反应详情

(R)-tert-Butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate (87, 2.00 g, 5.93 mmol) was treated with 25 mL commercial 4N HCl in dioxane at RT for 2 hours. It was concentrated in vacuo to afford crude (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile (221) hydrochloride as white solid. It was dissolved in 10 mL DMF and 50 mL dioxane. To it were added DIEA (8.25 mL, 47.4 mmol) and then dropwise dimethylcarbamoyl chloride (1.64 mL, 17.8 mmol). The mixture was stirred at RT for 3 hours. It was concentrated in vacuo, diluted with 200 mL EtOAc, washed with water ×2, dried, concentrated in vacuo, subjected to silica flash column using 0 to 4% MeOH in DCM to isolate (R)-3-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1,1-dimethylurea (222) (1.47 g, 80%) as a white solid.

1. concentrationIt was concentrated in vacuo