Mafoprazine mesylate, IK-640, Mafoprane
马福拉嗪Chemical Name: 1-[3-(4-Acetamido-2-methoxyphenoxy)propyl]-4-(2-fluorophenyl)piperazine methanesulfonate
CAS No. 80428-29-1 (free base)
项目整合开发状态: Phase I
项目研究机构: Sumitomo Pharmaceuticals (Originator), Tanabe Seiyaku (Originator)
合成路线:By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II).The starting products are obtained as follows:a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V),which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I).b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII),which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX).The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI),which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).
📌 参考资料/链接：
参考文献标题:N-Aryl-N-phenoxy-alkyl-piperazine compounds useful in decreasing intracranial presssure
文献作者:Kanno,T.; Gaino,M.; Yamamura,M.; Ishida,R.; Shintomi,K.(Tanabe Seiyaku Co.,Ltd.)
参考来源:EP 0034284; JP 156115769; US 4413006
📄 详细内容
合成路线:By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II).The starting products are obtained as follows:a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V),which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I).b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII),which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX).The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI),which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).
参考文献标题:Mafoprazine mesylate
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1988,13(10),920
合成路线:By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II).The starting products are obtained as follows:a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V),which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I).b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII),which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX).The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI),which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).
参考文献标题:Neurochemical study of mafoprazine,a new phenylpiperazine derivative
文献作者:Fukuchi,I.; et al.
参考来源:Jpn Pharmacol 1988,47(9),51
产品链接: CAS No. 80428-29-1››