[Synthesis]
Step 2. Synthesis of N-(3-fluoro-4-((2-(5-(((2-methoxyethyl)amino)methyl)pyridin-2-yl)thieno[3,2-b]pyridin-7- yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1 -dicarboxamide (147): Compound 146 (0.59 g, 0.81 mmol) was dissolved in dichloromethane (50 mL) in dichloromethane (50 mL) and trifluoroacetic acid (TFA, 3 mL) was added. The reaction mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the solution was concentrated to remove the solvent. The residue was partitioned between dichloromethane and 1 M sodium hydroxide solution and filtered to remove insoluble impurities. The organic phase was separated, washed sequentially with 1 M sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated to afford the target compound 147 (0.35 g, 69% yield).1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.40 (s, 1H), 10.01 (s, 1H), 8.55 (d, J = 1.6 Hz 1H), 8.51 (d, J = 5.3 Hz, 1H), 8.31 (s, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.92-7.87 (m, 2H), 7.65-7.61 (m, 2H), 7.52-7.43 (m, 2H), 7.17-7.12 (m, 2H), 6.64 (d, J = 5.5 Hz, 1H), 3.77 (s, 2H), 3.40 (t, J = 5.7 Hz, 2H), 3.23 (s, 3H), 2.64 (t, J = 5.7 Hz, 2H), 1.46 (br s, 4H). Mass spectrum (m/z): 630.1 (M + H). |