179943-57-8

Dowtherm (50 mL) was added to a 100 mL two-necked round-bottomed flask and heated to 250 °C in a sand bath. Maintaining this temperature, diethyl {[(3-bromophenyl)amino]methylene}malonate (Intermediate 32, 10.0 g, 29.2 mmol) was added to the reaction system and the reaction was continued at 250 °C for 1 hour. After completion of the reaction, the reaction mixture was cooled to room temperature and a white solid was collected by filtration and dried to give ethyl 7-bromo-4-oxo-1,4-dihydroquinoline-3-carboxylate 6.0 g in 69.3% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 1.07 (t, 3H), 1.22 (s, 12H), 3.16 (q, 2H), 7.29 (m, 1H), 7.31 (d, 2H), 7.61 (s, 1H), 7.88 (s, 1H), 8.31 (s, 1H), 8.65 (s, 1H), and 9.44 (s, 1H).

[1] Journal of Medicinal Chemistry, 2015, vol. 58, # 14, p. 5522 - 5537
[2] Patent: WO2009/147433, 2009, A1. Location in patent: Page/Page column 279
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 15, p. 4790 - 4800
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 4, p. 1010 - 1013
[5] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 15, p. 5055 - 5058