Isobutyronitrile → HCID 178448868, compound

Participants

Reaction Steps

Dibromobis(tri-tert-butylphosphine)dipalladium(I) (0.031 g, 0.040 mmol) was sealed in a microwave vessel under argon. Diisopropylamine (0.200 ml, 1.427 mmol) was added and the mixture cooled in a dry ice bath. A nitrogen needle was added followed by dropwise addition of butyllithium solution (2.5 m in hexanes, 0.500 ml, 1.250 mmol). The mixture was stirred for 5 minutes then isobutyronitrile (0.100 ml, 1.114 mmol) was added. The reaction was removed from the cold bath and allowed to slowly warm to room temperature. A solution of trans-N1-(benzo[d]thiazol-2-yl)-N3-(3-chloropyrazin-2-yl)cyclobutane-1,3-diamine (intermediate 27, 0.150 g, 0.452 mmol) in dry, sparged dioxane (1.5 mL) was added and the nitrogen needle removed. The reaction was heated at 95° C. for 14 hours. The crude was partitioned between water (100 mL), saturated ammonium chloride (10 mL) and ethyl acetate (200 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired 2-(3-((trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)amino)pyrazin-2-yl)-2-methylpropanenitrile (0.067 g, 0.184 mmol, 40.7% yield).

Provenance & Evidence