The Synthetic Routes of Amlodipine

Amlodipine is a widely used medication for treating hypertension and angina pectoris.
It is a dihydropyridine calcium channel blocker, which works by relaxing the smooth muscle in the blood vessels, leading to dilation and decrease in blood pressure.
The synthetic route of amlodipine has undergone several changes over the years, with the objective of producing the drug in a more efficient and cost-effective manner.
In this article, we will discuss the various synthetic routes of amlodipine and their underlying principles.

One of the early synthetic routes of amlodipine involved the reaction of 2-chloro-5-nitro-aniline with 3-dimethylaminomethyl-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine, followed by oxidation of the resultant intermediate.
This route involved several steps, including nitration, diazotization, coupling, and oxidation, and required the use of hazardous reagents such as nitric acid and hydrogen peroxide.

A more recent and efficient synthetic route for amlodipine involves the reaction of 2-(ethoxycarbonyl)amino-5-methyl-1,3-oxazolidin-3-one with chloroformic acid in the presence of a base such as sodium carbonate.
This route involves only three steps, eliminating the need for hazardous reagents and reducing the overall cost of production.

Another synthetic route for amlodipine involves the reaction of 5-methyl-2-(2'-nitrophenylamino)tetrazole with 2,2'-dipyranoylmethylphosphonate, followed by hydrolysis of the resultant intermediate.
This route is also efficient and involves only three steps.

Amlodipine can also be synthesized by a multi-step synthesis involving the reaction of 2-chloro-5-nitroaniline with 3,5-dimethoxy-4-methylbenzaldehyde, followed by nitration, diazo coupling, and hydrolysis.
This route is less commonly used due to the use of hazardous reagents and the complexity of the synthesis.

In conclusion, there are several synthetic routes for amlodipine, each with its unique set of advantages and disadvantages.
The choice of synthetic route depends on various factors such as the availability of reagents, the cost of production, and the hazardous nature of the reagents.
Regardless of the synthetic route, amlodipine remains an important medication for treating hypertension and angina pectoris, and its synthesis continues to evolve to meet the demands of the pharmaceutical industry.