反应详情

温度

80 °C

To 1-isopropyl-4-(piperidine4-carbonyl)-piperazine (0.239 g)(D1) and 2-chloro-5-cyano-pyridine (0.138 g), dissolved in DMSO (5 ml), was added potassium carbonate (0.14 g). The reaction was heated to 80° C. for 4 h before cooling and dilution with saturated sodium hydrogen carbonate (50 ml) and EtOAc (80 ml). The EtOAc layer was washed further with brine (3×80 ml) and then extracted with 1N HCl. The aqueous HCl extract was basified and back-extracted with EtOAc which was concentrated under vacuum. A solution of 2N HCl in diethyl ether (1 ml) was then added and the precipitate filtered and washed with diethyl ether. Crystallisation from methanol afforded the title compound (E1)(0.15 g). 1H NMR δ [DMSO-d6]:1.29 (6H, d, J=6.4 Hz), 1.4-1.6 (2H, m), 1.7-1.85 (2H, m), 2.8-3.27 (6H, m), 3.32-3.62 (3H, m), 3.69 (1H, m), 4.24 (1H, brd, J=13 Hz), 4.35-4.55 (3H, m), 6.96 (1H, d, J=9.1 Hz), 7.84 (1H, dd, J=9.1Hz and 1.5 Hz), 8.47 (1H, d, J=1.5 Hz) and 11.36 (1H, brs). MS electrospray; (+ve ion) 342 (MH+).

1. temperaturebefore cooling
2. washThe EtOAc layer was washed further with brine (3×80 ml)
3. extractionextracted with 1N HCl
4. extractionThe aqueous HCl extract
5. extractionback-extracted with EtOAc which
6. concentrationwas concentrated under vacuum
7. additionA solution of 2N HCl in diethyl ether (1 ml) was then added
8. filtrationthe precipitate filtered
9. washwashed with diethyl ether
10. customCrystallisation from methanol