SME-308, SLV-308
盐酸帕多芦诺 帕多芦诺 Chemical Name: 7-(4-Methyl-1-piperazinyl)benzoxazol-2(3H)-one monohydrochloride
CAS No. 269718-83-4, 269718-84-5 (free base)
项目整合开发状态: Phase II
项目研究机构: Solvay (Originator), Meiji Seika (Codevelopment)
合成路线:The synthesis of SLV308 was obtained as follows: The first step is the reduction of just one nitro group,which was accomplished by treating 2,6-dinitrophenol (I) with sodium sulfide in the presence of sodium hydrogencarbonate dissolved in a water/MeOH mixture to yield 2-amino-6-nitro-phenol (II) in 62%.To construct the heterocyclic ring,(II) was reacted with carbonyldiimidazole in dry tetrahydrofuran to give the nitro benzoxazolinone (III) almost quantitatively.The reduction of the nitro group of (III) was performed in acetone/Raney-Ni,resulting in the corresponding aniline (IV) (72%).Transforming the aniline (IV) into the piperazine was done by heating (IV) and bis(2-chloroethyl)amine in chlorobenzene at reflux temperature; after 70 hours the desired piperazine (V) was obtained after chromatographic purification in 60% yield.The last step,introduction of the methyl group,was achieved by a reductive amination; formaldehyde,sodium triacetoxyborohydride and triethylamine dissolved in dichloroethane were added to (V).After work-up,chromatographic purification and subsequent treatment with ethanolic HCl,SLV308 was isolated in 81% yield.
📌 参考资料/链接：
参考文献标题:New piperazine and piperidine cpds.
文献作者:Feenstra,R.W.; Visser,G.M.; Van der Heijden,J.A.M.; Long,S.K.; Toorop,G.P.; Van Scharrenburg,G.J.M.; Kruse,C.G.; Mos,J.; Toorop,A.G.(Duphar International Research BV)
参考来源:WO 0029397
📄 详细内容
合成路线:The synthesis of SLV308 was obtained as follows: The first step is the reduction of just one nitro group,which was accomplished by treating 2,6-dinitrophenol (I) with sodium sulfide in the presence of sodium hydrogencarbonate dissolved in a water/MeOH mixture to yield 2-amino-6-nitro-phenol (II) in 62%.To construct the heterocyclic ring,(II) was reacted with carbonyldiimidazole in dry tetrahydrofuran to give the nitro benzoxazolinone (III) almost quantitatively.The reduction of the nitro group of (III) was performed in acetone/Raney-Ni,resulting in the corresponding aniline (IV) (72%).Transforming the aniline (IV) into the piperazine was done by heating (IV) and bis(2-chloroethyl)amine in chlorobenzene at reflux temperature; after 70 hours the desired piperazine (V) was obtained after chromatographic purification in 60% yield.The last step,introduction of the methyl group,was achieved by a reductive amination; formaldehyde,sodium triacetoxyborohydride and triethylamine dissolved in dichloroethane were added to (V).After work-up,chromatographic purification and subsequent treatment with ethanolic HCl,SLV308 was isolated in 81% yield.
参考文献标题:SLV308
文献作者:van Scharrenburg,G.; Feenstra,R.; Long,S.; Koopman,T.; Stoker,M.; de Vries,M.; Ronken,E.; van Charldorp,K.; McCreary,A.
参考来源:Drugs Fut 2001,26(2),128
产品链接: CAS No. 269718-83-4›› 产品链接: CAS No.269718-84-5››