Propionitrile → (E)-tert-Butyl 3-(3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylate

Participants

Reaction Steps

tert-Butyl acrylate (2.74 mL, 18.6 mmol), diisopropylethylamine (1.6 mL, 9.8 mmol) and P(o-tolyl)3 (272 mg, 0.89 mmol) were successively added to a suspension of 6-bromo-1H-imidazo[4,5-b]pyridin-2(3H)-one (1.0 g, 4.67 mmol) in propionitrile (27 mL) and dimethylformamide (7 mL) at room temperature. The resulting mixture was purged with argon prior to the addition of palladium acetate (100 mg, 0.44 mmol). The mixture was then purged with argon a second time and refluxed overnight. The reaction mixture was filtered on Celite® and the filtrate was concentrated to dryness. The residue was partitioned between ethyl acetate (20 mL) and water (30 mL). The organic phase was washed with a saturated solution of sodium chloride (2×30 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was triturated in diethyl ether to give the title product as a brown solid (667 mg, 56%).

Provenance & Evidence