Dichloromethane → 1-(2-{5-Chloro-4-[7-(5-chloro-2-fluoropyridin-4-yl)-benzo[b]thiophen-2-yl]pyrimidin-2-ylamino}ethyl)imidazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, combine 1-{2-[4-(7-bromo-benzo[b]thiophen-2-yl)-5-chloro-pyrimidin-2-ylamino]-ethyl}-imidazolidin-2-one (500 mg, 1.1 mmol), 5-chloro-2-fluoropyridine-4-boronic acid (578 mg, 3.3 mmol), [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (90 mg, 0.11 mmol), 2-(di-tert-butylphosphino)biphenyl (20 mg, 0.066 mmol) and sodium carbonate (350 mg, 3.3 mmol) in THF (3 mL) and water (1.5 mL). Bubble nitrogen through the mixture for 5 min. Heat the mixture to 100° C. for 10 min. Concentrate the organic layer to dryness in vacuo. Slurry the resulting solid into dichloromethane/methanol and purify by column chromatography (1% 2 N ammonia/methanol solution in dichloromethane to 10% 2 N ammonia/methanol solution in dichloromethane) to afford the title compound. For further purification, dissolve the product in DMSO and purify by reverse phase column chromatography (50% acetonitrile in water (with 0.03% HCl) to 95% acetonitrile in water (with 0.03% HCl) to afford the title compound (146 mg, 26%). MS (ES) m/z 503 [M+1]+.

Provenance & Evidence