Process Development and Synthesis of Process-Related Impurities of an Efficient Scale-Up Preparation of 5,2'-Dibromo-2,4',5'-Trihydroxy Diphenylmethanone as a New Acute Pyelonephritis Candidate Drug
Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone ( ), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profil...
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Published in | Molecules (Basel, Switzerland) Vol. 25; no. 3; p. 468 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
22.01.2020
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (
), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profiles. Meanwhile, the polymorph of
and process-related impurities were also investigated. Ultimately, the optimal reaction conditions were verified by evaluating the impurity profiles and their formation during the synthesis. Six process-related impurities were synthesized and identified, being useful for the quality control of
. Its finalized preparation process was further validated at 329-410 g scale-up production in 53.4-57.1% overall yield with 99.95-99.98% high-performance liquid chromatography (HPLC) purity, and it is currently viable for commercial production.
and
were identified as the main single impurities in
, with the content controlled to be less than 0.03%. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 1420-3049 1420-3049 |
DOI: | 10.3390/molecules25030468 |