Practical Synthesis of Reactive Immuno-PET Linker-Chelator (1R,2R)-RESCA-TFP

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2023-06-28 DOI:10.1021/acs.oprd.3c00149

Nicholas Wong, Eileen Zhao, Jiangyin Bao, Stefan G. Koenig, Carmela Molinaro, Jacob C. Timmerman, Haiming Zhang*, C. Gregory Sowell and Francis Gosselin,

引用次数: 0

Abstract

We herein report the evolution of decagram syntheses of a single enantiomer of immuno-PET linker-chelator (1R,2R)-RESCA-TFP (1) from commercially available (1R,2R)-1,2-diaminocyclohexane. The syntheses feature a reductive amination, a trialkylation, a saponification followed by EDCI-promoted TFP ester formation, and finally a t-Bu ester global deprotection. While the first-generation synthesis required chromatographic purification of process intermediates and 1, the second-generation synthesis implemented salt formation and direct isolation by filtration, thus eliminating all preparative purification operations.

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反应性免疫- pet连接-螯合剂(1R,2R)-RESCA-TFP的实用合成

本文报道了从市售的(1R,2R)-1,2-二氨基环己烷中合成免疫- pet连接-螯合剂(1R,2R)-RESCA-TFP(1)单对映体的演化过程。合成的特点是还原胺化，三烷基化，皂化，其次是edci促进的TFP酯形成，最后是t-Bu酯全局去保护。第一代合成方法需要对工艺中间体和1进行色谱纯化，而第二代合成方法通过过滤形成盐并直接分离，从而消除了所有制备纯化操作。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.

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