The Synthetic Routes of 5,7-dichlorothiazolo[4,5-d]pyriMidine

The synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine, a well-known antimalarial drug, has been a subject of extensive research in the chemical industry.
There are various synthetic routes that have been developed to synthesize this compound, each with its own advantages and limitations.
In this article, we will discuss some of the most commonly used synthetic routes for the synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine.

One of the most popular synthetic routes for the synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine is through the chlorination of 5,6-dichloro-4-[N-(4,5-dimethylthiazol-2-yl)-N-methylamino]pyrimidine (1).
This reaction involves the chlorination of pyrimidine ring of the parent compound by using phosphorus trichloride or thionyl chloride in the presence of a solvent such as dichloromethane or chloroform (Eq.
1).

Next, the product from the above reaction is treated with a reducing agent such as hydrogen in the presence of a catalyst like palladium on barium carbonate to reduce the nitro group to an amino group (Eq.
2).

The resulting product is then treated with a sulfurizing agent such as sulfuric acid in the presence of a solvent like dichloromethane.
This reaction leads to the formation of a sulfonamide group (Eq.
3).

Finally, the sulfonamide group is acylated by using a reagent like chloroformic acid in the presence of a solvent like dichloromethane (Eq.
4).

Another commonly used synthetic route for the synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine involves the starting material 2,4-dichloropyrimidine-5-carboxylic acid (5).
This route involves several steps, including the reaction of the starting material with a Grignard reagent, followed by treatment with an aqueous solution of sodium hydroxide and then with a sulfonation reagent like oleum.
The resulting product is then treated with phosphorus trichloride to introduce the thiazole ring (Eq.
5).

Another synthetic route for the synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine involves the reduction of 2,4-dichloropyrimidine-5-carboxylic acid (5) to form the corresponding aldehyde, which is then transformed into the corresponding nitrile by using a reagent like cyanogen bromide.
This nitrile is then treated with a thiourea derivative in the presence of a solvent like ethanol to introduce the thiazole ring.
Finally, the nitrile is reduced to the corresponding amide by using a reducing agent like lithium aluminum hydride (Eq.
6).

In conclusion, there are several synthetic routes for the synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine, each with its own advantages and limitations.
These routes involve several steps and require the use of various reagents and solvents.
The choice of route depends on the availability of starting materials, the desired yield, and the cost of the reaction.
The synthetic routes discussed in this article are just a few examples of the many synthetic methods that have been developed for the synthesis of 5,7-dichlorothiazolo[4,5-d]pyrimidine.