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

Jianpeng Yin; Desheng Zhan; Hui Ma; Huanan Liu; Lifang Yu; Yangming Zhang; Fajun Nan

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

Jianpeng Yin
, Desheng Zhan
, Hui Ma
, Huanan Liu
, Lifang Yu
, Yangming Zhang^*
, Fajun Nan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2260-2269
Number of pages	10
Journal	Organic Process Research and Development
Volume	25
Issue number	10
DOIs	https://doi.org/10.1021/acs.oprd.1c00150
State	Published - 15 Oct 2021
Externally published	Yes

Keywords

AMPK activator
C-H activation
MIRI
YLF466D
domino reaction
glucose metabolism
lipid metabolism

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10.1021/acs.oprd.1c00150

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Yin, J., Zhan, D., Ma, H., Liu, H., Yu, L., Zhang, Y., & Nan, F. (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 and Development, 25(10), 2260-2269. https://doi.org/10.1021/acs.oprd.1c00150

@article{e50548c974ed47978c77dcbe31fa08fe,

title = "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",

abstract = "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.",

keywords = "AMPK activator, C-H activation, MIRI, YLF466D, domino reaction, glucose metabolism, lipid metabolism",

author = "Jianpeng Yin and Desheng Zhan and Hui Ma and Huanan Liu and Lifang Yu and Yangming Zhang and Fajun Nan",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = oct,

day = "15",

doi = "10.1021/acs.oprd.1c00150",

language = "英语",

volume = "25",

pages = "2260--2269",

journal = "Organic Process Research and Development",

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Yin, J, Zhan, D, Ma, H, Liu, H, Yu, L, Zhang, Y & Nan, F 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 and Development, vol. 25, no. 10, pp. 2260-2269. https://doi.org/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; Zhan, Desheng; Ma, Hui et al.
In: Organic Process Research and Development, Vol. 25, No. 10, 15.10.2021, p. 2260-2269.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Yin, Jianpeng

AU - Zhan, Desheng

AU - Ma, Hui

AU - Liu, Huanan

AU - Yu, Lifang

AU - Zhang, Yangming

AU - Nan, Fajun

PY - 2021/10/15

Y1 - 2021/10/15

N2 - 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.

AB - 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.

KW - AMPK activator

KW - C-H activation

KW - MIRI

KW - YLF466D

KW - domino reaction

KW - glucose metabolism

KW - lipid metabolism

UR - https://www.scopus.com/pages/publications/85117176844

U2 - 10.1021/acs.oprd.1c00150

DO - 10.1021/acs.oprd.1c00150

M3 - 文章

AN - SCOPUS:85117176844

SN - 1083-6160

VL - 25

SP - 2260

EP - 2269

JO - Organic Process Research and Development

JF - Organic Process Research and Development

IS - 10

ER -

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

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