| 摘要 |
<P>PROBLEM TO BE SOLVED: To provide a one-pot synthesizing process to obtain zotarolimus and other rapamycin derivatives on large scale. <P>SOLUTION: A dried rapamycin is dissolved in isopropyl acetate. The solution is cooled, and 2,6-Lutidine is added, followed by slowly adding trifluoromethanesulfonic anhydride at -30°C. Salts are then removed by filtration. Tetrazole, followed by a tert-base diisopropylethylamine is added. After incubation at room temperature, the product is concentrated and purified by a silica gel column using THF/heptane as eluant. The fractions containing the product are collected, concentrated, and purified again using an acetone/heptane column. The product containing fractions are concentrated. The product is dissolved in t-BME and precipitated with heptane. The solids are dissolved in acetone, treated with butylated-hydroxy toluene (BHT), and the solution concentrated. The process is repeated twice with acetone to remove solvents. At least one stabilizing agent is added, such as BHT at 0.5% before drying. <P>COPYRIGHT: (C)2013,JPO&INPIT |
