| 摘要 |
<P>PROBLEM TO BE SOLVED: To provide a single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale. <P>SOLUTION: Dried rapamycin is dissolved in isopropylacetate. After cooling and 2,6-lutidine addition, triflic anhydride is slowly added at -30°C. Salts are 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 an eluant. The product is collected, concentrated, and purified 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 and treated with butylated-hydroxy toluene, and the solution is 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 |
