Reaction Steps
A mixture of 3 (196 mg; 1.0 mmol) and N-Fmoc-3-iodopropylamine (1.22 g; 3.0 mmol) in MeCN (40 ml) was heated at reflux for 4.5 days. When compound 3, urea derivative, was not detectable by TLC, the reaction mixture was concentrated in vacuo, resulting in a white solid. The solid material was redissolved in MeCN (40 ml) and 2-trimethylsilylethanol (355 mg; 3.0 mmol) and dipea (259 mg; 2.0 mmol) were added. The resulting mixture was stirred at RT under N2 for 16 hrs. The solvent was removed in vacuo, followed by purification by column chromatography (silica; EtOAc). Yield: 316 mg (53% over two steps) of a foamy colourless solid Found: C, 62.1; H, 6.2; N, 9.5; Calc. for C31H40N4O6Si: C, 62.8; H, 6.8; N, 9.5; νmax (KBr)/cm−1 3329br NH, 1730s, 1698vs C═O; δH (300.8 MHz; CD3CN) 7.82 (2H, pseudo-d, 2×ArH), 7.64 (2H, pseudo-d, 2×ArH), 7.38 (3H, m, 2×ArH+N2CHHis), 7.32 (2H, pseudo-t, 2×ArH), 6.79 (1H, s, CHHis), 6.55 (1H, d, J 7.5, NH), 5.68 (1H, br s, NH), 4.35 (3H, overlapping m, OCH2−Fmoc+CαH), 4.22 (1H, t, J 6.6, OCH2CH−Fmoc), 4.07 (2H, m, CH2), 3.87 (2H, m, CH2), 3.60 (3H, s, OCH3), 2.99 (2H, m, CH2), 2.90 (2H, m, CβH2), 1.85 (2H, m, CH2), 0.93 (2H, m, CH2), 0.01 (s, 9H, Si—(CH3)3). δC (CD3CN; 75.47 MHz) 173.7 (C═Oester), 157.7, 157.6 (2×C═Oamide), 145.5, 142.2 (2×ArCq), 138.4 (CHis), 128.9, 128.3 (2×ArCH), 126.4 (CHis), 121.2, 118.6 (2×ArCH), 118.1 (CHis), 66.9, 63.7, 55.3, 52.7, 48.3, 44.9, 38.6, 32.1, 30.1, 18.3, 1.4 (Si(CH3)3); m/z (ESI-pos., MeOH) 343, 371, 533, 593 [M+H]+.
