2‐Fluoro‐6‐(pyrimidin‐5‐yl)aniline 1

Abstract

[1697040-97-3] C10H8FN3 (MW 189.19) InChI = 1S/C10H8FN3/c11-9-3-1-2-8(10(9)12)7-4-13-6-14-5-7/h1-6H,12H2 InChIKey = RLVGAYVNMWBWFQ-UHFFFAOYSA-N (meta-selective transient directing group) Physical Appearance: white solid. Melting Point: 164–166 °C. Solubility: soluble in most organic solvents such as hexafluoroisopropanol (HFIP), dichloromethane, chloroform, ethyl acetate, and acetonitrile. Analytical Data: 1H NMR (400 MHz, CDCl3) δ (ppm) 9.17 (s, 1H), 8.85 (s, 2H), 7.06 (ddd, J = 10.7, 8.1, 1.4 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.79 (td, J = 7.9, 5.1 Hz, 1H), 3.86 (s, 2H). 13C NMR (101 MHz, CDCl3) δ (ppm) 157.70, 156.79, 150.65 (s), 132.81 (d, J = 13.4 Hz), 132.39 (d, J = 3.2 Hz), 125.63 (d, J = 3.2 Hz), 121.89 (d, J = 3.5 Hz), 118.54 (d, J = 7.8 Hz), 115.74 (d, J = 19.2 Hz). 19F NMR (471 MHz, CDCl3) δ (ppm) −133.51. IR (thin film, cm−1): 1062, 1182, 1215, 1246, 1277, 1299, 1344, 1412, 1488, 1555, 1580, 1652, 2855, 2925, 3219, 3339, 3433. Preparative Method: To a solution of 2-fluoro-6-(pyrimidin-5-yl)aniline (1.0 equiv) in dioxane (10 mL) were added Et3N (4.0 equiv), PdCl2(dppf) (5 mol %), and pinacolborane (3.0 equiv) dropwise. The mixture was stirred at 100 °C for 6 h, then cooled to room temperature, and water (1.0 mL), Ba(OH)2·8H2O (3.0 equiv), and 5-bromopyrimidine (0.92 equiv) were successively added. The mixture was stirred at 100 °C for 12 h before addition of water (25 mL) at room temperature. The mixture was filtered through Celite. The eluent was extracted with ethyl acetate, and the organic layer was purified by column chromatography using silica gel deactivated with 10 mol % Et3N in hexane. 2-Fluoro-6-(pyrimidin-5-yl)aniline was isolated as white solid.1 Handling, Storage, and Precautions: The compound is stable under atmospheric conditions and does not undergo decomposition over a period of time when stored in a sealed container. It is safe to handle, without any risk of burns or inflammation.