The acetylation of 2-methyl-3-aminobenzonitrile (I) with acetic anhydride in refluxing acetic acid gives 2-methyl-3-acetylaminobenzonitrile (II), which is reduced with Raney-Ni in refluxing 50% formic acid yielding 2-methyl-3-acetylaminobenzaldehyde (III). The condensation of (III) with malonic acid (IV) by means of piperidine in pyridine affords 2-methyl-3-acetylaminocinn acid (V), which is converted to the corresponding azide (VI) by reaction with ethyl chloroformate and sodium azide by means of triethylamine in acetone. The cyclization of (VI) by heating at 240 C in diphenyl ether gives 1-hydroxy-5-methyl-6-acetylaminoisoquinoline (VII), which is hydrolyzed with HCl in refluxing ethanol to 1-hydroxy-5-methyl-6-aminoisoquinoline (VIII). The condensation of (VIII) with 4-chloro-3-nitropyridine (IX) in DMF affords 1-hydroxy-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (X).

Compound (X) is reduced with H2 over Pd/C in acetic acid to 1-hydroxy-5-methyl-6-[(3-amino-4-pyridyl)amino]isoquinolin (Xl). The treatment of (XI) with NaNO2 in acetic acid yields 1-(1-hydroxy-5-methyl-6-isoquinolyl)triazolo[4,5-c]pyridine (XII), which is converted into 1-hydroxy-5-methyldipyrido[4,3-b][3,4-f]indole (XIII). The reaction of (XIII) with PCl5 in refluxing POCl3 gives 1-chloro-5-methyldipyrido[4,3-b][3,4-f]indole (XIV), which is finally condensed with 3-(diethylamino)propylamine (XV) by heating at 150 C.

Reaction of 2-chloronicotinonitrile (I) with 1-methyl-3-phenylpiperazine (II) gives 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarbonitrile (III), which is hydrolyzed to the carboxylic acid, which is reducted to the hydroxymethyl derivative (IV). Cyclization of (IV) in concentrated sulfuric acid at 20-35 C gives the title compound after 2 h and treatment with ammonia.

The acetylation of 2-methyl-3-aminobenzonitrile (I) with acetic anhydride in refluxing acetic acid gives 2-methyl-3-acetylaminobenzonitrile (II), which is reduced with Raney-Ni in refluxing 50% formic acid yielding 2-methyl-3-acetylaminobenzaldehyde (III). The condensation of (III) with malonic acid (IV) by means of piperidine in pyridine affords 2-methyl-3-acetylaminocinn acid (V), which is converted to the corresponding azide (VI) by reaction with ethyl chloroformate and sodium azide by means of triethylamine in acetone. The cyclization of (VI) by heating at 240 C in diphenyl ether gives 1-hydroxy-5-methyl-6-acetylaminoisoquinoline (VII), which is hydrolyzed with HCl in refluxing ethanol to 1-hydroxy-5-methyl-6-aminoisoquinoline (VIII). The condensation of (VIII) with 4-chloro-3-nitropyridine (IX) in DMF affords 1-hydroxy-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (X).

Compound (X) is reduced with H2 over Pd/C in acetic acid to 1-hydroxy-5-methyl-6-[(3-amino-4-pyridyl)amino]isoquinolin (Xl). The treatment of (XI) with NaNO2 in acetic acid yields 1-(1-hydroxy-5-methyl-6-isoquinolyl)triazolo[4,5-c]pyridine (XII), which is converted into 1-hydroxy-5-methyldipyrido[4,3-b][3,4-f]indole (XIII). The reaction of (XIII) with PCl5 in refluxing POCl3 gives 1-chloro-5-methyldipyrido[4,3-b][3,4-f]indole (XIV), which is finally condensed with 3-(diethylamino)propylamine (XV) by heating at 150 C.

1-hydroxy-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (X) is heated with phosphorous chloride oxide to give 1-chloro-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (XVI), which is reduced with H2 over Raney-Ni giving 6-[(3-amino-4-pyridyl)amino]-1-chloro-5-methylisoquinoline (XVII). This compound is treated with sodium nitrite to give 1-(1-chloro-5-methyl-6-isoquinolyl)triazolo[4,5-c]pyridine (XVIII), which is cyclized to 1-chloro-5-methylpyrido[4,3-b][3,4-f]indole (XIV), which is finally condensed with 3-(diethylamino)propylamine (XV) by heating at 150 C.

The acetylation of 2-methyl-3-aminobenzonitrile (I) with acetic anhydride in refluxing acetic acid gives 2-methyl-3-acetylaminobenzonitrile (II), which is reduced with Raney-Ni in refluxing 50% formic acid yielding 2-methyl-3-acetylaminobenzaldehyde (III). The condensation of (III) with malonic acid (IV) by means of piperidine in pyridine affords 2-methyl-3-acetylaminocinn acid (V), which is converted to the corresponding azide (VI) by reaction with ethyl chloroformate and sodium azide by means of triethylamine in acetone. The cyclization of (VI) by heating at 240 C in diphenyl ether gives 1-hydroxy-5-methyl-6-acetylaminoisoquinoline (VII), which is hydrolyzed with HCl in refluxing ethanol to 1-hydroxy-5-methyl-6-aminoisoquinoline (VIII). The condensation of (VIII) with 4-chloro-3-nitropyridine (IX) in DMF affords 1-hydroxy-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (X).

Compound (X) is reduced with H2 over Pd/C in acetic acid to 1-hydroxy-5-methyl-6-[(3-amino-4-pyridyl)amino]isoquinolin (Xl). The treatment of (XI) with NaNO2 in acetic acid yields 1-(1-hydroxy-5-methyl-6-isoquinolyl)triazolo[4,5-c]pyridine (XII), which is converted into 1-hydroxy-5-methyldipyrido[4,3-b][3,4-f]indole (XIII). The reaction of (XIII) with PCl5 in refluxing POCl3 gives 1-chloro-5-methyldipyrido[4,3-b][3,4-f]indole (XIV), which is finally condensed with 3-(diethylamino)propylamine (XV) by heating at 150 C.

1-hydroxy-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (X) is heated with phosphorous chloride oxide to give 1-chloro-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (XVI), which is reduced with H2 over Raney-Ni giving 6-[(3-amino-4-pyridyl)amino]-1-chloro-5-methylisoquinoline (XVII). This compound is treated with sodium nitrite to give 1-(1-chloro-5-methyl-6-isoquinolyl)triazolo[4,5-c]pyridine (XVIII), which is cyclized to 1-chloro-5-methylpyrido[4,3-b][3,4-f]indole (XIV), which is finally condensed with 3-(diethylamino)propylamine (XV) by heating at 150 C.