The Synthetic Routes of Nintedanib esylate

Nintedanib esylate is a phosphatidylinositol 3-kinase (PI3K) inhibitor used in the treatment of various types of cancer.
It is an important drug in the treatment of cancer and has shown promise in the treatment of a variety of tumor types, including kidney, lung, and breast cancer.
The synthetic routes of Nintedanib esylate can be divided into several steps, which are explained below.

Step 1: Synthesis of the Phosphoramidite Building Block
The first step in the synthesis of Nintedanib esylate is the synthesis of the phosphoramidite building block.
This is done by reacting a phosphorus oxychloride with a diamine, followed by hydrolysis to form the corresponding phosphoramidite.
The phosphoramidite is then treated with a protected amino acid to form a phosphoramidate.

Step 2: Synthesis of the Cytosine building block
The next step in the synthesis of Nintedanib esylate is the synthesis of the cytosine building block.
This is done by reacting a cytosine precursor with a protected amino acid to form a cytosine thioethylester.
This thioethylester is then treated with a sulfurizing agent to form the final cytosine building block.

Step 3: Synthesis of the Pyrimidine building block
The final step in the synthesis of Nintedanib esylate is the synthesis of the pyrimidine building block.
This is done by reacting a pyrimidine precursor with a protected amino acid to form a pyrimidine thioethylester.
This thioethylester is then treated with a sulfurizing agent to form the final pyrimidine building block.

Step 4: Assembly of the Final Product
The final step in the synthesis of Nintedanib esylate is the assembly of the final product.
This is done by reacting the phosphoramidite building block, cytosine building block, and pyrimidine building block to form the final product.
The reaction is typically carried out in the presence of a nucleophile, such as water or an organic solvent, and is often catalyzed by a Lewis acid or a transition metal catalyst.
The final product is then purified by standard techniques, such as chromatography or crystallization, to remove any impurities.

Overall, the synthetic routes of Nintedanib esylate involve several steps, including the synthesis of the phosphoramidite building block, cytosine building block, and pyrimidine building block, and the assembly of these building blocks to form the final product.
These steps are carried out using standard synthetic methods and can be modified as needed to optimize the synthesis of this important drug.