Process to convert technical ascomycin into purified pimecrolimus

US10975097B2 · kind B2 · utility

Assignee

• MEDA AB · SE

Inventors

• Borut Gabriel · Borovnica, SI
• Alja{hacek over (z)} Kajtna · Ljubljana, SI
• Ajna Lukic · Šmarje-Sap, SI
• Dominic De Souza · Regau, AT
• Werner Hasselwander · Oberkirch, DE

Key dates

• Filing date: May 2, 2018
• Grant date: Apr 13, 2021
• Expiry date: May 2, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07B2200/13
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present disclosure is directed to an improved process to convert crude ascomycin to purified pimecrolimus. Crude ascomycin is chlorinated with triphenylphosphine and N-chlorosuccinimide (NCS) to yield crude pimecrolimus, which is then purified further by HPLC and subsequent crystallization. The processes of the present disclosure enable the removal of close homologs of pimecrolimus by high-pressure liquid chromatography without prior purification of the ascomycin starting material. This improvement may make the conversion of ascomycin to pimecrolimus industrially applicable and less expensive.