Reaction Steps
4-Chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.4126 g, 3.6704 mmol), 2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-ylboronic acid (1.2342 g, 4.2390 mmol), Am-Phos (140.4 mg, 0.1983 mmol), and potassium acetate (1.531 g, 15.60 mmol) were suspended in 1,4-dioxane (20 mL) and water (4 mL), and nitrogen was bubbled through the suspension for 15 s. Then, the flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.), and stirred under nitrogen overnight. Then, the reaction was cooled to room temperature, diluted with water (40 mL), and extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered through a Celite® (diatomaceous earth) pad, concentrated, and purified on a silica gel filter (600 mL fritted filter with about 3 inches of silica gel; DCM to 100:1 DCM/MeOH to 75:1 DCM/MeOH). The fractions with product were collected, concentrated, and dried under high vacuum, first at room temperature, and then in a water bath (about 50° C.) to give 4-(2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.797 g). 1H NMR (CDCl3, 400 MHz) δ 8.34 (dd, J=8.90 Hz, 2.45 Hz, 1H), 8.15 (d, J=1.96 Hz, 1H), 7.24-7.17 (m, 6H), 7.16-7.11 (m, 2H), 6.86 (dd, J=10.17 Hz, 8.61 Hz, 4H), 4.82 (s, 2H), 4.78 (s, 2H), 4.20 (q, J=7.30 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 2.53 (s, 3H), 2.45 (s, 3H), 1.67 (d, J=7.24 Hz, 3H). m/z (ESI, pos. ion) 596 (M+H)+.
