反应详情

温度

70 °C

(R)-3-(1-(6-Chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1-methyl-1-phenylurea (513, 100 mg) was dissolved in 4 mL DMSO in a sealed tube. To it was added cyclopropylamine (210 μL, 3 mmol) and the mixture was stirred in 70° C. bath for 16 hours. It was diluted with 60 mL EtOAc, washed with water ×2, concentrated in vacuo to afford crude (R)-3-(1-(5-cyano-6-(cyclopropylamino)pyrazin-2-yl)piperidin-3-yl)-1-methyl-1-phenylurea (514). It was dissolved in 4 mL MeOH and 2 mL DMSO. To it were added one NaOH solid pellet (about 50-100 mg) and then 0.5 mL 30% H2O2. The mixture was stirred at RT for 45 min, diluted with 10 mL MeCN, stirred for 5 min, concentrated on rotavap. The residue was treated with 0.3 mL TFA, and directly subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate (R)-3-(cyclopropylamino)-5-(3-(3-methyl-3-phenylureido)piperidin-1-yl)pyrazine-2-carboxamide (515) as HCl salt (74 mg, 67% yield). LC-MS (ESI): m/z (M+1) 410.3. UV: λ=283, 317, 369 nm.

1. washwashed with water ×2
2. concentrationconcentrated in vacuo