新产品编号:1019317
Chemical Name: 5-Methoxy-3-[1-methylpyrrolidin-2(R)-ylmethyl]-1H-indole
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:Alternatively,5-methoxyindole (III) was N-silylated employing tert-butyldimethylsilyl chloride and n-BuLi,and the resulting silyl derivative (V) was brominated with N-bromosuccinimide at -78 C to afford the 3-bromoindole (VI).After lithium-bromine exchange in (VI) with n-BuLi at -78 C,the 3-lithio compound was condensed with N-methyl-D-proline methyl ester (VII) to give the indolyl ketone (VIII).The ketone function of (VIII) was finally reduced employing LiAlH4 in boiling THF.
合成路线:Silylation of 4-benzyloxyindole (I) employing tert-butyldimethylsilyl chloride and NaH gave the N-silyl derivative (II),which was brominated with N-bromosuccinimide at -78 C to afford the 3-bromoindole (III).After lithium-bromine exchange with n-BuLi at -78 C,the 3-lithio compound was condensed with N-methyl-D-proline methyl ester (IV) to give the indolyl ketone (V).The ketone function of (V) was finally reduced employing LiAlH4 in boiling dioxan,with concomitant cleavage of the benzyl ether to furnish the title compound.
📌 参考资料/链接：
参考文献标题:Further studies on oxygenated tryptamines with LSD-like activity incorporating a chiral pyrrolidine moiety into the side chain
文献作者:Gerasimov,M.; Marona-Lewicka,D.; Kurrasch-Orbaugh,D.M.; Qandil,A.M.; Nichols,D.E.
参考来源:J Med Chem 1999,42(20),4257
📄 详细内容
合成路线:The title compound has been prepared by two related procedures.Treatment of N-carbobenzoxy-D-proline (I) with oxalyl chloride provided the corresponding acid chloride (II).This was condensed with 5-methoxyindolyl magnesium bromide,generated from 5-methoxyindole (III) and ethylmagnesium bromide,to afford the indolyl ketone (IV).Reduction of both keto and carbamate groups of (IV) by means of LiAlH4 in refluxing THF then furnished the target compound.
参考文献标题:Synthesis and serotonergic pharmacology of the enantiomers of 3-[(N-methylpyrrolidin-2-yl)methyl]-5-methoxy-1H-indole: Discovery of stereogenic differentiation in the aminoethyl side chain of the neurotransmitter serotonin
文献作者:Macor,J.E.; Blake,J.; Fox,C.B.; Johnson,C.; Koe,B.K.; Lebel,L.A.; Morrone,J.M.; Ryan,K.; Schmidt,A.W.; Schulz,D.W.; et al.
参考来源:J Med Chem 1992,35(23),4503