SCH-57790
1-吡哌嗪乙腈,4-环己基-a-[4-[(S)-(4-甲氧基苯基)磺基]-Chemical Name: 2-(4-Cyclohexylpiperazin-1-yl)-2-[4-[(S)-4-methoxyphenylsulfinyl]phenyl]acetonitrile
CAS No. 221660-80-6, 182136-73-8 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Schering-Plough (Originator)
合成路线:Oxidation of disulfide (I) with sulfuryl chloride in AcOH at -20 C afforded (4-methoxyphenyl)sulfinyl chloride (II),which was condensed with (1R,2S)-2-phenylcyclohexanol to provide sulfinate (IV) as a single diastereomer.Subsequent condensation with the Grignard reagent (V) produced the chiral sulfoxide (VI).The diethyl acetal of (VI) was then hydrolyzed to the corresponding benzaldehyde (VII) using p-TsOH in THF-H2O.Finally,condensation of (VII) with N-cyclohexylpiperazine (VIII) using titanium tetraisopropoxide,followed by addition of diethylaluminum cyanide,furnished the target piperazinylacetonitrile.
📌 参考资料/链接：
参考文献标题:Benzylpiperidines and piperazines as muscarinic an
文献作者:Lowe,D.; Chang,W.; Kozlowski,J.; Berger,J.G.; McQuade,R.; Barnett,A.; Scherlock,M.; Tom,W.; Dugar,S.; Chen,L.-Y.; Clader,J.W.; Chackalamannil,S.(Schering Corp.)
参考来源:EP 0811002; JP 1999501014; US 5883096; WO 9626196
📄 详细内容
合成路线:Oxidation of disulfide (I) with sulfuryl chloride in AcOH at -20 C afforded (4-methoxyphenyl)sulfinyl chloride (II),which was condensed with (1R,2S)-2-phenylcyclohexanol to provide sulfinate (IV) as a single diastereomer.Subsequent condensation with the Grignard reagent (V) produced the chiral sulfoxide (VI).The diethyl acetal of (VI) was then hydrolyzed to the corresponding benzaldehyde (VII) using p-TsOH in THF-H2O.Finally,condensation of (VII) with N-cyclohexylpiperazine (VIII) using titanium tetraisopropoxide,followed by addition of diethylaluminum cyanide,furnished the target piperazinylacetonitrile.
参考文献标题:Diphenyl sulfoxides as selective antagonists of the muscarinic M2 receptor
文献作者:Kozlowski,J.A.; Lowe,D.B.; Guzik,H.S.; Zhou,G.; Ruperto,V.B.; Duffy,R.A.; McQuade,R.; Crosby,G.; Taylor,L.A.; Billard,W.; Binch,H.III.; Lachowicz,J.E.
参考来源:Bioorg Med Chem Lett 2000,10(20),2255
产品链接: CAS No. 221660-80-6››