酸盐和丙二酸二甲酯为原料经过环化、三氯氧磷氯化合成4,6-二氯-2-甲基嘧啶。正交试验确定合成4,6-二羟基-2-甲基嘧啶的较优工艺条件为:以甲醇为溶剂,n(乙脒盐酸盐)/n(甲醇钠)=1∶3.4,温度20℃下反应4 h,收率85.76%;正交试验确定三氯氧磷氯化的较优工艺条件为:以三氯氧磷为溶剂和氯化试剂,反应温度105℃,N,N-二乙基苯胺用量为4,6-二羟基-2-甲基嘧啶物质的量的2倍下反应4 h,收率69.55%;两步总收率59.65%。
4, 6-Dichloro-2-methylpyrimidine is an important intermediate of synthetic anticancer drug dasahmb. 4, o- diehloro-2-methylpyrimidine was synthesized from aeetamidine hydrochloride and dimethyl malonate via the cyclization and chlorination with phosphorus oxychloride. The optimal conditions of synthesis of 4, 6-dihydroxy-2-methylpyrimidine were investigated by orthogonal test. They were： n（acetamidine hydrochloride）/n（sodium methoxide）=l ： 3.4, in methanol at 20~C for 4h, the yield of 4, 6-dihydroxy-2-methylpyrimidine was 85.76%. The optimal conditions of chlorination with phosphorus oxychloride were investigated by orthogonal test. They were： n（N, N-diethyl-Benzenamine）/n（4,6-dihydroxy- 2-methylpyrimidine）=2 ： 1, in phosphorus oxychloride at 105~C for 4h, the yield of 4, 6-dichloro-2-methylpyrimidine was 69.55%, the yield of two-steps was 59.65%.
出处
《安徽化工》
CAS
2012年第4期34-37,共4页
Anhui Chemical Industry
