合成路线1

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).