5-Aminopyrazine-2-carbonitrile → Tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate

Participants

Reaction Steps

Palladium (II) acetate (14.7 mg, 0.07 mmol) was added to (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (123 mg, 0.2 mmol) in DMF-toluene (1:1, 5 mL) and the mixture was degassed for 10 minutes under a stream of nitrogen gas. 2-Amino-5-cyanopyrazine (95 mg, 0.79 mmol), sodium-t-butoxide (76 mg, 0.79 mmol) and tert-butyl 4-((2-bromo-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate (273 mg, 0.67 mmol) were added and the mixture was degassed for a further 5 minutes before stirring at room temperature for 2 hours. The mixture was partitioned between ethyl acetate and water and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with water and brine, then dried (Na2SO4) and concentrated to give crude tert-butyl 4-((2-(5-cyanopyrazin-2-ylamino)-5-nitropyridin-4-yloxy)methyl)piperidine-1-carboxylate (379 mg) which was used without further purification.

Provenance & Evidence