Title:
PROCESS FOR PREPARATION OF GLUCURONIDE DRUG-LINKERS AND INTERMEDIATES THEREOF
Document Type and Number:
Japanese Patent JP2023105175
Kind Code:
A
Abstract:
To provide methods for treatment of diseases.SOLUTION: The invention provides improved processes for preparation of drug-linkers with a β-glucuronide cleavable unit, and intermediates thereof. The present invention is based, in part, on the surprising discovery that a method of deprotection of a glucuronide unit in synthesis of certain drug linker compounds can have a profound effect on the purity and yield of a desired product. Specifically, the present inventors have discovered that using an alkoxymagnesium halide in a solvent comprising an alcohol for removal of acyl protecting groups in a carbohydrate moiety of the glucuronide unit, instead of conventionally used reagents such as LiOH, leads to significant reduction of an undesirable β-eliminated impurities (to below about 5% from about 20%). In some aspects, the alkoxymagnesium halide reagent is prepared in situ by contacting a Grignard reagent with the alcohol-containing solvent.SELECTED DRAWING: None
Inventors:
MAO YUNYU
PHILIP MOQUIST
ANUSUYA CHOUDHURY
WENDEL DOUBLEDAY
PHILIP MOQUIST
ANUSUYA CHOUDHURY
WENDEL DOUBLEDAY
Application Number:
JP2023094226A
Publication Date:
July 28, 2023
Filing Date:
June 07, 2023
Export Citation:
Assignee:
SGEN INC
International Classes:
C07H15/203; C07H1/00
Attorney, Agent or Firm:
Shusaku Yamamoto
Natsuki Morishita
Natsuki Morishita
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