Reaction Steps
To a solution of 3-aminopyridazine (62 mg, 0.65 mmol) (Wermuth, C.-G. J. Het. Chem. 1998, 35, 1091-1100) in CH2Cl2 (5 mL) was added 1,1′carbonyldiimidazole (128 mg, 0.79 mmol). After stirring at room temperature for 1.5 h, the mixture was heated to 50° C. After 45 min, (3,5-dimethyl-pyridin-2-ylmethyl)-(3-isopropyl-pyridin-2-ylmethyl)-piperidine-4-yl-amine (115 mg, 0.33 mmol) was added and stirring was continued for 50° C. After 2 h, the reaction mixture was cooled, diluted with CH2Cl2 (20 mL), and washed with saturated NaHCO3 (3×20 mL). The organic layer was dried (MgSO4), filtered, and concentrated to afford a pale yellow oil. Purification by radial chromatography on silica gel (1 mm plate; using CH2Cl2/MeOH/NH4OH; 50:1:1) afforded COMPOUND 315 as a pale yellow oil (44 mg, 28%). 1H NMR (CDCl3) δ 0.93 (d, 6H, J=6.0 Hz), 1.64-1.75 (m, 2H), 1.96-1.99 (m, 2H), 2.16 (s, 3H), 2.28 (s, 3H), 2.75-2.84 (m, 4H), 3.78 (s, 2H), 3.84 (s, 2H), 4.21 (s, 1H), 4.26 (s, 1H), 7.15-7.17 (m, 1H), 7.38-7.42 (m, 1H), 7.50 (dd, 1H, J=6.0, 3.0 Hz), 7.99 (s, 1H), 8.18 (s, 1H), 8.32 (d, 1H, J=3.0 Hz), 8.33 (d, 1H, J=3.0 Hz), 8.80 (s, 1H). 13C NMR δ 18.30, 18.46, 23.61, 27.46, 44.89, 53.83, 54.34, 57.27, 118.83, 123.22, 128.28, 132.33, 133.19, 133.88, 139.08, 144.40, 146.12, 146.70, 147.89, 153.74, 154.38, 156.21, 156.96. ES-MS m/z 496 [M+H]+. Anal. Calcd. for C27H35N7O.1.4CH2Cl2.0.5H2O: C, 56.71; H, 6.50; N, 16.30. Found: C, 56.48; H, 6.32; N, 16.54.
