Dichloromethane → 6-(2-Fluoropyridin-3-yl)-2-methylpyrimidin-4-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-2-methyl-4-pyrimidinamine (SynChem, Inc., Des Plaines, Ill.) (0.500 g, 3.48 mmol), 2-fluoropyridin-3-ylboronic acid (0.589 g, 4.18 mmol), PdCl2(dppf) complex with dichloromethane (0.199 g, 0.244 mmol) and 2 M Na2CO3 (aq., 5.22 mL, 10.45 mmol) in dioxane (17 mL) was stirred at 110° C. overnight. After cooling to RT, water was added and the mixture was filtered through Celite® (diatomaceous earth). The mixture was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column (40 g), eluting with a gradient of 0% to 5% MeOH in CH2Cl2, to provide 6-(2-fluoro-3-pyridinyl)-2-methyl-4-pyrimidinamine (0.173 g, 0.85 mmol, 24% yield) as an off-white solid. m/z (ESI, +ve) 205.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 8.52-8.62 (m, 1H); 8.27-8.34 (m, 1H); 7.44-7.61 (m, 2H); 7.00 (br. s., 1H); 6.75-6.83 (m, 1H); 2.39 (s, 3H).

Provenance & Evidence