The Synthetic Routes of N-Cyclopropyl-5-fluoro-2-pyrimidinamine

N-Cyclopropyl-5-fluoro-2-pyrimidinamine is an important intermediate in the synthesis of several drugs, such as the antifungal drug Lariam and the antimalarial drug Coartem.
As such, there are several synthetic routes that have been developed in the chemical industry for the production of N-cyclopropyl-5-fluoro-2-pyrimidinamine.

One of the most common synthetic routes for N-cyclopropyl-5-fluoro-2-pyrimidinamine involves the reaction of cyclopropyl chloride with 5-fluoro-2-pyrimidine in the presence of a base, such as sodium hydroxide.
The reaction results in the formation of N-cyclopropyl-5-fluoro-2-pyrimidinamine, along with the corresponding alcohol and hydrochloric acid.

Another synthetic route involves the reaction of 5-fluoro-2-pyrimidine with cyclopropylamine in the presence of a strong acid, such as hydrochloric acid.
The reaction results in the formation of N-cyclopropyl-5-fluoro-2-pyrimidinamine, along with the corresponding carboxylic acid.
This route is less common than the first one, but it can be useful in some particular cases.

A third synthetic route involves the reaction of 5-fluoro-2-(aminomethyl)pyrimidine with cyclopropyl chloride in the presence of a phase transfer catalyst, such as benzotriazole.
The reaction results in the formation of N-cyclopropyl-5-fluoro-2-pyrimidinamine, along with the corresponding alcohol and hydrochloric acid.
This route is less common than the first two, but it has been reported in the literature.

All these synthetic routes have some advantages and disadvantages, depending on the specific conditions and reagents used.
For example, the first route is relatively simple and straightforward, but it requires the use of a strong base, which can be expensive and difficult to handle.
The second route is more economical, as it does not require the use of a strong base, but it requires the use of a strong acid, which can be hazardous and difficult to handle.
The third route is also relatively simple and straightforward, and it does not require the use of a strong base or acid, but it requires the use of a phase transfer catalyst, which can be expensive and difficult to handle.

Overall, N-cyclopropyl-5-fluoro-2-pyrimidinamine is an important intermediate in the synthesis of several drugs and there are several synthetic routes that have been developed in the chemical industry for its production.
The most common routes involve the reaction of cyclopropyl chloride with 5-fluoro-2-pyrimidine in the presence of a base, or the reaction of 5-fluoro-2-pyrimidine with cyclopropylamine in the presence of a strong acid.
These routes are relatively simple and straightforward, but they require the use of reagents that can be expensive and difficult to handle.
Therefore, it is important to consider the specific conditions and reagents used in each route before deciding which one to use.