The Synthetic Routes of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile

The synthesis of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile, a commonly used intermediate in the chemical industry, can be achieved through several synthetic routes.
This article will discuss three commonly used synthetic routes for the synthesis of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile, which are the literature synthetic route, the optimized synthetic route, and the one-pot synthetic route.

Literature Synthetic Route

The literature synthetic route for the synthesis of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile involves several steps, including the synthesis of 2-pyrimidinamine, the condensation of 2-pyrimidinamine with malononitrile, and the Williamson ether synthesis of 4-chloro-1-(pyrimidin-2-yl)-1H-pyrazole-3-carbonitrile.
This route involves the use of several reagents and is shown in Scheme 1 below.

Scheme 1: Literature Synthetic Route for the Synthesis of 5-Fluoro-1-(Pyrimidin-2-Yl)-1H-Pyrazole-4-Carbonitrile

Optimized Synthetic Route

The optimized synthetic route for the synthesis of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile involves the use of a modified synthetic route, which is shown in Scheme 2 below.

Scheme 2: Optimized Synthetic Route for the Synthesis of 5-Fluoro-1-(Pyrimidin-2-Yl)-1H-Pyrazole-4-Carbonitrile

One-Pot Synthetic Route

The one-pot synthetic route for the synthesis of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile involves a single-step synthesis that involves the use of HATU as a condensing agent and DIPEA as a base, which is shown in Scheme 3 below.

Scheme 3: One-Pot Synthetic Route for the Synthesis of 5-Fluoro-1-(Pyrimidin-2-Yl)-1H-Pyrazole-4-Carbonitrile

Advantages of the One-Pot Synthetic Route

The one-pot synthetic route has several advantages over the literature and optimized synthetic routes.
Firstly, it involves a single-step synthesis, which reduces the time and complexity of the synthesis.
Secondly, it involves the use of relatively inexpensive and easily available reagents, which reduces the cost of the synthesis.
Thirdly, the use of HATU and DIPEA as catalysts and base, respectively, eliminates the need for the separate addition of reagents, which reduces the risk of contamination and the likelihood of human error.
Finally, the use of a single-step synthesis eliminates the need for purification steps, which further simplifies the synthesis and reduces the overall time and cost of the synthesis.

Conclusion

The synthesis of 5-fluoro-1-(pyrimidin-2-yl)-1H-pyrazole-4-carbonitrile can be achieved through several synthetic routes, including the literature synthetic route, the optimized synthetic route, and the one-pot synthetic route.
The one-pot synthetic route has several advantages over the literature and optimized synthetic routes, including the use of a single-step synthesis, the use of relatively inexpensive and easily available reagents, the elimination of the need for purification steps,