The Synthetic Routes of 1-[5-(Trifluoromethyl)pyridin-2-yl]piperazine

The synthesis of 1-[5-(Trifluoromethyl)pyridin-2-yl]piperazine, also known as 2-[(1S)-1-(5-trifluoromethyl-2-oxo-1,2-oxazolidin-3-yl)ethyl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine, is an important synthetic target in the field of medicinal chemistry due to its potential as a pharmaceutical agent.
There are various synthetic routes have been reported in the literature for the preparation of this compound, which can be broadly classified into three categories: direct synthesis, indirect synthesis, and semi-synthesis.

Direct Synthesis:
Direct synthesis refers to the synthesis of the target compound by a consecutive series of reactions in which the final product is obtained without any isolation or purification steps.
This approach is often challenging and requires a high level of synthetic expertise.

One of the most popular direct synthesis routes for the preparation of 1-[5-(Trifluoromethyl)pyridin-2-yl]piperazine is the "one-pot" reaction.
This synthesis involves the condensation of 2-chloro-5-[(dihydroimidazo[1,2-d][1,4]benzoxazepin-3-yl)amino]pyridine with 1-[(2-hydroxy-1,3-oxazolidin-3-yl)amino]-4-fluoro-7-(2,6-difluoro-4-oxo-3,4-dihydroquinazolin-3-yl)pyrrole in the presence of a catalyst, such as HATU, and a base like DIEA.
This reaction results in the formation of the desired compound in a single step with a moderate yield.
However, this route is highly dependent on the availability of the starting materials and the reaction conditions.

Indirect Synthesis:
Indirect synthesis refers to the synthesis of the target compound by a series of intermediate steps, followed by the isolation and purification of the intermediate or the final product.
This approach is more flexible and allows for the optimization of individual steps.

One of the most popular indirect synthesis routes for the preparation of 1-[5-(Trifluoromethyl)pyridin-2-yl]piperazine is the "classical" synthesis.
This synthesis involves the synthesis of the intermediate 2-[(1S)-1-(5-trifluoromethyl-2-oxo-1,2-oxazolidin-3-yl)ethyl]-5,6-dihydroim