[Synthesis]
General procedure for the synthesis of 2-((2-((2-methoxy-4-morpholinophenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide from 2-methoxy-4-morpholinophenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide: In a microwave tube, 2-{[2-chloro-5- (trifluoromethyl)-4-pyridinyl]amino}-N-methylbenzamide (Intermediate 1, 50 mg, 0.152 mmol) was mixed with 2-methoxy-4-morpholinoaniline (148 mg, 0.607 mmol), 1M hydrochloric acid (0.303 mL, 0.303 mmol), 1,4-dioxane (0.2 mL) and water (2.5 mL). The mixture was placed in a microwave reactor and irradiated at 170°C for 25 minutes. After completion of the reaction, the crude product was collected by filtration and the filtrate was purified by reversed-phase high performance liquid chromatography (HPLC) to afford the target compound 2-((2-((2-methoxy-4-morpholinophenyl)amino)-5-(trifluoromethyl)pyridin-4-yl)amino)-N-methylbenzamide (35.5 mg, 0.071 mmol, 46.7% yield). Mass spectrum (MS): molecular weight of molecular formula C25H26F3N5O3 (M) = 471.48, (M+H)+ =472; 1H NMR (400 MHz, methanol-d4) δppm 2.88 (s, 3H), 3.05-3.14 (m, 4H), 3.78-3.91 (m, 7H), 6.45 (s, 1H), 6.52 ( dd, J=8.59,2.53Hz, 1H), 6.64 (d, J=2.53Hz, 1H), 7.03-7.13 (m, 1H), 7.30 (d, J=8.59Hz, 1H), 7.40-7.50 (m, 2H), 7.61 (dd, J=7.83,1.26Hz, 1H), 8.10 (s, 1H). |