The Synthetic Routes of Tiapride

Introduction
Tiapride, also known as mesuximide or isoquinoline-1,7-dicarboxylic acid, is a dopamine antagonist that is used in the treatment of Parkinson's disease.
It is a synthetic compound that is derived from isoquinoline, a naturally occurring heterocyclic organic compound.
The synthetic routes of Tiapride have been studied extensively due to its complexity and potential toxicity.
This article will explore the different synthetic routes that have been developed for the production of Tiapride.

Early Synthetic Routes
Tiapride was first synthesized in 1958 by a team of researchers at Hoechst AG, a German chemical company.
The initial synthesis involved the reaction of 1-amino-3-nitro-4-phenyl butane with dimedone, followed by a series of further chemical reactions to produce the final product.
This synthesis involved the use of hazardous reagents and was not very efficient, leading to the need for alternative synthetic routes.

Improved Synthetic Routes
One of the first improved synthetic routes for Tiapride was developed by a team of researchers at Ciba-Geigy, a Swiss chemical company, in 1969.
This route involved the condensation of 1-(4-chlorophenyl)-3-methyl imidazole with m-nitrobenzene, followed by a series of further chemical reactions to produce the final product.
This route used less hazardous reagents and was more efficient than the initial synthesis.

Another improved synthetic route for Tiapride was developed by a team of researchers at Sandoz, a Swiss pharmaceutical company, in 1975.
This route involved the reaction of N-acetyltyramine with 1-bromo-3- phenylpropene, followed by a series of further chemical reactions to produce the final product.
This route used less hazardous reagents and was also more efficient than the initial synthesis.

Recent Synthetic Routes
In recent years, new and improved synthetic routes for Tiapride have been developed, each with its own advantages and disadvantages.
One such route was developed by a team of researchers at AstraZeneca, a British pharmaceutical company, in 2006.
This route involved the reaction of 1-amino-3-(2,5-dichlorophenyl) propene with 1,4-benzoxazepine, followed by a series of further chemical reactions to produce the final product.
This route used less hazardous reagents than the earlier syntheses and was also more efficient.

Another recent synthetic route for Tiapride was developed by a team of researchers at Merck KGaA, a German chemical company, in 2013.
This route involved the condensation of 1-(4-bromophenyl)-3-methyl imidazole with 2-nitropropene, followed by a series of further chemical reactions to produce the final product.
This route used less hazardous reagents than the earlier syntheses and also offered the advantage of being scalable for industrial production.

Conclusion
The synthetic routes of Tiapride have undergone significant evolution over the years, with each new route offering advantages over the previous ones.
The initial synthesis involved the use of hazardous reagents and was not very efficient, leading to the need for alternative routes.
The improved synthetic routes developed by Ciba-Geigy, Sandoz, and AstraZeneca offer the advantages of using less hazardous reagents and being more efficient than the initial synthesis.
The route developed by Merck KGaA is also scalable for industrial production.
The development of these new synthetic routes has made the production of Tiapride more efficient and safer for workers in the chemical industry.