Synthesis
4,7-Dichloroquinoline (2.00 g, 10.1 mmol), piperazine (4.35 g, 50.5 mmol, 5.0 eq.) and triethylamine (2.81 mL, 20.2 mmol, 2.0 eq.) were added to the reaction vial. The reaction vial was sealed under nitrogen protection and heated to 130 °C. Gradual dissolution of the solid was observed to form a clarified orange-yellow solution. A yellow precipitate appeared during the reaction. The progress of the reaction was monitored by thin layer chromatography (TLC) (unfolding agent: 5% v/v dichloromethane solution of methanol) and the reaction was completed after about 4 hours. The reaction mixture was cooled to room temperature and diluted with dichloromethane (25 mL) and water (25 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (3 x 25 mL). The organic phases were combined, washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a yellow solid crude product (2.60 g). The crude product was purified by silica gel column chromatography (eluent: dichloromethane/methanol, 100/0 to 98/2) to afford 7-chloro-4-(1-piperazinyl)quinoline (2.44 g, 9.85 mmol, 98% yield) as a yellow solid. The 1H NMR and 13C NMR data of the product were in agreement with literature reports.1H NMR (300 MHz, CDCl3): δ 8.71 (d, J = 4.9 Hz, 1H), 8.03 (d, J = 2.0 Hz, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.41 (dd, J = 2.0, 9.0 Hz, 1H), 6.82 (d, J = 2.0, 9.0 Hz, 1H), 7.41 (dd, J = 2.0, 9.0 Hz, 1H). 6.82 (d, J = 5.0 Hz, 1H), 3.17 (br s, 4H), 3.16 (br s, 4H); 13C NMR (75 MHz, CDCl3): δ 157.3, 151.9, 150.1, 134.7, 128.8, 126.0, 125.2, 121.9, 108.9, 53.5, 46.0; ESI-MS: m/z 248.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5502 - 5505
[2] Indian Journal of Heterocyclic Chemistry, 2010, vol. 19, # 3, p. 215 - 220
[3] Journal of Medicinal Chemistry, 1998, vol. 41, # 22, p. 4360 - 4364
[4] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 10, p. 2882 - 2886
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 17, p. 4733 - 4736
