16675-62-0

67-56-1

99-05-8

56-81-5

16675-62-0

Synthesis of methyl quinoline-5-carboxylate (Intermediate-97): To a 500 mL round-bottom flask equipped with a magnetic stirrer was added 90 mL of concentrated sulfuric acid solution of m-aminobenzoic acid (60 g, 435 mmol), glycerol (168 g, 1824 mmol) and 3-nitrobenzoic acid (30 g, 179 mmol). The reaction mixture was heated and stirred at 150°C for 7 hours. Upon completion of the reaction, the mixture was cooled to room temperature, methanol (600 mL) was added and refluxed for 12 hours. Subsequently, the mixture was cooled to 0°C, the reaction was quenched with ice water and concentrated under reduced pressure. The crude product was alkalized with aqueous sodium bicarbonate, extracted with dichloromethane and concentrated by combining the organic phases. The crude product was purified by silica gel column chromatography with the eluent being a solvent mixture of petroleum ether (60-80°C fraction), ethyl acetate and 0.5% triethylamine. Methyl quinoline-5-carboxylate (Intermediate-97) was finally obtained as a brown liquid (21 g).