Réaction #607450

Équation de réaction

anthranilic acid hydrochloride

methazonic acid

potassium acetate

→

3-nitro-4-hydroxyquinoline

Solvants

2-β-nitroethylideneaminobenzoic acid

acetic anhydride

Conditions de réaction

Traitement

1. 1
   Autrewere synthesized

Mode opératoire

In general, the novel derivatives 31-47 were synthesized as shown in the scheme depicted in FIG. 1. Condensation of anthranilic acid hydrochloride (1) with methazonic acid (2) resulted in 2-β-nitroethylideneaminobenzoic acid (3), which was dehydrated in acetic anhydride in the presence of potassium acetate to give 3-nitro-4-hydroxyquinoline (5) [Bachman, G. B. et al. Quinoline Derivatives from 3-Nitro-4-hydroxyquinoline, J. Am. Chem. Soc., 1947, 69, 365-371]. 3-Nitro-4-hydroxyquinoline (5) was treated with phosphorous oxychloride to afford 3-nitro-4-chloroquinoline (6). This was converted to 3-nitro-4-aminoquinoline (7) with ammonia, which was subsequently reduced by catalytic hydrogenation to 3,4-diaminoquinoline (8) with 10% palladium on charcoal as catalyst. The next step involved ring-closure, which was carried out in three different ways. For example, Compound 10 was prepared by ring closure of the appropriate carboxylic acid and 3,4-diaminoquinoline (8) in polyphosphoric acid [Young, R. C. et al. Purine Derivatives as Competitive Inhibitors of Human Erythrocyte Membrane Phosphatidylinositol 4-Kinase. J. Med. Chem. 1990, 33, 2073-2080]. Compound 14 was prepared by ring-closure of 2-furoyl chloride with 3,4-diaminoquinoline (8) [Scammells P. J. et al. Substituted 1,3-dipropylxanthines as irreversible antagonists of A1 adenosine receptors. J. Med. Chem. 1994, 37, 2704-2712]. Compound 9 was prepared by ring-closure of 3,4-diaminoquinoline (8) with formic acid in trimethylorthoformate. Oxidation with 3-chloroperoxybenzoic acid afforded 5-oxides 16-22, which subsequently could be converted with phosphorous oxychloride into the 4-chlorides 23-29. Finally, reaction with the appropriate amines afforded the desired compounds 30-47, respectively [Van Galen, P. J. M. et. al. 1-H-imidazo[4,5-c]quinolin-4-amines: Novel Non-Xanthine Adenosine Antagonists. J. Med. Chem. 1991, 34, 1202-1206].

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