Process for the production of pemetrexed disodium

摘要

A manufacturing process of a pemetrexed disodium comprising: a) reacting a compound of formula II ** Formula ** or an acid salt thereof, wherein each of R1 and R2 is independently a C1-C6 alkyl group , with sodium hydroxide solution at a temperature not exceeding 10 ° C to obtain a first mixture; b1) add an organic anti-solvent to the first mixture of step a) to form a second mixture; b2) adjust the pH of the second mixture in a range of about 6.5 to about 9.5 to form a third mixture; b3) separate the pemetrexed disodium from the third mixture.