合成路线1

Cyclization of 4-bromoaniline (Ia) with methyl vinyl ketone (II) by means of H2SO4 in refluxing dioxane affords 6-bromo-4-methylquinoline (IIIa) (1). Similarly, cyclization of 4-aminobenzonitrile (Ib) with methyl vinyl ketone (II) by means of HCl and chloranil in EtOH gives 4-methyl-6-quinolinecarbonitrile (IIIb) (2). Condensation of 4-methylquinolines (IIIa) or (IIIb) with methyl 6-methylpyridine-2-carboxylate (IV) by means of KHMDS in THF at –70 °C or t-BuONa in THF (2) produces the 2-(4-quinolinyl)-1-(pyridyl)ethanone derivatives (Va) (1) or (Vb) (2), respectively. Subsequent condensation of ketone (Va) with 1-amino-2-pyrrolidinone hydrochloride (VIa) in pyridine yields acyl hydrazone (VIIa), which is cyclized by means of Cs2CO3 in DMF at 100 °C, leading to the pyrrolopyrazole derivative (IXa) (1). Alternatively, condensation of ketone (Vb) with 1-amino-2-pyrrolidinone p-toluenesulfonate (VIb) [prepared by the hydrolysis of hydrazone (VIII) with p-TsOH·H2O in toluene] in the presence of 2,6-lutidine in refluxing DMF/toluene provides the acyl hydrazone (VIIb), which cyclizes to the pyrrolopyrazole derivative (IXb) by treatment with K2CO3 (2). Finally, methoxycarbonylation of bromoquinoline (IXa) under CO atmosphere in the presence of Pd(dppf)2Cl2 and NaOAc in MeOH at 80 °C gives the methyl ester (X), which is submitted to ammonolysis with NH3 in MeOH at 90 °C. Alternatively, nitrile (IXb) is hydrolyzed by means of H2O2 and K2CO3 in DMSO/H2O .