The Synthetic Routes of Agomelatine

Introduction:

Agomelatine is a synthetic compound that is used as an antidepressant medication.
It is primarily used to treat major depressive disorder and bipolar disorder.
This article will discuss the synthetic routes of agomelatine and the various methods used to synthesize this compound.

Synthetic Routes:

There are several synthetic routes that can be used to synthesize agomelatine.
Some of the most common methods are outlined below:

1. The Hydrogenation of N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide:

This is the most common synthetic route for agomelatine.
It involves the hydrogenation of N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide.
This intermediate is then cyclized under acidic conditions to yield agomelatine.

2. The Reduction of 2-(2,3-dihydro-1H-inden-4-ylamino)-N-(2-methoxyethyl) acetamide:

This route involves the reduction of 2-(2,3-dihydro-1H-inden-4-ylamino)-N-(2-methoxyethyl) acetamide using hydrogen in the presence of a metal catalyst.
This reaction leads to the formation of agomelatine.

3. The Decarboxylation of N-(2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl) acetamide:

This route involves the decarboxylation of N-(2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl) acetamide in the presence of a strong acid.
This reaction leads to the formation of agomelatine.

Synthesis of Key Intermediate: N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide:

The synthesis of N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide is a key step in the synthesis of agomelatine.
This intermediate can be synthesized using several methods, including the following:

1. From 2,3-dihydro-1H-inden-2-amine and N-methyl acetamide:

This synthesis involves the reaction of 2,3-dihydro-1H-inden-2-amine and N-methyl acetamide in the presence of a base, such as sodium hydride.
The reaction leads to the formation of N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide, which can be hydrogenated to yield agomelatine.

2. From 2,3-dihydro-1H-inden-4-amine and N-methyl acetamide:

This synthesis involves the reaction of 2,3-dihydro-1H-inden-4-amine and N-methyl acetamide in the presence of a strong acid, such as sulfuric acid.
The reaction leads to the formation of N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide, which can be hydrogenated to yield agomelatine.

Conclusion:

Agomelatine is a synthetic compound that is used as an antidepressant medication.
There are several synthetic routes that can be used to synthesize agomelatine, with the most common methods involving the hydrogenation of N-Bromo-2-(2,3-dihydro-1H-inden-4-ylamino)-N-methyl acetamide or the reduction of 2-(2,3-dihydro-1H-inden-4-