反应详情

(R)-tert-Butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate (87, 950 mg, 2.8 mmol) was treated with 2:1 DCM/TFA (20 mL/10 mL) at RT for 20 min. The mixture was concentrated in vacuo to dryness as crude (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile (221, TFA salt). It was dissolved in 18 mL DMF. To it were added DIEA (3.9 mL, 22.4 mmol) and then the crude 520 (estimated 5.9 mmol) prepared. The mixture was stirred at RT for 1.5 hour, diluted with 120 mL EtOAc, washed with water and saturated NaHCO3 (aq) solution, dried, concentrated and subjected to silica flash column using 0 to 3.5% MeOH in DCM to isolate (R)-1-(3-chloro-5-(trifluoromethyl)phenyl)-3-(1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-yl)-1-methylurea (521) in quantitative yield.

1. concentrationThe mixture was concentrated in vacuo to dryness as crude (R)-5-(3-aminopiperidin-1-yl)-3-chloropyrazine-2-carbonitrile (221, TFA salt)
2. dissolutionIt was dissolved in 18 mL DMF
3. customthe crude 520 (estimated 5.9 mmol) prepared
4. washwashed with water and saturated NaHCO3 (aq) solution
5. customdried
6. concentrationconcentrated