1,2-Dichloroethane → 1-[2-(4-Amino-3-chloro-benzoylamino)-propionyl]-pyrrolidine-2-carboxylic acid (5-oxo-2-phenethyloxy-tetrahydro-furan-3-yl)-amide

Beteiligte Stoffe

Reaktionsschritte

To a solution of (5-oxo-2-phenethyloxy-tetrahydro-furan-3-yl)-carbamic acid allyl ester (194 mg, 0.54 mmol) (prepared as described for (40) using phenethyl alcohol) in anhydrous CH2Cl2 (5 mL) at 0° C. was added DMBA (196 mg, 1.26 mmol) and Pd(PPh3)4 (32 mg, 0.03 mmol). The solution was stirred for 15 min and a solution of 97a (prepared from 96a by treatment with TFA in CH2Cl2) (166 mg, 0.49 mmol) and DIEA (680 μl, 3.90 mmol) in CH2Cl2 (2 mL) was added followed by HOBT (98 mg, 0.73 mmol) and EDC (122 mg, 0.63 mmol). The solution was stirred at 0° C. for 15 min then at room temperature for 18 hours. The solvent was removed in vacuo and the residue dissolved in EtOAc then washed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine. Dried over anhydrous Na2SO4 and evaporated to give an orange solid which was purified by flash column chromatography, using CH2Cl2/MeOH (99/1 to 97/3%) to yield the title compound as a white solid (190 mg, 73% yield). 1H-NMR (500 MHz, CD3OD) δ 1.29 (d, 0.6H), 1.41 (d, 2.4H), 1.78 (m, 1H), 2.08 (m, 3H), 2.56 (m, 1H), 2.77 (dd, 1H), 2.94 (t, 2H), 3.53 (m, 0.3H), 3.67 (m, 0.8H), 3.85 (m, 2H), 3.96-4.08 (m, 1H), 4.40 (m, 2H), 4.62 (m, 1H), 4.67-4.79 (m, 1H), 5.57 (d, 0.7H), 5.60 (d, 0.3H), 6.78 (dd, 1H), 7.21 (m, 5H), 7.58 (m, 1H), 7.79 (m, 1H), 8.26 (d, 1H). Analytical HPLC 14.52 min. LC-MS (ES+) m/e=543.2 (MH+).

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