SINGLE-VESSEL METHOD OF PRODUCING PEMETREXED DISODIUM Russian patent published in 2016 - IPC C07D487/04 

FIELD: chemistry.

SUBSTANCE: invention relates to the improved method of producing pemetrexed disodium 2,5-hydrate, which exhibits antifolate activity and can be used to treat different types of cancer. The method includes a. suspending N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid of a di-lower alkyl ester of a sulphonic acid salt in an aqueous solution containing NaOH; b. desalination and hydrolysis thereof by mixing the mixture to obtain a solution; c. salting out pemetrexed disodium with a water-soluble sodium salt after bringing the temperature to room temperature and bringing the pH of the obtained mixture to 7-9; and d. separating pemetrexed disodium 2,5-hydrate from the mixture by filtering and then drying. N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid of diethyl ester of p-toluenesulphonic acid is primarily used. Hydrolysis is normally carried out in the presence of 3-6 sodium hydroxide equivalents at 0-75°C, preferably at 0-5°C.

EFFECT: method enables to obtain a product in the form of a pure medicinal substance in one vessel without using solvents.

5 cl, 2 ex