Chemburkar, Sanjay,Hsiao, Chu-Nung,Patel, Subhash,Bonk, Peter,Dhaon, Madhup,Chen, Young
申请号：
AU2006338175
公开号：
AU2006338175B2
申请日:
2006.12.12
申请国别(地区):
AU
年份:
2013
代理人:
摘要：
A single-step, one-pot process to obtain zotarolimus and other rapamycin derivatives on large scale that improves currently available syntheses. In one embodiment, 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 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, treated with butylated-hydroxy toluene, 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.
