Example 4: (5-Chloro-2-((E)-3-(3-(4-fluorophenyl)-3,8-diazanaphthalen-1-yl)-3-oxopropenyl)-4-methylphenyl)urea; a) Synthesis of 2-bromo-5-chloro-4-methylaniline; 3-chloro-4-methylaniline (20.0 g, 0.141 mol) was dissolved in dichloromethane (200 mL) and a 5 minute A solution of N-bromosuccinimide (NBS, 25.1 g, 0.141 mol) in dichloromethane (800 mL) was added slowly over 5 min. The reaction mixture was stirred at room temperature for 5 minutes. Subsequently, the reaction solution was concentrated to about 200 mL and diluted with hexane (1000 mL). The precipitate was collected by filtration, and the filtrate was concentrated and dried and purified by silica gel column chromatography (eluent: hexane/tert-butyl methyl ether, 10:1) to afford the title compound as yellow crystals (12.3 g, 40% yield). A second title compound (7.5 g, 24% yield) was obtained by re-chromatographing the mixed grades.1H-NMR (400 MHz, DMSO-d6) δ (ppm): 2.13 (s, 3H); 5.32 (s, 2H, NH2); 6.81 (s, 1H); 7.31 (s, 1H). Mass spectra (m/z) ES+: 221 (100, [M]+); 219 (80); 184 (35); 140 (100); 104 (50); 77 (65); 52 (58); 51 (60).
