ABT-518
N-[1(S)-[2,2-二甲基-1,3-二氧基-4(S)-基]-2-[4-[4-(三氟甲氧基)苯氧基]苯基磺酰]-N-羟基甲酰胺Chemical Name: N-[1(S)-[2,2-Dimethyl-1,3-dioxolan-4(S)-yl]-2-[4-[4-(trifluoromethoxy)phenoxy]phenylsulfonyl]ethyl]-N-hydroxyformamide
CAS No. 286845-00-9
项目整合开发状态: Phase I
项目研究机构: Abbott (Originator)
合成路线:The condensation of 4-(trifluoromethoxy)phenol (I) with 4-fluorophenyl(methyl)sulfone (II) by means of K2CO3 in hot DMSO gives the diphenyl ether (III),which is condensed with 2,2-dimethyl-1,3-dioxolane-(R)-carboxylic acid methyl ester (IV) by means of BuLi in THF to afford the ethanone (V).The reduction of (V) with NaBH4 in ethanol yields the ethanol derivative (VI),which is dehydrated to the ethylene (VII) by means of MsCl,TEA and NaHCO3.The addition of hydroxylamine to the double bond of (VII) provides the hydroxyamine derivative (VIII) as a diastereomeric mixture that is separated by flash chromatography,affording the desired enantiomer (IX).Finally,this compound is formylated by treatment with 2,2,2-trifluoroethyl formate (X) (obtained by reaction of 2,2,2-trifluoroethanol (XI) with hot formic acid (XII)) in refluxing MTBE.
📌 参考资料/链接：
参考文献标题:Reverse hydroxamate inhibitors of matrix metalloproteinases
文献作者:Curtin,M.L.; Davidsen,S.K.; Michaelides,M.R.; Steinman,D.H.; Dai,Y.; Heyman,H.R.; Holmes,J.H.(Abbott Laboratories Inc.)
参考来源:WO 0044739
📄 详细内容
合成路线:The condensation of 4-(trifluoromethoxy)phenol (I) with 4-fluorophenyl(methyl)sulfone (II) by means of K2CO3 in hot DMSO gives the diphenyl ether (III),which is condensed with 2,2-dimethyl-1,3-dioxolane-(R)-carboxylic acid methyl ester (IV) by means of BuLi in THF to afford the ethanone (V).The reduction of (V) with NaBH4 in ethanol yields the ethanol derivative (VI),which is dehydrated to the ethylene (VII) by means of MsCl,TEA and NaHCO3.The addition of hydroxylamine to the double bond of (VII) provides the hydroxyamine derivative (VIII) as a diastereomeric mixture that is separated by flash chromatography,affording the desired enantiomer (IX).Finally,this compound is formylated by treatment with 2,2,2-trifluoroethyl formate (X) (obtained by reaction of 2,2,2-trifluoroethanol (XI) with hot formic acid (XII)) in refluxing MTBE.
参考文献标题:Phenoxyphenyl sulfone N-forylhydroxylamines (retrohydroxamates) as potent,selective,orally bioavailable matrix metalloproteinase inhibitors
文献作者:Wada,C.K.; Holms,J.H.; Curtin,M.L.; Dai,Y.; Florjancic,A.S.; Garland,R.B.; Guo,Y.; Heyman,H.R.; Stacey,J.R.; Steinman,D.H.; Albert,D.H.; Bouska,J.J.; Elmore,I.N.; Goodfellow,C.L.; Marcotte,P.A.; Tapang,P.; Morgan,D.W.; et al.
参考来源:J Med Chem 2002,45(1),219
产品链接: CAS No. 286845-00-9››