To a stirred mixture of 3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)benzenamine (Example 1-B; 26 mg, 0.10 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (22 mg, 0.11 mmol; prepared from malonic acid and 4-fluoroaniline according to the methods described in WO 2005/030140 and by Shih and Rankin, Synth. Comm. 1996, 26(4), 833-836), and CH2Cl2 (1 mL) was added EDCI (38 mg, 0.20 mmol). The reaction was stirred at room temperature for 2 days. The mixture was diluted with EtOAc (10 mL) and washed with water (3×5 mL), brine (5 mL), dried (Na2SO4), filtered, and concentrated. The crude was purified on a pre-packed Isoelute silica gel column (10 g silica), eluting with a gradient of 20% EtOAc/hexanes, 1:1 EtOAc/hexanes, 2:1 EtOAc/hexanes, and then neat EtOAc. The product was obtained as a waxy solid (5 mg, 11%). 1H NMR (400 MHz, CDCl3) δ 9.57 (s, 1H), 9.10 (s, 1H), 8.52 (m, 1H), 7.80 (m, 2H), 7.57 (m, 3H), 7.27 (m, 2H), 7.04 (m, 2H), 6.53 (d, J=4 Hz, 1H), 3.52 (s, 2H). LRMS (ESI pos) m/e 440 (M+1). HPLC: 97% purity (220 nm).
