Potassium Phosphate, Tribasic → HCID 69708574, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-7-dimethoxymethylimidazo[1,2-α]pyrimidine (1.36 g, 5 mmol), potassium phosphate (2.12 g, 10 mmol), 2′-fluoro-5′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile (2.42 g, 7.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (230 mg, 0.2 mmol) in N,N-dimethylformamide (15 ml) was heated at 80° C. for 14 h. The reaction was cooled and partitioned between ethyl acetate and water. The organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness to afford crude 5′-(7-dimethoxymethylimidazo[1,2-α]pyrimidin-3-yl)-2′-fluorobiphenyl-2-carbonitrile. The residue was suspended in 1,4-dioxane (30 ml) then treated with 3N hydrochloric acid (30 ml) and this mixture was heated at 60° C. for 14 h. The reaction was cooled and partitioned between dichloromethane and water. The organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica gel eluting with dichloromethane (+1% triethylamine) on a gradient of methanol (1-4%) gave a solid. Trituration with ether afforded 2′-fluoro-5′-(7-formylimidazo[1,2-α]pyrimidin-3-yl)biphenyl-2-carbonitrile as a yellow powder (1.2 g, 70% over 2 steps): δH (400 MHz, DMSO) 7.48 (1H, d, J 7), 7.65-7.72 (2H, m), 7.75-7.80 (1H, m), 7.87 (1H, ddd, J 8, 8 and 1), 7.95-7.99 (2H, m), 8.02-8.05 (1H, m), 8.40 (1H, s), 9.27 (1H, dd, J 7 and 1), 9.96 (1H, s); m/z (ES+) 343 (M++H).

Provenance & Evidence