Reaction Steps
4-(3-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyrazinedicarboxylic acid, dimethyl ester (150 mg, 0.47 mmol) was slowly added into a mixture of 1,1′-carbonyidiimidazole (117 mg, 0.72 mmol) and triethylamine (145 mg, 1.44 mmol) in 5 mL of DMF and the reaction mixture was stirred for 60 min. 4-(3-Methoxyphenyl)piperidine-1-propanamine (176 mg, 0.69 mmol) was added to the reaction mixture, and the reaction was stirred at room temperature for 30 min. DMF was removed in vacuo and the residue was purified by chromatography (on silica gel, 10% (v/v) methanol in methylene chloride then followed by 2M ammonia in methanol) to give the title compound as an orange foam (200 mg, 72%); 1H-NMR (CDCl3) δ 7.55 (br, 1H), 7.35 (br, 1H), 7.20 (t, 1H, J=7.6 Hz), 6.92 (t, 1H, J=8.1 Hz), 6.60-6.80 (m, 4H), 6.54 (d, 1H, J=7.6 Hz), 6.32 (dd, 1H, J=8.2, 2.0 Hz), 5.99 (br, 1H), 3.77 (s, 3H), 3.71 (s, 6H), 3.16 (m, 2H), 3.03 (m, 2H), 2.46 (m, 3H), 2.29 (s, 6H), 1.95-2.20 (m, 2H), 1.60-1.90 (m, 6H); 13C-NMR (CDCl3) δ 166.6, 159.7, 156.8, 151.9, 149.7, 147.4, 139.4, 129.5, 129.2, 119.3, 112.9, 111.4, 108.9, 108.5, 106.1, 56.0, 55.2, 54.1, 51.7, 42.2, 38.6, 32.8, 26.8, and 17.6.
