反应详情

温度

70 °C

A suspension of cis-4-(2-chloro-5-nitropyridin-4-ylamino)cyclohexanecarboxylic acid hydrochloride (0.5 g, 1.487 mmol) in thionyl chloride (10.86 mL, 149 mmol) was heated at 70° C. for 1.5 hours. The mixture was concentrated under reduced pressure and dried under high vacuum for 1 hour. The resulting solid was suspended in THF (14.87 mL) and cooled to 0° C. under nitrogen atmosphere. To this mixture was added (R)-tert-butyl 3-methylpiperazine-1-carboxylate (0.357 g, 1.785 mmol) as a solution in THF (5 mL). The ice bath was removed, and the reaction mixture was stirred overnight at RT. The resulting mixture was diluted with DCM (100 mL) and washed with saturated aqueous NaHCO3 solution (30 mL) and then with saturated aqueous ammonium chloride solution (2×). The organic phase was collected, dried over sodium sulfate, and concentrated under reduced pressure to afford (R)-tert-butyl 4-(cis-4-(2-chloro-5-nitropyridin-4-ylamino)cyclohexanecarbonyl)-3-methylpiperazine-1-carboxylate as a light yellow solid (0.55 g, 77% yield). MS m/z=482.2 [M+H]. Calc'd for C22H32ClN5O5: 481.2.

1. concentrationThe mixture was concentrated under reduced pressure
2. customdried under high vacuum for 1 hour
3. temperaturecooled to 0° C. under nitrogen atmosphere
4. customThe ice bath was removed
5. additionThe resulting mixture was diluted with DCM (100 mL)
6. washwashed with saturated aqueous NaHCO3 solution (30 mL)
7. customThe organic phase was collected
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated under reduced pressure