Development of a Practical Manufacturing Process to Relebactam via Thorough Understanding of the Origin and Control of Oligomeric Impurities

被引：2

作者：

Kim, Jungchul ^{[1
]}

Itoh, Tetsuji ^{[1
]}

Xu, Feng ^{[1
]}

Dance, Zachary E. X. ^{[1
]}

Waldman, Jacob H. ^{[1
]}

Wallace, Debra J. ^{[1
]}

Wu, Feiyue ^{[1
]}

Kats-Kagan, Roman ^{[1
]}

Ekkati, Anil R. ^{[1
]}

Brunskill, Andrew P. J. ^{[1
]}

Peng, Feng ^{[1
]}

Fier, Patrick S. ^{[1
]}

Obligacion, Jennifer, V ^{[1
]}

Sherry, Benjamin D. ^{[1
]}

Liu, Zhijian ^{[1
]}

Emerson, Khateeta M. ^{[1
]}

Fine, Adam J. ^{[1
]}

Jenks, Anna, V ^{[1
]}

Armenante, Marco Euclide ^{[2
]}

机构：

[1] Merck & Co Inc, MRL, Proc Res & Dev, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Chem Commercializat Technol, Rahway, NJ 07065 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2021年 / 25卷 / 10期

关键词：

relebactam; oligomers; hydrogenolysis; sulfation; SO3 center dot triethylamine; bromotrimethylsilane; LACTAMASE; DEPROTECTION; ROUTE;

D O I：

10.1021/acs.oprd.1c00149

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The development of a robust manufacturing process to relebactam, a potent beta-lactamase inhibitor, is described. The origin and control strategy of oligomer impurities formed during hydrogenolysis of benzyl urea intermediate 9 and deprotection of Boc-sulfate intermediate 11 have been thoroughly studied and developed. The optimal manufacturing process has been successfully implemented for commercialization, preparing relebactam (1) in >99% purity with a non-detectable level of oligomers.

引用

页码：2249 / 2259

页数：11

共 50 条

[1] ORGN 815-Understanding the formation and control of impurities in process development of Reyataz
Yang, Ming Z.
Lotz, Bruce T.
Singh, Janak
Kissick, Thomas P.
Srivastava, Sushil K.
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232
[2] A PHASE APPROPRIATE APPROACH TO RP-HPLC METHOD DEVELOPMENT FOR IMPURITIES ANALYSIS IN ACTIVE PHARMACEUTICAL INGREDIENTS VIA CONTINUOUS MANUFACTURING PROCESS UNDERSTANDING
Yang, Shawn
Li, Yan
Chen, Ted K.
Kord, Alireza S.
[J]. JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES, 2011, 34 (01) : 61 - 82
[3] Development of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge
Santandrea, Ernesto
Waldraff, Christine
Gerber, Gilles
Moreau, Mael
Beney, Pascal
[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2021, 25 (05) : 1190 - 1205
[4] Analytical control of genotoxic impurities in the pazopanib hydrochloride manufacturing process
Liu, David Q.
Chen, Ted K.
McGuire, Michael A.
Kord, Alireza S.
[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2009, 50 (02) : 144 - 150
[5] Systematic and phase appropriate approach to RP-HPLC method development for impurities analysis in active pharmaceutical ingredients via continuous manufacturing process understanding
Yang, Shawn
Li, Yan
Chen, Ted
Kord, Alireza
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2010, 240
[6] Improve the efficiency of the inspection process via a thorough control of the scanning focus
Villa, Ernesto
Sartelli, Luca
Miyashita, Hiroyuki
[J]. PHOTOMASK TECHNOLOGY 2011, 2011, 8166
[7] Application of Quality by Design Principles to Support Development of a Control Strategy for the Control of Genotoxic Impurities in the Manufacturing Process of a Drug Substance
Cimarosti, Zadeo
Bravo, Fernando
Stonestreet, Paul
Tinazzi, Francesco
Vecchi, Orsola
Camurri, Giulio
[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2010, 14 (04) : 993 - 998
[8] From process understanding to control by PAT in tablet manufacturing
Bjorn, I. Niklasson
Folestad, S.
Luukkonen, P.
Karlsson, C.
[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY, 2005, 57 : S117 - S117
[9] Industrial Web inspection for manufacturing process understanding and control
Xu, WY
Floeder, SP
[J]. MACHINE VISION APPLICATIONS IN INDUSTRIAL INSPECTION VII, 1999, 3652 : 10 - 20
[10] Process modeling and control in drug development and manufacturing
Garcia Munoz, Salvador
Oksanen, Cynthia A.
[J]. COMPUTERS & CHEMICAL ENGINEERING, 2010, 34 (07) : 1007 - 1008

← 1 2 3 4 5 →