In:
Letters in Organic Chemistry, Bentham Science Publishers Ltd., Vol. 19, No. 6 ( 2022-06), p. 484-489
Kurzfassung:
Photochemical decomposition of lomefloxacin (Lom) is supposed to result
in the generation of C-8 substituted impurity and accompanied fluoride. The existence and amount of C-8 hydroxyl substituted Lom could be proposed as the marker to the stability and
process consistency. The specific C-8 hydroxyl substituent impurity (1-ethyl-6-fluoro-8- hydroxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid) was designed
and synthesized to be available. Method: 2,4,5-trifluoro-3-methoxybenzoic acid as the initial reactant was subjected to a series
of seven-step reactions, such as acylation, condensation with trans N,N-dimethylamino ethyl acrylate, N-ethylation, cyclization, hydrolysis, condensation with piperazine and acidification.
The resultant substance was then purified using HPLC and C18 solid-phase extraction. The structure of C-8 hydroxyl substituted Lom was identified with 1H-NMR, 13C-NMR and HRMS
spectroscopes, as well as the purity was determined by HPLC. Conclusion: C-8 hydroxyl substituted Lom was successfully synthesized and purified with purity
more than 96%. This photolysis impurity offers an alternative for not only further generic Lom active pharmaceutical ingredient development involved in quality control and consistency
evaluation, but also research for the mechanism underlying Lom-induced photosensitivity.
Materialart:
Online-Ressource
ISSN:
1570-1786
DOI:
10.2174/1570178618666210914125620
Sprache:
Englisch
Verlag:
Bentham Science Publishers Ltd.
Publikationsdatum:
2022
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