Cesium carbonate → (+/-)-(4aR,8aR)-tert-butyl 6-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

2-chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 10) (85.0 mg, 0.248 mmol), (+/−)-(4aR,8aR)-tert-butyl 6-(3-amino-2-chloro-5-cyanophenyl)octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (97.0 mg, 0.248 mmol), DPPF (9.62 mg, 0.017 mmol), Cs2CO3 (137 mg, 0.422 mmol), Xantphos (14.35 mg, 0.025 mmol), Palladium(II)Acetate (16.7 mg, 0.074 mmol) and 1,4-dioxane (2 ml) were combined in a microwave vial. The vial was evacuated and backfilled with Nitrogen (3×). The reaction stirred at 100° C. for 3 hr. The reaction mixture cooled to 25° C., diluted with EtOAc, washed with brine and dried (Na2SO4). The solvents were removed and the material purified on silica gel 25% EtOAc in DCM to afford (+/−)-(4aR,8aR)-tert-butyl 6-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrido[3,4-b][1,4]oxazine-1-carboxylate (75 mg).

Provenance & Evidence