[Synthesis]
A 60% sodium hydride dispersion (4 g, 0.1 mol) was slowly added to a stirred solution of 3-amino-1-propanol (7.51 g, 0.1 mol) in tetrahydrofuran (THF, 150 mL) at room temperature. The reaction mixture was stirred under nitrogen protection for 30 min before benzyl bromide (11.9 mL, 0.1 mol) was added. The reaction was continued to be stirred at room temperature for 10 hours, followed by vacuum concentration. The concentrated residue was partitioned between a 1N aqueous hydrochloric acid solution and dichloromethane (CH2Cl2). The aqueous layer was adjusted to pH 10 with 10% aqueous sodium hydroxide and subsequently extracted with dichloromethane (3 x 100 mL). The organic phases were combined, dried with magnesium sulfate (MgSO4) and concentrated in vacuum. The residue was purified by silica gel column chromatography using dichloromethane/methanol (3:1 to 2:1, v/v) as eluent to give 3-(benzyloxy)propylamine (8.3% yield) as a yellow oil. A solution of 1,3-dicyclohexylcarbodiimide (14.4 mg, 0.07 mmol) in dichloromethane (2 mL) was added dropwise to a solution of compound 5 (32 mg, 0.07 mmol), 3-(benzyloxy)propylamine (0.07 mmol), and 1-hydroxybenzotriazole hydrate (9.5 mg, 0.07 mmol) in dichloromethane (5 mL) at 0°C . The reaction mixture was stirred at room temperature for 18 h and then concentrated under vacuum. The residue was purified by silica gel column chromatography using dichloromethane/methanol (30:1, v/v) as eluent to afford compound 8 (36 mg, 85% yield) as a light yellow liquid.1H NMR (CDCl3) δ 8.05 (s, 1H, H4), 7.44 (d, 1H, H5, J = 8.7Hz), 7.19-7.28 (m, 11H H6 + 2 × OCH2Ph), 6.78-6.82 (m, 3H, H2' + H5' + H6'), 6.06 (AB, 2H, 3',4'-OCH2O-, J = 6.9 Hz, J = 1.5 Hz), 5.84 (AB, 2H, 7,8-OCH2O-, J = 4.2 Hz, J = 1.5 Hz), 4.45 (s 4H, 2 × OCH2Ph), 4.38 (s, 2H, 2-CH2OBn), 3.55 (m, 4H, 3-CONHCH2CH2CH2OBn), 1.87 (quintuple peak, 2H, 3-CONHCH2CH2CH2OBn, J = 6.3 Hz); MS (FAB, positive) m/z 604 [M + H]+. |