8-Hydroxycarteolol

合成路线:The nitration of 8-hydroxy-3,4-dihydrocarbostyril (I) with HNO3 in acetic acid-acetic anhydride gives 5-nitro-8-hydroxy-3,4-dihydrocarbostyril (II),which is reduced with SnCl2 in concentrated HCl yielding 5-amino-8-hydroxy-3,4-dihydrocarbostyril (III).The oxidation of (III) with FeCl3 in aqueous HCl affords 5,8-dioxo-3,4,5,8-tetrahydrocarbostyril (IV),which by treatment with SO2 in water is converted into 5,8-dihydroxy-3,4-dihydrocarbostyril (V).The treatment of (V) with benzyl chloride (A) and potassium carbonate in acetone gives 5-hydroxy-8-benzyloxy-3,4-dihydrocarbostyril (VII),which by reaction with epichlorohydrin (B) by means of piperidine affords 8-benzyloxy-5-(2,3-epoxypropoxy)-3,4-dihydrocarbostyril (VII).The opening of the epoxide ring of (VII) with tert-butylamine (C) in methanol yields 8-benzyloxy-5-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydrocarbostyril (VIII) (1,2),which is finally hydrogenated with H2 over Pd/C.

合成路线:The diketone (IV) can also be obtained as follows: the nitration of 5-hydroxy-3,4-dihydrocarbostyril (IX) with HNO3 in acetic acid - acetic anhydride gives 5-hydroxy-8-nitro-3,4-dihydrocarbostyril (X),which is reduced with H2 over Pd/C affording 5-hydroxy-8-amino-3,4-dihydrocarbostyril (Xl).Finally,this compound is oxidized with FeCl3 in aqueous HCl.

合成路线:The dihydroxy compound (V) can also be obtained as follows: the nitration of 8-hydroxycarbostyril (XII) with HNO3 in acetic acid-acetic anhydride gives 5-nitro-8-hydroxycarbostyril (XIII),which is reduced with SnCl2 yielding 5-amino-8-hydroxycarbostyril (XIV).The oxidation of (XIV) with FeCl3 affords 5,8-dioxo-5,8-dihydrocarbostyril (XV),which is reduced with SO2 giving 5,8-dihydroxycarbostyril (XVI).Finally,this compound is reduced with H2 over Pd/C.The 5-amino-8-hydroxy compound (XIV) can also be obtained by nitrosation of (XII) with NaNO2 in acetic acid acetic anhydride to give 5-nitroso-8-acetoxycarbostyril (XVII),which is then reduced with SnCl2 in concentrated HCl.

参考文献标题:Synthesis of 5-(3-tert-butylamino-2-hydroxypropxy)-8-3,4-dihydrocarbostyril hydochloride and its beta-adrenergic blocking agent
文献作者:Uchida,M.; et al.
参考来源:Yakugaku Zasshi 1976,96(5),571-577


合成路线:The nitration of 8-hydroxy-3,4-dihydrocarbostyril (I) with HNO3 in acetic acid-acetic anhydride gives 5-nitro-8-hydroxy-3,4-dihydrocarbostyril (II),which is reduced with SnCl2 in concentrated HCl yielding 5-amino-8-hydroxy-3,4-dihydrocarbostyril (III).The oxidation of (III) with FeCl3 in aqueous HCl affords 5,8-dioxo-3,4,5,8-tetrahydrocarbostyril (IV),which by treatment with SO2 in water is converted into 5,8-dihydroxy-3,4-dihydrocarbostyril (V).The treatment of (V) with benzyl chloride (A) and potassium carbonate in acetone gives 5-hydroxy-8-benzyloxy-3,4-dihydrocarbostyril (VII),which by reaction with epichlorohydrin (B) by means of piperidine affords 8-benzyloxy-5-(2,3-epoxypropoxy)-3,4-dihydrocarbostyril (VII).The opening of the epoxide ring of (VII) with tert-butylamine (C) in methanol yields 8-benzyloxy-5-(3-tert-butylamino-2-hydroxypropoxy)-3,4-dihydrocarbostyril (VIII) (1,2),which is finally hydrogenated with H2 over Pd/C.

合成路线:The diketone (IV) can also be obtained as follows: the nitration of 5-hydroxy-3,4-dihydrocarbostyril (IX) with HNO3 in acetic acid - acetic anhydride gives 5-hydroxy-8-nitro-3,4-dihydrocarbostyril (X),which is reduced with H2 over Pd/C affording 5-hydroxy-8-amino-3,4-dihydrocarbostyril (Xl).Finally,this compound is oxidized with FeCl3 in aqueous HCl.

合成路线:The dihydroxy compound (V) can also be obtained as follows: the nitration of 8-hydroxycarbostyril (XII) with HNO3 in acetic acid-acetic anhydride gives 5-nitro-8-hydroxycarbostyril (XIII),which is reduced with SnCl2 yielding 5-amino-8-hydroxycarbostyril (XIV).The oxidation of (XIV) with FeCl3 affords 5,8-dioxo-5,8-dihydrocarbostyril (XV),which is reduced with SO2 giving 5,8-dihydroxycarbostyril (XVI).Finally,this compound is reduced with H2 over Pd/C.The 5-amino-8-hydroxy compound (XIV) can also be obtained by nitrosation of (XII) with NaNO2 in acetic acid acetic anhydride to give 5-nitroso-8-acetoxycarbostyril (XVII),which is then reduced with SnCl2 in concentrated HCl.
参考文献标题:8-Hydroxycarteolol
文献作者:Casta馿r,J.; Blancafort,P.; Serradell,M.N.
参考来源:Drugs Fut 1980,5(2),78