Optimization and Development of a Scalable Palladium-Catalyzed C-H Activation Process for the Geometry-Selective Preparation of Kilograms of YLF466D, a Potent AMP-Activated Protein Kinase Activator

doi:10.1021/acs.oprd.1c00150

	Optimization and Development of a Scalable Palladium-Catalyzed C-H Activation Process for the Geometry-Selective Preparation of Kilograms of YLF466D, a Potent AMP-Activated Protein Kinase Activator
	Yin, Jianpeng 1; Zhan, Desheng 1; Ma, Hui 2; Liu, Huanan 2; Yu, Lifang 2; Zhang, Yangming 1,2; Nan, Fajun 1,2,3
刊名	ORGANIC PROCESS RESEARCH & DEVELOPMENT
	2021-10-15
卷号	25 期号:10 页码:2260-2269
关键词	YLF466D AMPK activator glucose metabolism lipid metabolism MIRI domino reaction C-H activation
ISSN号	1083-6160
DOI	10.1021/acs.oprd.1c00150
通讯作者	Zhang, Yangming(ymzhang@simm.ac.cn) ; Nan, Fajun(fjnan@simm.ac.cn)
英文摘要	Adenosine 5'-monophosphate-activated protein kinase (AMPK) activator YLF466D is a promising preclinical drug candidate to treat metabolic diseases and myocardial ischemia-reperfusion injury (MIRI). Herein, we report our efforts on optimization and development of a practical and scalable process for the preparation of YLF466D in kilogram scale. The process features a palladium-catalyzed C-H activation under mild reaction conditions, geometry selectivity, effective impurities purging, and low levels of residual solvents in the final active pharmaceutical ingredient (API). We applied this process successfully to prepare more than 17 kg (3.0-3.6 kg per batch) of YLF466D to support its preclinical study.
资助项目	National Science and Technology Major Project[2018ZX09711002-012-005]
WOS关键词	ISCHEMIA
WOS研究方向	Chemistry
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000709699500009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298759]
专题	中国科学院上海药物研究所
通讯作者	Zhang, Yangming; Nan, Fajun
作者单位	1.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Yin, Jianpeng,Zhan, Desheng,Ma, Hui,et al. Optimization and Development of a Scalable Palladium-Catalyzed C-H Activation Process for the Geometry-Selective Preparation of Kilograms of YLF466D, a Potent AMP-Activated Protein Kinase Activator[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT,2021,25(10):2260-2269.
APA	Yin, Jianpeng.,Zhan, Desheng.,Ma, Hui.,Liu, Huanan.,Yu, Lifang.,...&Nan, Fajun.(2021).Optimization and Development of a Scalable Palladium-Catalyzed C-H Activation Process for the Geometry-Selective Preparation of Kilograms of YLF466D, a Potent AMP-Activated Protein Kinase Activator.ORGANIC PROCESS RESEARCH & DEVELOPMENT,25(10),2260-2269.
MLA	Yin, Jianpeng,et al."Optimization and Development of a Scalable Palladium-Catalyzed C-H Activation Process for the Geometry-Selective Preparation of Kilograms of YLF466D, a Potent AMP-Activated Protein Kinase Activator".ORGANIC PROCESS RESEARCH & DEVELOPMENT 25.10(2021):2260-2269.