The Synthetic Routes of Bosutinib

Bosutinib is a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia and other cancers.
Its synthesis has been reported in several literature, but the most commonly reported synthetic route is through a three-step sequence starting from salicylaldehyde.

The first step in the synthesis of bosutinib is the preparation of N-Boc-salicylaldehyde, which is achieved by the reaction of salicylaldehyde with excess of di-tert-butyl dicarbonate in the presence of a catalytic amount of triethylamine.
The reaction is followed by gentle hydrolysis of the obtained N-Boc-salicylaldehyde in aqueous sodium hydroxide and the resulting N-Boc-salicylaldehyde is then reduced with lithium aluminum hydride to obtain N-Boc-salicyl alcohol.

The next step in the synthesis of bosutinib is the preparation of N-Boc-L-prolinamide, which is obtained by reacting N-Boc-salicyl alcohol with L-proline in the presence of a strong base such as sodium hydride.
The reaction is then followed by treatment with hydrochloric acid to remove the Boc protecting group, yielding N-L-prolinamide.

The final step in the synthesis of bosutinib is the reaction of N-L-prolinamide with a commercially available aryl bromide in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0) and the resulting N-L-prolinamide is then converted to N-L-prolinamide hydrate by treating with water.
The hydrate is then reduced with lithium aluminum hydride to obtain N-L-prolinamide, which is then treated with a solution of hydrogen chloride in 1,4-dioxane to remove the N-Boc protecting group and obtain bosutinib.

Other synthetic routes to bosutinib have been reported in the literature, but the above-described route is considered to be the most practical and efficient one.
The synthesis of bosutinib requires the use of various reagents and equipment and it is important to follow proper safety procedures to avoid any hazards.

Overall, the synthesis of bosutinib is a complex multi-step process that requires the use of various reagents and equipment, but it is an important drug for the treatment of cancer.
It is important that the synthesis is performed by trained personnel in a well-equipped laboratory, and that proper safety procedures are followed to avoid any hazards.