Boronic Acid → 2-Fluoro-5-(8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-yl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a vial was added 6-chloro-N-(4-methoxybenzyl)-N-phenyl imidazo[1,2-b]pyridazin-8-amine (150 mg, 0.411 mmol) from (1a), 3-cyano-4-fluorophenylboronic acid (74.6 mg, 0.452 mmol), potassium phosphate (174 mg, 0.822 mmol), tris(dibenzylideneacetone)dipalladium (2.0 mg, 0.002 mmol) and 1,2,3,4,5-pentaphenyl-1′-(di-t-butylphosphino)ferrocene (CTC-Q-Phos) (5.8 mg, 0.008 mmol) in toluene (2 mL) under nitrogen. The solution was heated to 100° C. for 10 hours. After checking the reaction solution which showed no reaction, more palladium reagent (2.0 mg), ligand (5.8 mg) and boronic acid (74.6 mg) were added. After heating at 100° C. for another 24 hours, the reaction went to completion with no SM left. The crude product mixture was filtered through celite, concentrated in vacuo to provide 2-fluoro-5-(8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-yl)benzonitrile which was used as is in the next reaction. LC/MS, m/e 450 (M+1). HPLC Rt, 3.60 min. Waters Sunfire C18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

Provenance & Evidence