Ritanserin, R-55667, Tiserton
利坦丝林Chemical Name: 6-[2-[4-[Bis(p-fluorophenyl)methylene]piperidino]ethyl]-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
CAS No. 87051-43-2
项目整合开发状态: Phase III
项目研究机构: Janssen (Originator)
合成路线:The Grignard condensation of ethyl 1-benzyl-piperidine-4-carboxylate (I) with 4-fluorophenylmagnesium bromide (II) in THF gives a-bis(4-fluorophenyl)-1-benzylpiperidine-4-methanol (III),which is dehydrated with HCl in refluxing acetic acid yielding 1-benzyl-4-[bis(4 fluorophenyl)methylene]piperidine (IV).Elimination of the benzyl group of (IV) by hydrogenation with H2 over rhodium/carbon in methanol affords 4-[bis(4 fluorophenyl)metlylene] piperidine (V),which is finally condensed with 6-(2-chloroethyl)-7-methyl 5H thiazolo[3,2-a]pyrimidin-5-one (VI) by means of Na2CO3 and KI lo refluxing 4-methyl-2-pentanone.Compound (VI) is obtained by cyclocondensation of 2-thiazolylamine (VII) with 3 acetyl 4,5 dihydro-2(3H)furanone (VIII) by means of aqueous concentrated HCl in refluxing toluene.
📌 参考资料/链接：
参考文献标题:Novel ((bis(aryl)methylene)-1-piperidinyl)alkyl-pyrimidinones
文献作者:Kennis,L.E.J.; Mertens,J.C.; Vandenberk,J.(Janssen Pharmaceutica NV)
参考来源:EP 0110435; ES 8601965; US 4485107
📄 详细内容
合成路线:The Grignard condensation of ethyl 1-benzyl-piperidine-4-carboxylate (I) with 4-fluorophenylmagnesium bromide (II) in THF gives a-bis(4-fluorophenyl)-1-benzylpiperidine-4-methanol (III),which is dehydrated with HCl in refluxing acetic acid yielding 1-benzyl-4-[bis(4 fluorophenyl)methylene]piperidine (IV).Elimination of the benzyl group of (IV) by hydrogenation with H2 over rhodium/carbon in methanol affords 4-[bis(4 fluorophenyl)metlylene] piperidine (V),which is finally condensed with 6-(2-chloroethyl)-7-methyl 5H thiazolo[3,2-a]pyrimidin-5-one (VI) by means of Na2CO3 and KI lo refluxing 4-methyl-2-pentanone.Compound (VI) is obtained by cyclocondensation of 2-thiazolylamine (VII) with 3 acetyl 4,5 dihydro-2(3H)furanone (VIII) by means of aqueous concentrated HCl in refluxing toluene.
参考文献标题:Ritanserin
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1986,11(5),391
产品链接: CAS No. 87051-43-2››