Bromide ion → [5-(5-Chloro-2-methoxypyridin-3-yl)-2-(methylthio)pyrimidin-4-yl]methanol

Participants

Reaction Conditions

Reaction Steps

[5-Bromo-2-(methylthio)pyrimidin-4-yl]methanol (INTERMEDIATE 1, 1.9 g, 8.08 mmol), 5-chloro-2-methoxypyridin-3-ylboronic acid (1.51 g, 8.08 mmol) and K2CO3 (3.35 g, 24.24 mmol) were added to a round bottom flask, which was then evacuated and charged with nitrogen 3 times. THF (30 mL) and water (6 mL) were then added. After evacuating and charging again with nitrogen, 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.527 g, 0.808 mmol) was added and the reaction heated for 30 minutes at 50° C. LCMS showed 80% conversion to product plus 20% unreacted bromide. The reaction was diluted with 15 mL acetonitrile and filtered through a 4 g C18 cartridge, eluting with 50 mL acetonitrile until the filtrate was colorless. The filtrate was then concentrated. Silica gel chromatography using a 0-50% isopropyl acetate/hexanes linear gradient followed by an isocratic hold of 50% isopropyl acetate/hexanes gave an 80/20 inseparable mixture of title compound and recovered starting material, which was more thoroughly purified later in the synthetic route. LCMS (M+H)+: 298.3 Title compound. LCMS (M+H)+: 237.1 Starting material (INTERMEDIATE 1).

Provenance & Evidence