The Production Process of 5-(((2S,3S)-2-((S)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholino)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one: A Comprehensive Overview

In the field of chemistry, the process of producing a new drug or chemical compound is a complex and multi-step process.
Each compound requires a unique set of synthetic methods and conditions to produce it efficiently and cost-effectively.
One such compound is 5-(((2S,3S)-2-((S)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(4-fluorophenyl)morpholino)methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one, which is commonly referred to as NV-028.
This article provides a comprehensive overview of the production process of NV-028, including the starting materials, synthetic methods, purification, and isolation steps.

Starting Materials

The synthesis of NV-028 involves several starting materials, including (S)-1-(3,5-bis(trifluoromethyl)phenyl)ethanone, 4-fluoro-3-nitrophenyl morpholine, and 2,4-dihydro-3H-1,2,4-triazol-3-one.
The first starting material, (S)-1-(3,5-bis(trifluoromethyl)phenyl)ethanone, is synthesized from readily available starting materials such as 3,5-bis(trifluoromethyl)phenylamine and ethyl bromide.
The second starting material, 4-fluoro-3-nitrophenyl morpholine, is prepared by known methods, such as the Bischler-Napieralski reaction.
The third starting material, 2,4-dihydro-3H-1,2,4-triazol-3-one, is also easily accessible through known synthetic routes.

Synthetic Methods

The synthesis of NV-028 involves several steps, including condensation, reduction, and nitration reactions.
The synthesis of NV-028 can be summarized as follows:

1. Condensation of (S)-1-(3,5-bis(trifluoromethyl)phenyl)ethanone and 4-fluoro-3-nitrophenyl morpholine in the presence of a base such as sodium hydroxide to form a biphenylamine intermediate.
   
2. Reduction of the biphenylamine intermediate to form an amine intermediate using a reducing agent such as lithium aluminum hydride.
   
3. Nitration of the amine intermediate with nitric acid to introduce the nitro group.
   
4. Condensation of the nitrated amine with 2,4-dihydro-3H-1,2,4-triazol-3-one in the presence of a condensation agent such as dicyclohexylcarbodiimide to form the final product, NV-028.
   

Purification and Isolation

After the synthesis of NV-028, the crude product is typically purified using chromatography techniques, such as high-performance liquid chromatography (HPLC) or column chromatography.
These techniques involve separating the desired product from the unwanted side products and impurities based on their physical and chemical properties.

For example, HPLC can be used to separate NV-028 from other compounds by optimizing the column conditions, such as the type of stationary phase and the mobile phase composition.
In addition, HPLC can be coupled with mass spectrometry (MS) to detect and identify the individual components in the sample.

Alternatively, column chromatography can