The Synthetic Routes of 4-Amino-6-bromo-2-(trifluoromethyl)quinoline-3-carbonitrile

The Synthetic Routes of 4-Amino-6-bromo-2-(trifluoromethyl)quinoline-3-carbonitrile: An Overview in Chemical Industry

4-Amino-6-bromo-2-(trifluoromethyl)quinoline-3-carbonitrile, commonly referred to as BBR3152, is an important compound in the pharmaceutical industry.
It is a potent and selective inhibitor of pyruvate kinase, an enzyme that plays a critical role in energy metabolism.
The compound has shown promise as a potential treatment for a variety of diseases, including cancer, inflammation, and fibrosis.

The synthesis of BBR3152 is a complex process that involves multiple steps and several different chemical reactions.
The synthetic routes of BBR3152 can be broadly classified into two categories: traditional synthetic routes and newer synthetic routes.
In this article, we will provide an overview of the traditional and newer synthetic routes of BBR3152 and discuss their advantages and limitations.

Traditional Synthetic Routes

The traditional synthetic routes of BBR3152 involve several different chemical reactions, including halogenation, nitration, substitution, condensation, and reduction.
These routes require the use of hazardous reagents and require careful handling and purification of the intermediates.

One of the traditional synthetic routes of BBR3152 involves the halogenation of 4-amino-6-bromoquinoline-3-carbonitrile with N-bromosuccinimide (NBS) in the presence of a solvent such as dichloromethane.
This is followed by nitration of the resulting intermediate with nitric acid in the presence of a solvent such as acetonitrile.
The nitrated intermediate is then hydrolyzed with a strong acid such as sulfuric acid, and the resulting amine is condensed with benzaldehyde using a condensation agent such as dicyclohexylcarbodiimide (DCC).
The final step involves reduction of the resulting nitrobenzene with a reducing agent such as lithium aluminum hydride (LiAlH4).

Another traditional synthetic route involves the use of electrochemical methods to generate the nitro group.
This route requires the use of a nitrotransfer reagent such as nitrosonium tetrafluoroborate (NF4) and a strong acid such as sulfuric acid.
The resulting nitro group is then reduced using a reducing agent such as sodium borohydride (NaBH4).

Newer Synthetic Routes

In recent years, several newer synthetic routes of BBR3152 have been developed that involve fewer steps and less hazardous reagents.
One of these routes involves the use of a palladium-catalyzed cross-coupling reaction between 4-amino-6-bromoquinoline-3-carbonitrile and 2-bromo-3-trifluoromethyl-3H-pyrrole-1-carboxaldehyde in the presence of a ligand such as tetrakis(triphenylphosphine)palladium(0) and a solvent such as toluene.
This is followed by nitration of the resulting intermediate with nitric acid in the presence of a solvent such as acetonitrile, and the final step involves reduction of the resulting nitrobenzene with a reducing agent such as lithium aluminum hydride (LiAlH4).

Another newer synthetic route involves the use of a copper-catalyzed azide-alkyne cycloaddition reaction between 4-amino-6-bromoquinoline-3-carbonitrile and a nitrile such as