A-259745
Chemical Name: 1-Methyl-5-[5-(3,4,5-trimethoxyphenyl)-4,5-dihydrooxazol-2-yl]-1H-indole
CAS No. 256934-83-5, 256935-04-3 (R-isomer), 256935-03-2 (S-isomer)
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:Condensation of 3,4,5-trimethoxybenzaldehyde (I) with nitromethane in the presence of KOH produced the nitro alcohol (II),which was subsequently hydrogenated over Pd/C to afford amino alcohol (III).Acylation of (III) with 5-indolecarboxylic acid (IV) gave the corresponding amide (V).Oxazoline (VI) was then obtained by cyclization of (V) in the presence of Burgess reagent.Finally,N-methylation of the indole ring with MeI and KOH furnished the title compound.
📌 参考资料/链接：
参考文献标题:Substd.oxazolines as antiproliferative agents
文献作者:Woods,K.W.; Wang,L.; Kalvin,D.M.; Barr,K.J.; Li,Q.; Liu,G.; Gwaltney,S.L.II; Claiborne,A.K.; Jae,H.-S.; Sham,H.L.(Abbott Laboratories Inc.)
参考来源:WO 0006556
📄 详细内容
合成路线:Condensation of 3,4,5-trimethoxybenzaldehyde (I) with nitromethane in the presence of KOH produced the nitro alcohol (II),which was subsequently hydrogenated over Pd/C to afford amino alcohol (III).Acylation of (III) with 5-indolecarboxylic acid (IV) gave the corresponding amide (V).Oxazoline (VI) was then obtained by cyclization of (V) in the presence of Burgess reagent.Finally,N-methylation of the indole ring with MeI and KOH furnished the title compound.
参考文献标题:Oxazoline antiproliferative agents
文献作者:Sham,H.L.; Jae,H.-S.; Li,Q.; Wang,L.; Woods,K.W.; Liu,G.; Barr,K.J.; Kalvin,D.M.; Gwaltney,S.L.II; Claiborne,A.K.(Abbott Laboratories Inc.)
参考来源:US 6228868
合成路线:In a closely related procedure,amino alcohol (III) was coupled with 1-methyl-5-indolecarboxylic acid (VII) to afford amide (VIII).This was then cyclized to the target oxazoline by using the Burgess reagent.
参考文献标题:Antimitotic agents with activity in multidrug-resistant tumor cell lines
文献作者:Sorensen,B.K.; Liu,G.; Tasker,A.S.; et al.
参考来源:221st ACS Natl Meet (April 1 2001,San Diego) 2001,Abst MEDI 139
合成路线:Condensation of 3,4,5-trimethoxybenzaldehyde (I) with nitromethane in the presence of KOH produced the nitro alcohol (II),which was subsequently hydrogenated over Pd/C to afford amino alcohol (III).Acylation of (III) with 5-indolecarboxylic acid (IV) gave the corresponding amide (V).Oxazoline (VI) was then obtained by cyclization of (V) in the presence of Burgess reagent.Finally,N-methylation of the indole ring with MeI and KOH furnished the title compound.
合成路线:In a closely related procedure,amino alcohol (III) was coupled with 1-methyl-5-indolecarboxylic acid (VII) to afford amide (VIII).This was then cyclized to the target oxazoline by using the Burgess reagent.
参考文献标题:New antimitotic agents with activity in multi-drug-resistant cell lines and in vivo efficacy in murine tumor models
文献作者:Szczepankiewicz,B.G.; Liu,G.; Jae,H.-S.; Tasker,A.S.; Gunawardana,I.W.; von Geldern,T.W.; Gwaltney,S.L.II; Wu-Wong,J.R.; Gehrke,L.; Chiou,W.J.; Credo,R.B.; Alder,J.D.; Nukkala,M.A.; Zielinski,N.A.; Jarvis,K.; Mollison,K.W.; et al.
参考来源:J Med Chem 2001,44(25),4416