Large-Scale Tandem Cyclization Applied to Potentially High-Volume SSTR4 Agonists

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-05-29 DOI:10.1021/acs.oprd.4c00144

Louise M. Guard, and , John R. Rizzo*,

引用次数: 0

Abstract

Somatostatin receptor subtype 4 (SSTR4) antagonists are potential clinical targets for pain. We describe the efforts toward a robust large-scale synthesis of certain small-molecule SSTR4 agonist compounds. Previous routes used metal-mediated reactions and produced stereochemical mixtures. The molecule has a 3-azabicyclo[3.1.0]hexane ring system with cis-stereochemistry. A unique tandem cyclization at the multi-kilogram scale was employed to generate the fused ring system with exclusive cis-stereochemistry observed. The potential commercial synthesis is an efficient, economical process with good control points. This novel tandem cyclization was implemented to swiftly scale up a similar compound for early-phase studies.

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大规模串联环化应用于潜在的高容量 SSTR4 激动剂

体生长抑素受体亚型 4 (SSTR4) 拮抗剂是治疗疼痛的潜在临床靶点。我们介绍了为大规模合成某些小分子 SSTR4 激动剂化合物所做的努力。以前的路线使用金属介导的反应并产生立体化学混合物。该分子具有顺式立体化学的 3-氮杂双环[3.1.0]己烷环系统。该化合物采用了独特的多千克级串联环化技术，生成了具有唯一顺式立体化学性质的融合环系统。这种潜在的商业合成是一种高效、经济的工艺，具有良好的控制点。采用这种新颖的串联环化方法，可以迅速扩大类似化合物的规模，以进行早期阶段的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.