The Production Process of Edoxaban tosylate

Edoxaban is an oral anticoagulant medication used to prevent blood clots in patients with non-valvular atrial fibrillation.
It is also used in the prevention of deep vein thrombosis and pulmonary embolism in adults.
The production process of Edoxaban tosylate involves several steps, which will be discussed in detail in this article.

Step 1: Synthesis of Edoxaban
The synthesis of Edoxaban involves several steps, including the preparation of the starting materials, the reaction steps, and the purification of the product.
The synthesis of Edoxaban typically begins with the preparation of the starting materials, which includes the reaction of 3-methyl-1,2,4-oxadiazole-5-carboxylic acid (MOC) and N-(2,4-dichlorophenyl)maleimide (DCPMI).
This reaction is typically carried out in the presence of a solvent, such as dichloromethane, and a base, such as pyridine.
The reaction produces the intermediate N-[(3S)-3-methyl-1,2,4-oxadiazole-5-carbonyl]-N-(2,4-dichlorophenyl)amide, which is then hydrolyzed to produce N-[(3S)-3-methyl-1,2,4-oxadiazole-5-carbonyl]-N-(2,4-dichlorophenyl)acetamide.

Step 2: Condensation of Edoxaban with Tosylate
The next step in the synthesis of Edoxaban is the condensation of N-[(3S)-3-methyl-1,2,4-oxadiazole-5-carbonyl]-N-(2,4-dichlorophenyl)acetamide with tosylate.
This reaction typically involves the use of a condensation agent, such as dicyclohexylcarbodiimide (DCC), hydroxybenzotriazole (HOBT), and N,N-diisopropylethylamine (DIEA), in the presence of a solvent, such as dimethylformamide (DMF).
The resulting product is then purified by column chromatography, using a mixture of ethyl acetate and methanol as the eluent.

Step 3: Hydrolysis of Edoxaban Tosylate
The Edoxaban tosylate produced in the previous step is then subjected to hydrolysis, which involves the removal of the tosylate group.
This is typically carried out using a strong acid, such as hydrochloric acid, in the presence of a solvent, such as ethyl acetate.
The resulting product is then purified by column chromatography, using a mixture of ethyl acetate and methanol as the eluent.

Step 4: Purification of Edoxaban
The final step in the production process of Edoxaban is the purification of the product.
This typically involves several steps, including the removal of any remaining impurities using a mixture of ethyl acetate and methanol, and then recrystallization of the product using a suitable solvent, such as ethanol.
The resulting product is then dried and ground to produce a fine powder.

Quality Control
Quality control is an essential part of the production process of Edoxaban tosylate.
This involves testing the product at various stages of production to ensure that it meets the required specifications for purity, identity, and potency.
The tests may include:

1. Chromatography: This involves the separation of the product into its individual components, and determining their purity and identity.
   
2. Mass Spectrometry: This involves the determination of the molecular mass of the product, which is used to identify and quantify the components of the product.