PROCESS FOR PEMETREXED DISODIUM

摘要

The present invention provides a process for the preparation of N-[4-[2-(2-amino-4, 7 -dihydro-4-oxo-1 H-pyrrolo[2,3-d]pyrimidin-5-yl) ethyf]benzoyl]-L-glutamic acid dimethyl ester1 or salts thereof. The present invention also provides a process for the preparation of pemetrexed disodium substantially free of enatiomeric impurity. In another aspect, the present invention provides a process for the preparation of pemetrexed disodium substantially free of enantiomeric impurity, which comprises: a) stirring a solution of N-[4-[2-(2-amino-4,7-dihydro-4-oxo-IH-pyrrolo[2,3- d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid dimethyl ester 4- methylbenzenesulfonic acid with a mixture of sodium hydroxide and water at below 30°C; b) adjusting the pH of the reaction mass to above 7.2 with an acid; c) adding an organic solvent to the solution obtained in step (b) at below 30°C; and d) isolating the pemetrexed disodium substantially free of enantiomeric impurity.