One pot synthesis of tetrazole derivatives of sirolimus

ONE POT SYNTHESIS OF TETRAZOLE DERIVATIVES OF SIROLIMUS 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...

Full description

Saved in:
Bibliographic Details
Main Authors CHEN, YOUNG, BURKAR, SANJAY, BONK, PETER, PATEL, SUBHASH, HSIAO, CHU-NUNG, DHAON, MADHUP
Format Patent
LanguageEnglish
Published 23.01.2014
Subjects
CHEMISTRY
HETEROCYCLIC COMPOUNDS
HUMAN NECESSITIES
HYGIENE
MEDICAL OR VETERINARY SCIENCE
METALLURGY
ORGANIC CHEMISTRY
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
Online AccessGet full text

Cover

More Information
Summary:ONE POT SYNTHESIS OF TETRAZOLE DERIVATIVES OF SIROLIMUS 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.
Bibliography:Application Number: AU20140200017