p-Toluenesulfonic acid → 5-(4-(4-Methoxybenzylamino)-5-nitropyridin-2-ylamino)pyrazine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of palladium (II) acetate (38 mg, 0.17 mmol) and (±)-2,2″-bis(diphenylphosphino)-1,1″-binaphthalene (318 mg, 0.51 mmol) a mixture of toluene and DMF (1:1, 10 mL) was degassed under a stream of nitrogen gas with stirring for 30 minutes. After addition of 2-amino-5-cyanopyrazine (245 mg, 2.04 mmol), sodium tert-butoxide (196 mg, 2.04 mmol) and N-(4-methoxybenzyl)-2-bromo-5-nitropyridin-4-amine (575 mg, 1.70 mmol), the mixture was degassed for a further 5 minutes and then heated at 140° C. for 30 minutes in a microwave reactor. Upon cooling, the mixture was diluted with methanol and isolated by SPE using 3×2.5 g MP-TsOH cartridges, washing with methanol and then eluting with 2 M ammonia in methanol. The basic fractions were concentrated in vacuo to give the title compound (470 mg, 1.25 mmol, 73%) which was used without further purification. LCMS (2) Rt=2.18 min; m/z (ESI−) 376 (M−H); (ESI+) 378 (MH+).

Provenance & Evidence