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.
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.
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.