合成路线:Nucleophilic aromatic substitution of 2-chloro-3-nitropyridine (II) with excess piperazine (I) in acetonitrile at room temperature produces 1-(3-nitro-2-pyridyl)piperazine.Protection of the free piperazine nitrogen by treatment with di-tert-butyldicarbonate affords nitropyridine (III).Reduction of the nitro group to the amine is accomplished via hydrogenation (40 psi) over palladium on carbon.Treatment of the aminopyridine with acetaldehyde and sodium cyanoborohydride in methanol affords the (ethylamino)pyridine (IV).Removal of the BOC protecting group with trifluoroacetic acid and coupling of the resulting 1-[3-(ethylamino)pyridyl]piperazine with 5-methoxyindole-2-carboxylic acid using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) or 1,1'-carbonyldiimidazole (CDI) affords U-87201 (V).Dissolution of (V) in methanol,treatment with 1 eq of methanesulfonic acid,and the addition of diethyl ether results in the precipitation of atevirdine mesylate.
合成路线:The synthesis of delavirdine mesylate is depicted in Scheme 19654001a:The first three chemical steps are the same as those used for the synthesis of atevirdine mesylate (ATV,U-87201E) (2,3).Nucleophilic aromatic substitution of 2-chloro-3-nitropyridine (II) with excess piperazine in acetonitrile at room temperature produces 1-(3-nitro-2-pyridyl)piperazine.Protection of the free piperazine nitrogen by treatment with di-tert-butyldicarbonate affords nitropyridine (III).Reduction of the nitro group to the amine is accomplished via hydrogenation (40 psi) over palladium on carbon.Treatment of the aminopyridine with acetone and sodium cyanoborohydride in methanol affords the 3-(1-methylethylamino)pyridine (IV).Removal of the BOC protecting group with trifluoroacetic acid and coupling of the resulting 1-[3-(1-methylethylamino)pyridyl]piperazine with 5-nitroindole-2-carboxylic acid using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) or 1,1'-carbonyldiimidazole (CDI) affords (V).Catalytic reduction of the nitro group and treatment of the resulting amine with methanesulfonyl chloride provides U-90152.Dissolution of U-90152 in acetonitrile and treatment with 1 eq of methanesulfonic acid results in the precipitation of delavirdine mesylate.
参考文献标题:Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication
文献作者:Romero,D.L.; Busso,M.; Tan,C.-K.; Reusser,F.; Palmer,J.R.; Poppe,S.M.; Aristoff,P.A.; Downey,K.M.; So,A.G.; Resnick,L.; et al.
参考来源:Proc Natl Acad Sci USA 1991,88(19),8806-10
合成路线:The synthesis of delavirdine mesylate is depicted in Scheme 19654001a:The first three chemical steps are the same as those used for the synthesis of atevirdine mesylate (ATV,U-87201E) (2,3).Nucleophilic aromatic substitution of 2-chloro-3-nitropyridine (II) with excess piperazine in acetonitrile at room temperature produces 1-(3-nitro-2-pyridyl)piperazine.Protection of the free piperazine nitrogen by treatment with di-tert-butyldicarbonate affords nitropyridine (III).Reduction of the nitro group to the amine is accomplished via hydrogenation (40 psi) over palladium on carbon.Treatment of the aminopyridine with acetone and sodium cyanoborohydride in methanol affords the 3-(1-methylethylamino)pyridine (IV).Removal of the BOC protecting group with trifluoroacetic acid and coupling of the resulting 1-[3-(1-methylethylamino)pyridyl]piperazine with 5-nitroindole-2-carboxylic acid using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) or 1,1'-carbonyldiimidazole (CDI) affords (V).Catalytic reduction of the nitro group and treatment of the resulting amine with methanesulfonyl chloride provides U-90152.Dissolution of U-90152 in acetonitrile and treatment with 1 eq of methanesulfonic acid results in the precipitation of delavirdine mesylate.
参考文献标题:Bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: Structure-activity relationships of novel substituted indole analogues and the identification oF (U-90152S),a second-generation clinical candidate
文献作者:Romero,D.L.; Morge,R.A.; Genin,M.J.; Biles,C.; Busso,M.; Resnick,L.; Althaus,I.W.; Reusser,F.; Thomas,R.C.; Tarpley,W.G.
参考来源:J Med Chem 1993,36(10),1505-8
合成路线:The synthesis of delavirdine mesylate is depicted in Scheme 19654001a:The first three chemical steps are the same as those used for the synthesis of atevirdine mesylate (ATV,U-87201E) (2,3).Nucleophilic aromatic substitution of 2-chloro-3-nitropyridine (II) with excess piperazine in acetonitrile at room temperature produces 1-(3-nitro-2-pyridyl)piperazine.Protection of the free piperazine nitrogen by treatment with di-tert-butyldicarbonate affords nitropyridine (III).Reduction of the nitro group to the amine is accomplished via hydrogenation (40 psi) over palladium on carbon.Treatment of the aminopyridine with acetone and sodium cyanoborohydride in methanol affords the 3-(1-methylethylamino)pyridine (IV).Removal of the BOC protecting group with trifluoroacetic acid and coupling of the resulting 1-[3-(1-methylethylamino)pyridyl]piperazine with 5-nitroindole-2-carboxylic acid using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) or 1,1'-carbonyldiimidazole (CDI) affords (V).Catalytic reduction of the nitro group and treatment of the resulting amine with methanesulfonyl chloride provides U-90152.Dissolution of U-90152 in acetonitrile and treatment with 1 eq of methanesulfonic acid results in the precipitation of delavirdine mesylate.
参考文献标题:Delavirdine Mesylate
文献作者:Romero,D.L.
参考来源:Drugs Fut 1994,19(3),238
合成路线:The synthesis of delavirdine mesylate is depicted in Scheme 19654001a:The first three chemical steps are the same as those used for the synthesis of atevirdine mesylate (ATV,U-87201E) (2,3).Nucleophilic aromatic substitution of 2-chloro-3-nitropyridine (II) with excess piperazine in acetonitrile at room temperature produces 1-(3-nitro-2-pyridyl)piperazine.Protection of the free piperazine nitrogen by treatment with di-tert-butyldicarbonate affords nitropyridine (III).Reduction of the nitro group to the amine is accomplished via hydrogenation (40 psi) over palladium on carbon.Treatment of the aminopyridine with acetone and sodium cyanoborohydride in methanol affords the 3-(1-methylethylamino)pyridine (IV).Removal of the BOC protecting group with trifluoroacetic acid and coupling of the resulting 1-[3-(1-methylethylamino)pyridyl]piperazine with 5-nitroindole-2-carboxylic acid using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) or 1,1'-carbonyldiimidazole (CDI) affords (V).Catalytic reduction of the nitro group and treatment of the resulting amine with methanesulfonyl chloride provides U-90152.Dissolution of U-90152 in acetonitrile and treatment with 1 eq of methanesulfonic acid results in the precipitation of delavirdine mesylate.
参考文献标题:Atevirdine mesylate (U-87201E)
文献作者:Romero,D.L.
参考来源:Drugs Fut 1994,19(1),7-12
产品链接: CAS No. 148692-47-1›› 产品链接: CAS No.136817-59-9››