GENERAL STEPS: To a stirred suspension of 4-(4-phenylquinazolin-2-ylamino)benzoic acid (1.19 g, 3.49 mmol) prepared as described in Example 10 in dichloromethane (50 mL) was added catalytic amounts of dimethylformamide (100 μL) and thionyl chloride (1.50 mL, 20.6 mmol), and the resulting mixture was stirred at room temperature overnight. The solid was filtered, washed with hexane and dried under reduced pressure (high vacuum) to afford 4-(4-phenylquinazolin-2-ylamino)benzoyl chloride as a yellow solid (1.21 g, 97%). This was then added batchwise to a solution of commercially available 3-amino-4-methylbenzenemethanol (600 mg, 4.37 mmol) and triethylamine (1.0 mL, 7.2 mmol) in dichloromethane (50 mL), which had been cooled to 0 °C. The mixture was then cooled to 0 °C and the solution was mixed to a temperature of 0 °C. The mixture was warmed to room temperature overnight, then the solid was collected by filtration, washed with saturated sodium bicarbonate and water and dried under reduced pressure to afford N-(5-hydroxymethyl-2-methylphenyl)-4-(4-phenylquinazolin-2-ylamino)benzamide as a pure yellow solid (1.33 g, 86%). To a dichloromethane (50 mL) suspension of N-(5-hydroxymethyl-2-methylphenyl)-4-(4-phenylquinazolin-2-ylamino)benzamide (1.88 g, 4.08 mmol) which was cooled to 0 °C was slowly added thionyl chloride (475 μL, 6.54 mmol) and the mixture was stirred at 0 °C for 2 hours. Excess thionyl chloride and dichloromethane were removed on a rotary evaporator. The residue was stirred with ether, filtered, washed with ether and dried to give N-(5-chloromethyl-2-methylphenyl)-4-(4-phenylquinazolin-2-ylamino)benzamide as a yellow solid (2.15 g, 100%). This was then added to a tetrahydrofuran solution (20 mL, 32 mmol) of 1.6 M methylamine which was cooled to 0 °C in an ice bath. The stirred mixture was warmed to room temperature overnight and then concentrated on a rotary evaporator. The residue was redissolved in dichloromethane, washed with saturated sodium bicarbonate and dried over sodium sulfate. The solvent was then removed on a rotary evaporator and the residue was purified by fast column chromatography to afford N-(2-methyl-5-((methylamino)methyl)phenyl)-4-((4-phenylquinazolin-2- yl)amino)benzamide (1.12 g, 57%) as a yellow solid.1H NMR (400 MHz, DMSO-d6): δ 10.33 (s, 1H) 9.71 (s, 1H), 8.17 (d, 2H), 8.00 (d, 2H), 7.89-7.79 (m, 5H), 7.65 (m, 3H), 7.42 (m, 1H), 7.34 (s, 1H), 7.21 (d, 1H), 7.12 (d, 1H), 3.65 (s, 2H), 2.28 (s, 3H), 2.23 (s, 3H).MS (EI) for C30H27N5O: 474.2 (MH+).
