Nifekalant hydrochloride, MS-551, Shinbit
盐酸奈非卡那特(MS-551) 尼非卡兰 Chemical Name: 6-[2-[N-(2-Hydroxyethyl)-3-(4-nitrophenyl)propylamino]ethylamino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione hydrochloride
CAS No. 130656-51-8, 130636-43-0 (free base)
项目整合开发状态: Launched-1999
项目研究机构: Mitsui Pharmaceuticals (Originator), Mitsui Chemicals (Bulk Supplier)
合成路线:By condensation of N-(2-hydroxyethyl)-N-[3-(4-nitrophenyl)propyl]amine (I) with 1,3-dimethyl-6-[2-(p-toluenesulfonyloxy)ethylamino]pyrimidine-2,4(1H,3H)-dione (II) by means of NaOH in hot ethanol or methanol.The starting materials are obtained as follows:1) The esterification of 3-(4-nitrophenyl)propanol (III) with p-toluenesulfonyl chloride (IV) by means of pyridine in chloroform gives the corresponding p-toluenesulfonate (V),which is then condensed with ethanolamine (VI) by heating at 100 C to afford amine (I).2) The condensation of ethanolamine (VI) with 6-chloro-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VII) by heating at 90 C,or by means of triethylamine in refluxing isopropanol,gives 6-(2-hydroxyethylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VIII),which is then esterified with p-toluenesulfonyl chloride (IV) as before yielding pyrimidine (II).
📌 参考资料/链接：
参考文献标题:Pyrimidinedione deriv.cpds.,method of producing the same and antiarrhythmic agents containing the same
文献作者:Katakami,T.; Yokoyama,T.; Miyamoto,M.; Mori,H.; Kawauchi,N.; Nobori,T.; Sannohe,K.; Kamiya,J.; Ishii,M.; Yoshihara,K.(Mitsui Chemicals,Inc.)
参考来源:AU 8943869; EP 0369627; JP 1991112948; JP 1991173873; US 5008267
📄 详细内容
合成路线:By condensation of N-(2-hydroxyethyl)-N-[3-(4-nitrophenyl)propyl]amine (I) with 1,3-dimethyl-6-[2-(p-toluenesulfonyloxy)ethylamino]pyrimidine-2,4(1H,3H)-dione (II) by means of NaOH in hot ethanol or methanol.The starting materials are obtained as follows:1) The esterification of 3-(4-nitrophenyl)propanol (III) with p-toluenesulfonyl chloride (IV) by means of pyridine in chloroform gives the corresponding p-toluenesulfonate (V),which is then condensed with ethanolamine (VI) by heating at 100 C to afford amine (I).2) The condensation of ethanolamine (VI) with 6-chloro-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VII) by heating at 90 C,or by means of triethylamine in refluxing isopropanol,gives 6-(2-hydroxyethylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VIII),which is then esterified with p-toluenesulfonyl chloride (IV) as before yielding pyrimidine (II).
参考文献标题:MS-551
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1993,18(3),226
合成路线:By condensation of N-(2-hydroxyethyl)-N-[3-(4-nitrophenyl)propyl]amine (I) with 1,3-dimethyl-6-[2-(p-toluenesulfonyloxy)ethylamino]pyrimidine-2,4(1H,3H)-dione (II) by means of NaOH in hot ethanol or methanol.The starting materials are obtained as follows:1) The esterification of 3-(4-nitrophenyl)propanol (III) with p-toluenesulfonyl chloride (IV) by means of pyridine in chloroform gives the corresponding p-toluenesulfonate (V),which is then condensed with ethanolamine (VI) by heating at 100 C to afford amine (I).2) The condensation of ethanolamine (VI) with 6-chloro-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VII) by heating at 90 C,or by means of triethylamine in refluxing isopropanol,gives 6-(2-hydroxyethylamino)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (VIII),which is then esterified with p-toluenesulfonyl chloride (IV) as before yielding pyrimidine (II).
参考文献标题:Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H) pyrimidinediones,novel class III antiarrhythmic agents
文献作者:Katakami,T.; Yokoyama,T.; Miyamoto,M.; Mori,H.; Kawauchi,N.; Nobori,T.; San-nohe,K.; Kaiho,T.; Kamiya,J.
参考来源:J Med Chem 1992,35(18),3325-30
产品链接: CAS No. 130656-51-8›› 产品链接: CAS No.130636-43-0››