4-Fluoroaniline → N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Participants

Reaction Steps

To a stirred mixture of 1-((4-fluorophenyl)carbamoyl)-cyclopropanecarboxylic acid (867 mg, 3.88 mmol; prepared from cyclopropane-1,1-dicarboxylic acid and 4-fluoroaniline using the methods described in WO 2005/030140 and by Shih and Rankin, Synth. Comm. 1996, 26(4), 833-836) and a catalytic amount of DMF (10 μL) in THF (10 mL) was added oxalyl dichloride (0.33 mL, 3.9 mmol) dropwise. After stirring at room temperature for 30 minutes, a solution of 3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)benzenamine (Example 6, Step A; 600 mg, 1.55 mmol) in THF (2 mL) was added. After stirring for 1 hour at room temperature, the reaction was diluted into aqueous saturated NaHCO3 (50 mL) and water (50 mL). The product was extracted with EtOAc, washed with brine, dried (Na2SO4), filtered and concentrated. The product was purified by Biotage 40S silica gel column eluting with 2:1 EtOAc/hexanes. The product was obtained as a fluff-y white solid (745 mg, 67%). 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 8.41 (d, J=6 Hz, 1H), 8.34 (s, 1H), 7.74 (m, 2H), 7.44 (m, 2H), 7.22 (m, 2H), 7.06 (m, 2H), 6.46 (d, J=6 Hz, 1H), 1.79 (m, 2H), 1.61 (m, 2H). LRMS (ESI pos) m/e 592 (M+1).

Provenance & Evidence