2-丙硫基-4,6-二氯-5-氨基嘧啶的合成

Preparation of 2-Propylthio-4,6-dichloro-5-aminopyrimidine

丙二酸二乙酯、硫脲环合生成硫代巴比妥酸钠,在碘化四丁铵催化下经溴丙烷烷基化,再与30%～40%硝酸经管式硝化反应制得2-丙硫基-4,6-二羟基-5-硝基嘧啶,最后经氯代、还原合成了抗凝血药替卡格雷的重要中间体2-丙硫基-4,6-二氯-5-氨基嘧啶,总收率约67%。

2-Propylthio-4,6-dichloro-5-aminopyrimidine, the key intermediate of ticagrelor, was synthesized from diethyl malonate and thiourea by cyclization to give sodium 2-thiobarbiturate, followed by alkylation with bromopropane in presence of TBAI and nitration using 30% - 40% nitric acid in tubular reactor to afford 2-propylthio- 4,6-dihydroxy-5-nitropyrimidine, which was subjected to chlorination and reduction with an overall yield of 67 %.