化学合成。
化学合成
合成路线 1（1. 合成：31827-94-8）
产率：100%
合成条件：With bromine In 1,4-dioxane at 20℃; for 1 h;
实验步骤：在冰浴上向对 - 碘代苯乙酮1（30.0g，122mmol）的二恶烷（200mL）搅拌溶液中逐滴加入溴（6.56mL，128mmol）。将反应混合物在室温下搅拌并通过LC / MS监测。完成后（约1小时），通过旋转蒸发法蒸发溶剂，并将残余物在真空下干燥，得到固体2（40g，100％）。 （基于J.Med.Chent.2001,44,2990-3000）向Cbz-D-Ala-OH 3（5.0g，22.4mmol）在NMP（100mL）中的溶液中加入碳酸铯（ 3.72克，11.4毫摩尔）。在室温下搅拌1小时后，加入2（7.60g，22.4mmol）。将反应混合物在室温下搅拌并通过LC / MS监测以形成4.将反应溶液用二甲苯（100mL）和乙酸铵（9.25g，120mmol）稀释，然后在120℃下搅拌4小时。根据反应进程，可能需要高达50当量的额外乙酸铵。关键是始终在烧瓶中看到固体。冷却至室温后，将反应混合物用乙酸乙酯（200mL）稀释。将EtOAc溶液用饱和碳酸氢钠溶液（200mL）洗涤两次，并用硫酸钠干燥，然后过滤，并将滤液减压浓缩。将残余物溶于DCM（100mL）中并搅拌1小时，得到沉淀，滤出固体5（4.0g）并真空干燥。通过旋转蒸发仪浓缩母液，将残余物在Bio-tage上纯化，得到5（己烷：EtOAc = 1：1至EtOAc，100％）。合并两种产物并在真空下干燥，得到5（5.8g，58％）。
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