反应详情

1-Isopropyl-4-(pipeddine-4-carbonyl)-piperazine (D1)(0.116 g), 4-chloro-2-cyanopyridine (T. Sakamoto, S-I. Kaneda, S. Nishimura and H. Yamanaka, Chem. Pharm. Bull., 1985, 33(2), 565-571)(0.2 g) and anhydrous potassium carbonate (0.347 g) were heated in dry DMSO at 150° C. with stirring, under argon, for 2 h. The cooled mixture was diluted with methanol and applied to an SCX resin column. The column was eluted initially with methanol and then with methanolic ammonia (2M). The ammoniacal eluates were concentrated and the resulting gum was further purified by silica gel chromatography eluting with 0-10% methanolic ammonia (2M) in DCM. The free-base thus obtained was dissolved in DCM (5 ml) and treated with ethereal HCl (1.0M, 5 ml). The resulting suspension was evaporated to dryness by blowing down with a gentle stream of argon, to give the title compound (E98) as an off-white solid (0.117 g). 1H NMR δ [DMSO-d6]: 1.29 (6H, d, J=7 Hz), 1.48-1.63 (2H, m), 1.75 (2H, m), 2.89 (1H, br. m), 3.02-3.14 (5H, m), 3.38 (2H, m), 3.47 (1H, m), 3.65 (1H, m), 4.11 (2H, br. m), 4.24 (1H, br. d, J≈14 Hz), 4.48 (1H, br. d, J≈14 Hz), 7.15 (1H, dd, J=7,3 Hz), 7.65(1H, d, J=3 Hz), 8.26 (1H, d, J=7 Hz), 11.10 (1H, br.); LCMS electrospray (+ve) 342 (MH+).

1. washThe column was eluted initially with methanol
2. concentrationThe ammoniacal eluates were concentrated
3. customthe resulting gum was further purified by silica gel chromatography
4. washeluting with 0-10% methanolic ammonia (2M) in DCM
5. customThe free-base thus obtained
6. customThe resulting suspension was evaporated to dryness