Synthesis of eribulin mesylate

US11697655B2 · kind B2 · utility

Assignee

• WISDOM PHARMACEUTICAL CO., LTD · CN

Inventors

• Xiaolong Qiu · Nantong, CN
• Tao Xu · Suzhou, CN
• Zhiwei Zuo · Plainsboro, US
• Jie Ge · Nantong, CN
• Xinwei Lu · Nantong, CN
• Lingling Chu · Nantong, CN
• Wenbo Liu · Shanghai, CN
• Biao Wang · Lo Wu, CN
• Tingwei Gu · Nantong, CN
• Weiwei WANG · Beijing, CN
• Lin Hu · Nantong, CN
• Ping ZOU · Nantong, CN
• Jun Chen · Pleasanton, US
• Lei CAO · Dresden, DE

Key dates

• Filing date: Nov 5, 2021
• Grant date: Jul 11, 2023
• Expiry date: Mar 1, 2042

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07B2200/07
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A preparation method of an intermediate compound of formula II ((1R,2S,3S,4S,5S,6R,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxy]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-dimethylene-24,35,36,37,38,39-hexaoxane[29.3.1.13,6.14,34.111,14.117,21.023,27]nonatriacontan-8,29-dione) for eribulin mesylate is provided, including subjecting a compound of formula I to a reaction with an additive in the presence of tetra-n-butylammonium fluoride (TBAF). The additive is piperidine hydrochloride or pyridine hydrochloride, and a reaction formula is as follows:The present invention aims to avoid the problem that a traditional synthetic route has a low yield.