Two-Step Continuous Synthesis of Cabozantinib in a Microreactor: Mechanism and Kinetics Research of EDCI/HOBt-Mediated Amidation DOI
Qilin Xu,

Jingli Dai,

Fucheng Zhu

и другие.

Industrial & Engineering Chemistry Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Cabozantinib (CBT) is a small-molecule pharmaceutical approved for the treatment of medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. The two-step amidation starting with 1,1-cyclopropanedicarboxylic acid (CBT-1) large-scale synthetic route CBT, but existing processes suffered from highly toxic reagents, low yields, long reaction times. In this work, cascaded flow process was developed to synthesize CBT in microreactor. first step, CDI determined as coupling reagent generate 1-(4-fluorophenylaminoformyl) cyclopropane carboxylic (CBT-3) yield 97.5% after optimizing operating conditions. Then, EDCI/HOBt were screened reagents obtain second possible paths intrinsic kinetics revealed result indicated that formation ion pairs between CBT-3 EDCI rate-determining step whole process. end, two reactions microreactor, synthesized total 96.1% 35 min. scale-up microchemical system showed productivity can achieve about 5.3 g/h. Compared processes, milder reagents/conditions used, innovative approach continuous synthesis provide an efficient alternative method production CBT.

Язык: Английский

Continuous manufacturing based paradigm shift in pharmaceuticals production and current regulatory framework DOI

Kardile Punam Kashinath,

Lohare Rahul Sanjay,

Makka Krupali Ashokbhai

и другие.

Process Safety and Environmental Protection, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Combination of photocatalytic proton-coupled electron transfer and spin-center shift: direct C-H benzylation of N-heteroarenes with benzaldehydes in continuous-flow DOI

Jia-Cheng Hou,

Jun Jiang,

Hui Dai

и другие.

Science China Chemistry, Год журнала: 2025, Номер 68(5), С. 1945 - 1951

Опубликована: Фев. 24, 2025

Язык: Английский

Процитировано

0

Self-Optimizing Bayesian for Continuous Flow Synthesis Process DOI Creative Commons
Runzhe Liu, Zihao Wang, Wenbo Yang

и другие.

Digital Discovery, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

A Bayesian algorithm with self-optimizing capabilities, tailored for process optimization in continuous flow synthesis small datasets enhancing efficiency.

Язык: Английский

Процитировано

2

Enhancing Efficiency and Sustainability: Unleashing the Potential of Continuous Flow in Multicomponent Reactions DOI
Marcelo H. R. Carvalho, Pedro P. de Castro, Kléber T. de Oliveira

и другие.

ChemSusChem, Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

The integration of multicomponent reactions (MCRs), which offer a rapid and efficient approach to synthesize complex molecular scaffolds, with continuous flow platforms is an increasingly recognized strategy in green synthesis. This association enables precise control over reaction parameters, including improved kinetics selectivity, reduced times, enhanced yields scalabilities, while aligning sustainable chemistry principles through resource utilization, minimized waste, environmental impact. review presents critical analysis recent studies covering the MCR-continuous association, focus on achieving greener more synthesis practices.

Язык: Английский

Процитировано

2

Continuous‐Flow Photochemistry: The Synthesis of Marketed Pharmaceutical Compounds DOI
Vishal Srivastava, Praveen P. Singh, Surabhi Sinha

и другие.

ChemistrySelect, Год журнала: 2024, Номер 9(47)

Опубликована: Дек. 1, 2024

Abstract Chemistry professionals from all kinds of fields and disciplines in the academic commercial sectors have recently shown a great deal interest continuous‐flow chemistry. Flow methods are used nowadays for rapid optimization assessment, as well production scale‐up, reaction discovery, methodology. Photochemical processes currently receiving lot attention scientific community, application flow these approaches has advantages chemistry its importance modern industry worldwide. This study illustrates most recent advancements benefits continuous photochemical reactions relation to synthesis active pharmaceutical compounds recommended frameworks.

Язык: Английский

Процитировано

2

Photochemically Induced Approaches to the Syntheses of β‐Lactams DOI
Vijay Kumar Das, Imtiaz Ahmed, Nikita Gupta

и другие.

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(22), С. 4548 - 4558

Опубликована: Окт. 8, 2024

Abstract The synthesis of β‐lactam scaffolds is paramount importance due to their extensive applications in pharmaceuticals, particularly as antibiotics. Visible light photocatalysis has emerged a revolutionary approach this domain, providing sustainable and efficient pathway for construction. In review, we meticulously discuss the recent developments photocatalysed frameworks. A key focus Staudinger reaction, traditionally cornerstone synthesis, its adaptation visible photocatalysis. We explore mechanistic intricacies reaction under photochemical conditions, along with other pivotal cyclization strategies enabled by light. By illuminating novel photocatalytic routes β‐lactams, review provides thorough understanding state‐of‐the‐art techniques sets stage future innovations green these critical compounds.

Язык: Английский

Процитировано

1

Deep Neutral Network Enhanced Mesoscopic Thermodynamic Model for Unlocking the Electrode/Electrolyte Interface DOI Open Access
Haolan Tao, Sijie Wang, Honglai Liu

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Structure and properties of the electrode/electrolyte interface significantly influence electrochemical processes energy storage conversion, yet challenge lies in accurate description both molecular characteristics external field effects. Here, we develop a mesoscopic thermodynamic model that calculates electrolytes based on chemical potential, its efficiency is enhanced by deep neural network. The network (DeepMT) effectively bridges gap between micro-level ions macro-level effects field, enabling precise presentation ion density distributions over complex conditions. Our result indicates DeepMT not only demonstrates computational improvement approximately four orders magnitude direct theoretical calculations, but also accurately predicts including adsorption, surface charge, differential capacitance through statistical analysis distributions.

Язык: Английский

Процитировано

1

Batch and Continuous Flow Total Synthesis of Cannabidiol DOI
Kléber T. de Oliveira, Felipe C. Braga,

Felipe L. N. da Silva

и другие.

Chemistry - An Asian Journal, Год журнала: 2024, Номер 19(20)

Опубликована: Июль 23, 2024

Abstract Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the olivetolic acid derivatives utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring ( R )‐(+)‐limonene by photocatalysis. Key reactions, including ester Friedel‐Crafts alkylation, are successfully adapted flow, resulting in improved yields selectivities. This study not only offers scalable efficient route for but also contributes synthetic approaches access cannabinoids (diversity synthesis), with potential applications medicinal industrial contexts.

Язык: Английский

Процитировано

0

Deep Neutral Network Enhanced Mesoscopic Thermodynamic Model for Unlocking the Electrode/Electrolyte Interface DOI
Haolan Tao, Sijie Wang,

Honglai Liu

и другие.

Angewandte Chemie, Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract Structure and properties of the electrode/electrolyte interface significantly influence electrochemical processes energy storage conversion, yet challenge lies in accurate description both molecular characteristics external field effects. Here, we develop a mesoscopic thermodynamic model that calculates electrolytes based on chemical potential, its efficiency is enhanced by deep neural network. The network (DeepMT) effectively bridges gap between micro‐level ions macro‐level effects field, enabling precise presentation ion density distributions over complex conditions. Our result indicates DeepMT not only demonstrates computational improvement approximately four orders magnitude direct theoretical calculations, but also accurately predicts including adsorption, surface charge, differential capacitance through statistical analysis distributions.

Язык: Английский

Процитировано

0

Two-Step Continuous Synthesis of Cabozantinib in a Microreactor: Mechanism and Kinetics Research of EDCI/HOBt-Mediated Amidation DOI
Qilin Xu,

Jingli Dai,

Fucheng Zhu

и другие.

Industrial & Engineering Chemistry Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

Cabozantinib (CBT) is a small-molecule pharmaceutical approved for the treatment of medullary thyroid cancer, advanced renal cell carcinoma, and hepatocellular carcinoma. The two-step amidation starting with 1,1-cyclopropanedicarboxylic acid (CBT-1) large-scale synthetic route CBT, but existing processes suffered from highly toxic reagents, low yields, long reaction times. In this work, cascaded flow process was developed to synthesize CBT in microreactor. first step, CDI determined as coupling reagent generate 1-(4-fluorophenylaminoformyl) cyclopropane carboxylic (CBT-3) yield 97.5% after optimizing operating conditions. Then, EDCI/HOBt were screened reagents obtain second possible paths intrinsic kinetics revealed result indicated that formation ion pairs between CBT-3 EDCI rate-determining step whole process. end, two reactions microreactor, synthesized total 96.1% 35 min. scale-up microchemical system showed productivity can achieve about 5.3 g/h. Compared processes, milder reagents/conditions used, innovative approach continuous synthesis provide an efficient alternative method production CBT.

Язык: Английский

Процитировано

0