253-72-5

504-24-5

107-21-1

253-72-5

The general procedure for the synthesis of 1,6-naphthyridine from 4-aminopyridine and ethylene glycol was as follows: first, a sulfuric acid solution was prepared by slowly adding 100 mL of concentrated sulfuric acid to 57 mL of water cooled in an ice bath. Subsequently, 33 mL of glycerol (457 mmol), 48 g of m-nitrobenzenesulfonic acid sodium salt (212 mmol), and 10 g of 4-aminopyridine (106 mmol) were sequentially added to this solution. The reaction mixture was heated to reflux at 135 °C for 4 hours. Upon completion of the reaction, the cooled reaction mixture was alkalized with 500 mL of 2.5 N sodium hydroxide solution and cooled in an ice bath. Subsequently, extraction was performed with dichloromethane (3 x 200 mL). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to give an oil. The oily substance was purified by column chromatography (5% methanol/dichloromethane as eluent) to give 5.04 g (36% yield) of dark orange oily product. For the preparation of analytical samples, the product was converted to HCl salt and recrystallized from ethyl acetate to give an orange low melting point solid. Mass spectrometry analysis showed a molecular ion peak m/z 130 (M+). Ref: Chem Pharm Bull. 1971, 19, 9, 1751-1755.