The Production Process of Imatinib (Pyridine)-N-oxide

Imatinib (Pyridine)-N-oxide, also known as STI571, is a cancer medication that is primarily used to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs).
The production process of imatinib (Pyridine)-N-oxide involves several steps, from the preparation of the starting materials to the isolation and purification of the final product.

1. Preparation of starting materials

The production of imatinib (Pyridine)-N-oxide starts with the preparation of the starting materials, which include pyridine-2,6-dicarboxylic acid and 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzamide.
Pyridine-2,6-dicarboxylic acid is prepared by a series of chemical reactions, including the reaction of 2,6-dimethylanthrahydroquinone with chloroform and subsequent treatment with a strong acid.
2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzamide is prepared by a similar process, involving the reaction of 2-chloro-4-(2-nitrophenyl)benzamide with 1-methyl-1H-pyrazole.

1. Condensation reaction

The next step in the production of imatinib (Pyridine)-N-oxide is the condensation reaction, which involves the reaction of pyridine-2,6-dicarboxylic acid and 2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzamide in the presence of a condensing agent, such as dicyclohexylcarbodiimide (DCC).
The condensation reaction results in the formation of a mixture of imatinib (Pyridine)-N-oxide isomers, which are then separated and purified.

1. Purification of the isomers

The isomers of imatinib (Pyridine)-N-oxide are separated and purified using a combination of chromatography techniques, including high-performance liquid chromatography (HPLC) andcolumns.
The purified isomers are then further characterized using techniques such as nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry.

1. Isolation of the desired isomer

After the purification of the isomers, the desired isomer of imatinib (Pyridine)-N-oxide is isolated using a process known as chiral chromatography.
This process uses a chiral stationary phase to separate the enantiomers of the isomers and to isolate the desired enantiomer.

1. Crystallization

The final step in the production of imatinib (Pyridine)-N-oxide is the crystallization of the purified and isolated isomer.
This is done by dissolving the isomer in a suitable solvent and allowing it to crystallize out.
The crystals are then collected and dried, and their structure is confirmed using X-ray crystallography.

In conclusion, the production of imatinib (Pyridine)-N-oxide involves several steps, from the preparation of the starting materials to the isolation and purification of the final product.
The process requires the use of advanced chromatography and purification techniques, as well as the isolation of the desired isomer using chiral chromatography.
The crystallization of the purified isomer is the final step in the production process, and it confirms the identity and structure of the final product.