New, Scalable Process for the Preparation of 5-Acetyl-1H-pyrazole-3-carboxylic Acid, a Key Intermediate of Darolutamide

Poszávácz, László; Nagy, Tamás; Kátai-Fadgyas, Katalin; Volk, Balázs

doi:10.1055/a-2016-4337

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…In continuation of our efforts aiming at the technological − and analytical , development of drug substance manufacturing processes, we also tried to achieve economical improvements in the synthetic procedure leading to levomepromazine [( R )- 1 ]. In order to obtain recovered 2-methoxyphenothiazine ( 2 ) in a reasonable yield and required purity, we aimed to transform the one-pot procedure (see above, Scheme ) into an easily scalable process by isolating and purifying certain intermediates.…”

Section: Resultsmentioning

confidence: 99%

Points of Interest in the Chemistry of the Levomepromazine Drug Substance: Recycling of Undesired Enantiomer, Identification of New Phenothiazine Dimers, Synthesis of a Pharmacopeial Impurity, and an Unexpected Rearrangement

Poszávácz,

Porcs-Makkay,

Halász

et al. 2024

Org. Process Res. Dev.

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As a traditional manufacturer of drug substance levomepromazine maleate, we were interested in the elaboration of an optimized process that uses the undesired enantiomer dextromepromazine, a waste product from the production of levomepromazine, to recover the starting material 2-methoxyphenothiazine. In 2-methoxyphenothiazine samples, two new dimertype impurities have been detected and these have also been synthesized. One of these dimers was used for the preparation of the pharmacopeial standard Imp. D, on the synthesis and characterization of which the literature is surprisingly silent. During the attempted synthesis of another pharmacopeial impurity (Imp. E), similarly unknown in the literature, an unexpected rearrangement was discovered. Its possible mechanism is also discussed below.

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Section: Resultsmentioning

confidence: 99%

Points of Interest in the Chemistry of the Levomepromazine Drug Substance: Recycling of Undesired Enantiomer, Identification of New Phenothiazine Dimers, Synthesis of a Pharmacopeial Impurity, and an Unexpected Rearrangement

Poszávácz,

Porcs-Makkay,

Halász

et al. 2024

Org. Process Res. Dev.

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Modern Approaches to the Synthesis of Pyrazoles (A Review)

Baeva,

Gataullin

2024

Žurnal obŝej himii

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The article analyzes publications that present the results of studies of modern approaches to the synthesis of new and known heterocycles with a pyrazole fragment, as well as syntheses aimed at expanding the library of compounds of this series from hydrazines, hydrazides, semi- or thiosemicarbazides, diazo compounds, hydrazonyl chlorides. Some examples are shown that use approaches to the synthesis of pyrazoles through multicomponent reactions involving amines and hydroxamic acid or an amine and enaminoketone. References are provided to publications that reflect the results of studies of the biological activity of these heterocycles, the use of certain metals as selective extractants, the possibility of obtaining metal complexes with their participation, as well as some photochemical transformations.

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New, Scalable Process for the Preparation of 5-Acetyl-1H-pyrazole-3-carboxylic Acid, a Key Intermediate of Darolutamide

Cited by 2 publications

References 16 publications

Points of Interest in the Chemistry of the Levomepromazine Drug Substance: Recycling of Undesired Enantiomer, Identification of New Phenothiazine Dimers, Synthesis of a Pharmacopeial Impurity, and an Unexpected Rearrangement

Points of Interest in the Chemistry of the Levomepromazine Drug Substance: Recycling of Undesired Enantiomer, Identification of New Phenothiazine Dimers, Synthesis of a Pharmacopeial Impurity, and an Unexpected Rearrangement

Modern Approaches to the Synthesis of Pyrazoles (A Review)

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