6-Bromo-2-methoxy-3-(4-methyl-1H-imidazol-1-yl)pyridine

1123194-97-7

1123194-98-8

Ammonium acetate (43 g, 553 mmol) was dissolved in acetic acid (208 mL) under argon protection and stirred for 30 minutes at room temperature. Subsequently, N-(6-bromo-2-methoxypyridin-3-yl)-N-(2-oxopropyl)formamide (32 g, 111 mmol) was added to the mixture and kept at room temperature. The reaction system was warmed up to 130 °C with continuous stirring for 4 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming complete consumption of the raw materials, the reaction mixture was diluted with ice water (200 mL) and the pH was adjusted to 7 with 50% sodium hydroxide solution (200 mL), at which point a solid precipitated. The solid was collected by filtration, washed with ether (100 mL) and dried under vacuum to afford the target product 6-bromo-2-methoxy-3-(4-methyl-1H-imidazol-1-yl)pyridine (17.5 g, 60% yield) as an off-white solid. The product was characterized by 1H NMR (CDCl3, 400 MHz) and LCMS: 1H NMR δ 7.72 (s, 1H), 7.39 (d, 1H), 7.16 (d, 1H), 6.91 (s, 1H), 4.03 (s, 3H), 2.29 (s, 3H); LCMS purity 99.3%, m/z 267.9 ([M+H]+) Chromatographic conditions: Ascentis Express C-18 column (50 x 3.0 mm, 2.7 μm), retention time 1.54 min, mobile phase 0.025% TFA aqueous solution + 5% acetonitrile: acetonitrile + 5% 0.025% TFA aqueous solution, gradient elution (0.0/5, 0.5/5, 3/100, 5/100), flow rate 1.2 mL/min; TLC unfolding agent was 40% ethyl acetate/hexane (Rf 0.2).