3-Nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine (III) was prepared by heating tetrahydropyranone (I) with dinitropyridone (II) in methanolic ammonia following a reported procedure. Hydrogenation of the nitro derivative (III) and protection of the resulting amine (IV) with trichloroacetyl chloride afforded the trichloroacetamide (V). Oxidation of the pyridine ring of (V) with 3-chloroperoxybenzoic acid gave the N-oxide (VI). Nitration of the pyridine ring of (VI) with fuming nitric acid, followed by amide hydrolysis with ammonium hydroxide provided the 3-amino-4-nitropyridine N-oxide (VII). Reduction of the N-oxide and 4-nitro groups of (VII) was accomplished in a single step by hydrogenation in the presence of Raney-nickel to furnish the bicyclic diaminopyridine (VIII). Subsequent monoacylation of (VIII) with isoxazole-3-carbonyl chloride (IX) followed by thermal cyclization provided the desired imidazopyranopyridine compound (1,2), which was finally isolated as the title phosphate salt

In a related procedure, the pyranopyridine (III) was oxidized to the corresponding N-oxide (X) with 3-chloroperoxybenzoic acid, and the nitro group of (X) was subsequently reduced to amine (XI) by catalytic hydrogenation over Pd/C. Acylation of (XI) with isoxazole-3-carbonyl chloride (IX) provided amide (XII). After pyridine ring nitration with fuming nitric acid to afford (XIII), its N-oxide function was reduced by treatment with phosphorus tribromide. The resultant nitro amide (XIV) was then hydrogenated to the corresponding amino amide derivative (XV), which was finally cyclized in hot ethyleneglycol to the target imidazopyranopyridine

3-Nitro-7,8-dihydro-5H-pyrano[4,3-b]pyridine (III) was prepared by heating tetrahydropyranone (I) with dinitropyridone (II) in methanolic ammonia following a reported procedure. Hydrogenation of the nitro derivative (III) and protection of the resulting amine (IV) with trichloroacetyl chloride afforded the trichloroacetamide (V). Oxidation of the pyridine ring of (V) with 3-chloroperoxybenzoic acid gave the N-oxide (VI). Nitration of the pyridine ring of (VI) with fuming nitric acid, followed by amide hydrolysis with ammonium hydroxide provided the 3-amino-4-nitropyridine N-oxide (VII). Reduction of the N-oxide and 4-nitro groups of (VII) was accomplished in a single step by hydrogenation in the presence of Raney-nickel to furnish the bicyclic diaminopyridine (VIII). Subsequent monoacylation of (VIII) with isoxazole-3-carbonyl chloride (IX) followed by thermal cyclization provided the desired imidazopyranopyridine compound (1,2), which was finally isolated as the title phosphate salt

In a different synthetic strategy, dienamine (XVIII) was obtained by heating the tetrahydropyranone enamine (XVI) with the (aminomethylene)oxazolone (XVII) in the presence of Ac2O in toluene. Thermal cyclization of (XVIII) in hot N-methylpyrrolidinone gave rise to the pyridopyranone (XIX). Upon chlorination of pyridone (XIX) with POCl3 in the presence of DMF, a simultaneous displacement of the benzoyl group occurred, leading to the formamidino derivative (XX), which was further hydrolyzed to the 3-amino-4-chloropyridine (XXI) under acidic conditions. Acylation of amine (XXI) with acid chloride (IX) afforded the corresponding amide (XXII). This was converted to the required amidine (XXIII) by chlorination with PCl5, followed by treatment with isopropanolic ammonia. Finally, the tricyclic imidazo-fused compound was obtained by thermal cyclization of the chloro amidine (XXIII) in NMP at 215 C