반응 #82488
ord-c19fc05afc4f4b18949bc28d86a7ba8f
반응 조건
후처리
- 1온도to cool
- 2여과the solid collected by filtration
- 3농축The filtrate was concentrated in vacuo
- 4기타The residue after concentration of the filtrate was purified by flash chromatography twice (eluting with 1% ammonia, 10% methanol in dichloromethane)
실험 절차
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].