[Synthesis]
General procedure for the synthesis of compound (CAS:863971-53-3) from bis(4-nitrophenyl) carbonate and compound (CAS:159858-22-7): under nitrogen protection, N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl-N5-carbamoyl-N-[4-(hydroxymethyl)phenyl]-L-ornithinamide ( 1.3 g, 2.16 mmol, prepared as reported in EP0624377A2) was dissolved in 6 mL of anhydrous DMF with bis(4-nitrophenyl) carbonate (1.32 g, 4.34 mmol). After addition of DIPEA (0.75 mL, 4.35 mmol), the reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, diethyl ether (120 mL) was added to precipitate the product, and the precipitate was collected by filtration, washed with diethyl ether, and dried under vacuum to afford N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl-N5-carbamoyl-N-[4-({{[(4-nitrophenoxy)carbonyl]oxy}methyl)phenyl]-L-ornithinamide (1.47 g, yield 89%). ESI MS: m/z 767 (MH+). 1H NMR (400MHz, DMSO-d6) δ 0.86 (d, J=6.7Hz, 3H), 0.88 (d, J=6.7Hz, 3H), 1.30-1.52 (m, 2H), 1.60 (m, 1H), 1.69 (m, 1H), 1.99 (m, 1H ), 2.90-3.10 (m, 2H), 3.93 (dd, J=8.9,7.0Hz, 1H), 4.14-4.34 (m, 3H), 4.42 (m, 1H), 5.24 (s, 2H), 5.39 (s, 2H), 5.97 (t, J=5.5Hz, 1H), 7.32 (m, 2H), 7.42 (m, 5H ), 7.55 (m, 2H), 7.65 (d, J=8.4Hz, 2H), 7.74 (t, J=7.9Hz, 2H), 7.88 (d, J=7.6Hz, 2H), 8.12 (d, J=7.4Hz, 1H), 8.31 (m, 2H), 10.12 (s, 1H). |