合成路线1

N-Protection of 2-amino-5-nitrophenol (XVII) with Ac2O in the presence of AcOH gives N-(2-hydroxy-4-nitrophenyl)acetamide (XXI), which upon O-alkylation with ethyl bromide (XX) in the presence of K2CO3 in DMF at 60 °C affords N-(2-ethoxy-4-nitrophenyl) acetamide (XXII). Reduction of the nitro derivative (XXII) with H2 over Pd/C in THF furnishes the corresponding aniline (XXIII), which by condensation with ethyl 2-cyano-3-ethoxy-2-propenoate (XXIV) at reflux produces enamine (XXV). Thermal cyclization of enamino ester (XXV) in Dowtherm at 250 °C then yields 4-hydroxyquinoline derivative (XXVI) , which upon chlorination with POCl3 in 1,2-diethoxyethane at 80-85 °C affords N-(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide (VII) . Alternatively, condensation of ethyl cyanoacetate (II) with morpholine (XXVII) at 100-110 °C gives 4-(cyanoacetyl)morpholine (XXVIII), which after coupling with 4-acetamido-3-ethoxyaniline (XXIII) in the presence of triethyl orthoformate in i-PrOH at 50-60 °C produces the arylamino propenamide (XXIX). Finally, cyclization of (XXIX) in the presence of POCl3 in acetonitrile at 60-65 °C then leads to the target intermediate (VII) .