Reaction Steps
To a stirred solution of acid 225 (300 mg, 0.646 mmol) in DMF (10 mL) at 0° C. were added HOBT (198 mg, 1.292 mmol), EDC (248 mg, 1.292 mmol) and 1-methyl-4-(piperidin-4-yl)piperazine (118 mg, 0.646 mmol). The reaction mixture was stirred at room temperature overnight, diluted with NaHCO3 saturated solution, and extracted with EtOAc. The extract was dried over anhydrous Na2SO4 and concentrated in vacuum. The residue was purified three times by Biotage (MeOH/EtOAc, 0-50%, 25 g column) followed by purification on Gilson [MeOH/H2O, 50-95%, HCOOH (0.05%)] to afford the title compound 234 (50 mg, 0.079 mmol, 12.29% yield) as a mono-formate salt. NMR (400 MHz, CD3OD) δ (ppm): 8.67 (dd, J1=0.8 Hz, J2=2.1 Hz, 1H,), 8.48 (s, 1H), 8.47 (s, 1H), 8.19 (dd, J1=0.8 Hz, J2=8.3 Hz, 1H), 8.16 (s, 1H), 7.97 (dd, J1=2.2 Hz, J2=8.2 Hz, 1H), 7.65 (dd, J1=2.4 Hz, J2=13.1 Hz, 1H), 7.29 (t, 1H, J=8.8 Hz, 1H), 7.20-7.18 (m, 1H), 6.65 (dd, J1=0.8 Hz, J2=5.5 Hz, 1H), 3.83 (br. s, 1H), 3.24 (br s, 1H), 3.01 (br. s, 6H), 2.85 (br. s, 3H), 2.76-2.70 (m, 2H), 2.67 (s, 3H), 2.61-2.57 (m, 1H), 2.02 (br. s, 1H), 1.91-1.85 (br. s, 1H), 1.56-1.49 (hr. s, 2H), 0.78-0.74 (m, 2H), 0.55-0.51 (m, 2H). MS: 630.4 (MH)+
