反应详情

温度

165 °C

A mixture of 2,5-dichloropyridine (10.0 g, 67.6 mmol) and piperazine (58.1 g, 675 mmol) was stirred at 165° C. for 2 h. The mixture was allowed to cool, slurried with dichloromethane (200 ml) and the solid collected by filtration. The filtrate was concentrated in vacuo and the procedure repeated. The residue after concentration of the filtrate was purified by flash chromatography twice (eluting with 1% ammonia, 10% methanol in dichloromethane) to give 1-(5-chloro-2-pyridyl)piperazine (12.25 g, 92%) as a tan solid. A portion of this solid (0.484 g, 2.45 mmol) was added to a solution of 3-dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (0.392 g, 2.24 mmol) in toluene (10 ml) and the mixture heated at reflux under nitrogen for 6 h. The mixture was allowed to cool and the crystallised product filtered off. Recrystallisation from toluene gave the title compound (0.229 g, 31%), m.p. 196°-198° C.; (Found: C, 63.16; H, 5.60; N, 21.18. C17H18ClN5. 0.1 PhMe requires C, 63.08; H, 5.62; N, 20.78%); δH (DMSO-d6) 2.46 (4H, t, J 5.0 Hz, 2×piperazinyl CH2), 3.45 (4H, t, J 5.0 Hz, 2×piperazinyl CH2), 3.67 (2H, s, CH2N), 6.82 (1H, d, J 9.1 Hz, 3'-H), 7.04 (1H, dd, J 7.8, 4.6 Hz, 5-H), 7.37 (1H, d, J 2.1 Hz, 2-H), 7.56 (1H, dd, J 9.1, 2.7 Hz, 4'-H), 8.05 (1H, dd, J 7.8, 1.4 Hz, 4-H), 8.08 (1H, d, J 2.7 Hz, 6'-H), 8.19 (1H, dd, J 4.6, 1.4 Hz, 6-H), and 11.46 (1H, br s, NH); m/z (CI+, NH3) 328 [(M+H)+, 35Cl].

1. temperatureto cool
2. filtrationthe solid collected by filtration
3. concentrationThe filtrate was concentrated in vacuo
4. customThe residue after concentration of the filtrate was purified by flash chromatography twice (eluting with 1% ammonia, 10% methanol in dichloromethane)