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With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; N,N-dimethyl-formamide; for 8h; |
Synthesis of 1-155 Compound 1-153 (1.14 g, 3.44 mmol), compound 4444 (N-9-fluorenylmethoxycarbonylglutamic acid alpha-methyl ester, commercially available) (1.72 g, 4.47 mmol), and HBTU (1.96 g, 5.16 mmol) were dissolved in 50 mL of DCM:DMF (8:2). DIEA (1.78 g, 13.8 mmol) was added and the reaction stirred for 8 h. The volatiles were removed in vacuo and the residue was dissolved in DCM and extracted with sat. NH4Cl (2×), sat. NaHCO3 (2×) and water (2×). The organic layer was dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel chromatography (8:2, EtOAc:Hex) to give 1-155. 1H NMR (CDCl3, 500 MHz) delta 7.79-7.05 (m, 15H), 6.59 (d, J=7.5 Hz, 1H), 5.81 (br s, 1H), 5.78 (d, J=5 Hz, 1H), 5.17 (d, J=13.5 Hz, 1H), 5.08 (m, 1H), 4.35-4.2 (m, 3H), 4.17 (m, 1H), 3.69-2.85 (diastereomeric Me, 9H), 2.15 (br m, 2H), 1.99-1.89 (m, 2H). 13C NMR (CDCl3, 100 MHz) delta 172.5, 169.9, 156.4, 146.5, 145.3, 143.93, 143.91, 143.8, 143.4, 141.4, 136.0, 135.8, 129.0, 128.6, 127.8, 127.22, 127.20, 127.17, 125.3, 125.23, 125.20, 124.9, 120.7, 120.12, 120.11, 120.05, 119.9, 119.5, 117.2, 113.3, 112.8, 112.7, 105.4, 72.5, 66.94, 66.91, 53.6, 53.5, 52.7, 50.0, 47.3, 44.5, 33.4, 33.3, 32.2, 28.5, 28.4. HRMS (ESI) calcd. for C41H41BN4O6 [M+H] 696.3229, found 696.3253. |