Guo Lei-ming
2012
Citations
0
Influential Citations
2
Citations
Journal
Anhui Chemical Industry
Abstract
4,6-Dichloro-2-methylpyrimidine is an important intermediate of synthetic anticancer drug dasatinib.4,6-dichloro-2-methylpyrimidine was synthesized from acetamidine 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)=1∶3.4,in methanol at 20℃ 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℃ for 4h,the yield of 4,6-dichloro-2-methylpyrimidine was 69.55%,the yield of two-steps was 59.65%.