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Azalanstat dihydrochloride, Azalanstat hydrochloride, RS-21607-197

苯甲胺,4-[[[(2S,4S)-2-[2-(4-氯苯基)乙基]-2-(1H-吡唑-1-甲基)-1,3-二氧鐺-4-基]甲基硫]-盐酸盐(1:2) 阿扎兰司他 Chemical Name: (2S,4S)-4-(4-Aminophenylsulfanylmethyl)-2-[2-(4-chlorophenyl)ethyl]-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane dihydrochloride
CAS No. 143484-82-6, 143393-27-5 (free base), 143326-80-1 (racemic free base)
项目整合开发状态: Phase II
项目研究机构: Roche Bioscience (Originator)
合成路线:Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III),which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV).Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI),which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII).Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers,and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization.Finally,(IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.
📌 参考资料/链接:
参考文献标题:1,3-Dioxolane derivs.as cholesterol lowering agents
文献作者:Walker,K.A.; Burton,P.M.; Swinney,D.C.(Syntex (USA),Inc.)
参考来源:JP 1992308588; US 5158949

📄 详细内容


合成路线:Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III),which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV).Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI),which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII).Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers,and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization.Finally,(IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

参考文献标题:Process for preparing 1,3-dioxolane derivs
文献作者:Dyson,N.H.; Gardner,J.O.; Prince,A.; Kertesz,D.J.(Syntex (USA),Inc.)
参考来源:JP 1995508002; US 5208331


合成路线:Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III),which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV).Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI),which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII).Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers,and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization.Finally,(IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

参考文献标题:RS-21607-197
文献作者:Prous,J.; Mealy,N.; Castar,J.
参考来源:Drugs Fut 1994,19(2),125


合成路线:Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III),which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV).Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI),which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII).Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers,and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization.Finally,(IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.
参考文献标题:Selective inhibition of mammalian lanosterol 14alpha-demethylase: A possible strategy for cholesterol lowering
文献作者:Walker,K.A.M.; Kertesz,D.J.; Rotstein,D.M.; Swinney,D.C.; Berry,P.W.; So,O.Y.; Webb,A.S.; Watson,D.M.; Mak,A.Y.; Burton,P.M.; et al.
参考来源:J Med Chem 1993,36(15),2235-7


产品链接: CAS No. 143484-82-6››

产品链接: CAS No.143393-27-5››