4-Fluoroaniline → HCID 67349569, compound

Participants

Reaction Steps

A 100 mL, single-neck, round-bottomed flask was charged with 1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxylic acid (0.2773 g, 1.243 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 THF (10 mL). Catalytic DMF (10 microliters) was added to the reaction mixture. While stirring oxalyl dichloride (0.1067 mL, 1.243 mmol) was added dropwise, and the reaction mixture was stirred for 30 minutes. 4-(2-Iodothieno[3,2-b]pyridin-7-yloxy)benzenamine (example 72, Step A 0.500 g, 0.8284 mmol) in THF (2 mL) was added, and the reaction mixture was stirred for 1 hour, water (50 mL) and saturated NaHCO3 (50 mL) were added. The reaction mixture was extracted with EtOAc, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified on a Biotage 40S column (2:1 EtOAc/Hexane). The product was a beige solid (155 mg, 29%). 1H NMR (CDCl3, 400 MHz) δ 9.37 (s, 1H), 8.59 (s, 1H), 8.41 (d, J=6 Hz, 1H), 7.76 (s, 1H), 7.62 (d, J=9 Hz, 2H), 7.46 (m, 2H), 7.15 (d, J=9 Hz, 2H), 7.06 (t, J=9 Hz, 2H), 6.51 (d, J=6 Hz, 1H), 1.71 (m, 4H). LRMS (ESI pos) m/e 574 (M+1).

Provenance & Evidence